A Case Report

A Rare Cause of Abdominal Pain in Plain Sight

January 2017 • Volume XLI, Issue 1
Jordan Orr,Basem Alkurdi

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Visceral angioedema, swelling of the soft tissues and organs of the abdominal cavity leading to signi cant gastrointestinal symptoms, is a rare adverse reaction associated with the use of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. While several cases of ACEI-induced visceral angioedema have been reported, only one case of ARB-induced visceral angioedema exists. We report a unique case of ARB-induced visceral angioedema from the use of irbesartan and discuss the management and clinical importance of visceral angioedema.

Jordan Orr, MD Basem Alkurdi, MD, The University of Alabama at Birmingham, AL

INTRODUCTION

Angioedema is the classic adverse drug reaction of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) that manifests as swelling of the face, tongue and lips and can be potentially life threatening. Even though universally recognized, this adverse reaction is rare with a defined incidence of 0.1% to 0.7% of patients taking an ACEI.1 An even less frequent manifestation of angioedema is visceral angioedema which is characterized by swelling of the soft tissues and organs of the abdominal cavity leading to significant gastrointestinal symptoms. Visceral angioedema is classically associated with ACE inhibitors however it is also rarely observed with the use of ARBs. Only 28 cases of ACEI induced visceral angioedema have been reported in literature from 1980-2010 and the reported cases of ARB induced visceral angioedema are even less frequent.1,2

Case Presentation

A 59-year-old female presented to the emergency department at a community hospital with complaints of severe cramping periumbilical abdominal pain with radiation to the lower abdomen. Her history was significant for diverticulitis, gastroesophageal reflux disease and multiple abdominal surgeries including Nissen fundoplication, cholecystectomy, hysterectomy, appendectomy and sigmoid resection for suspected ischemic colitis. Her pain was associated with bloating and severe nausea without vomiting. Computed tomography (CT) of the abdomen and pelvis was suggestive of small bowel obstruction with surrounding edema. She was admitted to the hospital and ultimately underwent exploratory laparotomy. Intraoperative findings revealed a normal small bowel without evidence of ischemia or adhesions. Serial CT scans throughout her hospitalization displayed successive resolving free fluid, small bowel wall thickening and stranding in the surrounding mesentery with resolution of findings by hospital day three (Figure 1, 2, 3). Without a diagnosis and symptomatically improved, she was discharged and referred to the gastroenterology clinic at our tertiary medical care center. She again presented with symptoms of abdominal pain and nausea, similar to her initial presentation despite normal vital signs, abdominal exam and laboratory work up. Review of her recent hospital course revealed her home medications, including irbesartan, had been held while hospitalized. This coincided with her resolving CT findings. Her irbesartan was discontinued and, at one-month follow up, she was asymptomatic, confirming the diagnosis of ARB induced visceral angioedema.

Discussion

Visceral angioedema is a rare cause of abdominal pain. The presenting gastrointestinal symptoms of visceral angioedema can be broad (abdominal pain, cramping, colicky pain, nausea, vomiting, diarrhea) and are often mistaken for a surgical abdomen.3 In fact, it is not uncommon for the patient presenting to the emergency department with visceral angioedema to undergo surgical exploration due to the degree of symptoms and radiologic findings.4 CT images of visceral angioedema classically display thickening, dilation and straightening of the small bowel with preservation of luminal transit.3 Other potential etiologies of these radiographic findings include small-bowel ischemia, superior mesenteric and portal vein thrombosis, radiation, vasculitidies, Crohn’s disease, hemorrhage, pneumatosis or ulceration, thus making the radiological diagnosis of visceral angioedema increasingly difficult.3 The pathogenesis of ACEI-induced angioedema is well described and felt to be due to the accumulation and potentiation of bradykinin, the molecule that evades degradation by angiotensin converting enzyme inhibition. This abnormal accumulation of bradykinin causes overwhelming vasodilation and increased permeability leading to the observed edema.1,2 The pathogenesis of ARB-induced visceral angioedema, however, is not well understood. It is conceivable that ARBs also lead to bradykinin accumulation by the feedback-induced increase in angiotensin II levels in plasma, however further investigation is needed to help explain the phenomenon of ARB induced angioedema.2 A high degree of suspicion is needed to diagnose visceral angioedema. Once recognized, the symptoms of visceral angioedema often resolve in as little as 48 hours if the offending medication is removed.1 Unfortunately, many patients suffer from prolonged symptoms from unrecognized visceral angioedema. One study reported a median of 10 months elapsed between onset of visceral angioedema and withdrawal of the ACEI, and many cases are reported of patients with visceral angioedema who took an ACEI for years before the cause of their symptoms was diagnosed.1 In patients who have experienced any degree of angioedema, clinicians should be careful about switching a patient from an ACEI to an ARB. Recurrent angioedema has been reported to occur in 1.5% to 10% of patients after changing medication classes. Recurrent visceral angioedema has also been reported after switching from an ACEI to an ARB.2 It is recommended that clinicians wait a period of four weeks after discontinuing an ACEI and starting an ARB so that residual ACEI induced angioedema is not mistaken for new ARB induced angioedema.2

This rare but important cause of abdominal pain can be easily overlooked without a careful review of the medication list however recognition of this process and discontinuation of the provoking medication will save the patient from unnecessary diagnostic evaluation and intervention and bring timely symptomatic relief.

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Inflammatory Bowel Disease: A Practical Approach, Series #100

Fecal Microbiota Transplantation for Recurrent or Refractory Clostridium difficile Infection in IBD

January 2017 • Volume XLI, Issue 1
Yao-Wen Cheng,Monika Fischer

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A recent multicenter study demonstrated safety and efficacy of fecal microbiota transplant (FMT) for the treatment of recurrent or refractory CDI in IBD patients with cure rates comparable to the general population. Here we discuss the impact of FMT on underlying IBD and its position in the treatment paradigm.

Over the past decade, the incidence of Clostridium difficile infection (CDI) has more than doubled. Fecal microbiota transplant (FMT) has emerged as a guideline-based treatment for recurrent and refractory disease. However, the role of FMT for the treatment of CDI in patients with underlying inflammatory bowel disease (IBD) is controversial despite higher CDI-related complication rates in this population including mortality, colectomy, and recurrent infection. A recent multicenter study demonstrated safety and efficacy of FMT for the treatment of recurrent or refractory CDI in IBD patients with cure rates comparable to the general population, but questions still remain regarding the impact of FMT on underlying IBD and its position in the treatment paradigm.

Yao-Wen Cheng1 Monika Fischer2 1Resident, Department of Medicine, Indiana University School of Medicine 2Assistant Professor, Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN

INTRODUCTION

Clostridium difficile infection (CDI) is the most prevalent cause of nosocomial infectious diarrhea in developed countries.1 Over the past decade its incidence has doubled,2,3 a phenomenon attributed to the emergence of an epidemic strain of C. difficile known as North American pulsed-field type 1, PCR ribotype 027 (NAP1/BI/027),4 an accelerated toxin producer associated with greater disease severity, higher relapse rates, and significant mortality.5 Its financial burden on the healthcare system is estimated to be up to $3.2 billion annually in the United States.6 The impact of CDI on patients with inflammatory bowel disease (IBD) is even more pronounced. Over the past decade, the incidence of CDI has doubled in Crohn’s disease (CD) and tripled in ulcerative colitis (UC).7 More importantly, the prevalence of CDI in the IBD population (CDI-IBD) is estimated to be 2.5 to 8-fold higher than the general population, with a 10% lifetime chance of infection.8-10 In 2007, 2.9% of all IBD hospitalizations in the US were complicated by CDI.11 Beyond the alarming rise of CDI incidence disproportionate to the general population, hospital admissions for CDI-IBD result in worse outcomes when compared with CDI alone or IBD alone. In-hospital mortality is four to six times greater for patients admitted for CDI-IBD compared to IBD alone.12,13 Furthermore, patients with CDI-IBD have a twenty-fold increase in colectomy rate compared to patients with IBD alone,11 and six times greater colectomy rate compared to patients with CDI alone.12 Length of hospital stay and costs associated with hospitalization are also significantly higher when CDI- IBD is compared to IBD or CDI-related admissions.12,13

Fecal microbiota transplant (FMT) has emerged as a highly effective therapy for recurrent CDI.14 There is also strong evidence that FMT is safe and rarely associated with adverse events even within immunosuppressed populations.15-17 Treatment guidelines published in 2013 by the American College of Gastroenterology recommend FMT for the third CDI recurrence.18 This is predicated on treatment success rates surpassing 90% for recurrent and refractory CDI after just one FMT delivered via colonoscopy to the ascending colon or cecum.19,20 Fecal microbiota transplant via other routes have also demonstrated efficacy rates of roughly 85% when delivered through nasoduodenal tube21,22 or via enema.23,24 More recent studies suggest a role for FMT in hospitalized patients with severe and severe-complicated CDI; cure rates are as high as 88% after a single FMT25 and over 90% when utilized in a sequential manner.26,27

Despite the disproportionately high incidence and poor outcomes associated with CDI in patients with IBD, only a handful of studies have described outcomes after FMT therapy in this population. Among IBD patients on immunosuppressive therapy (N=36), Kelly and colleagues demonstrated CDI resolution in 86% of patients after a single FMT, with an overall cure of 94%.28 More recently, Khoruts et al. showed patients with IBD were more likely to fail a single FMT and that immunosuppressive therapy did not influence the outcome.29 In their study, a single colonoscopic FMT cleared CDI from 74% of patients with IBD compared to 92% of patients without IBD (P = 0.0018). A multicenter study on the use of FMT specifically in IBD patients with recurrent or refractory CDI, the largest study on this subject to date, had the primary goal of assessing treatment success rates for CDI in this unique population, and to describe secondary outcomes pertaining to safety and effect on IBD disease activity.30

Methods

In this retrospective study, patients from seven medical centers with a history of IBD and recurrent or refractory CDI were treated with FMT delivered via colonoscopy or sigmoidoscopy. Protocols for donor selection and stool processing were performed as outlined by the Fecal Microbiota Transplantation Working group.31 IBD activity and severity was assessed based on the judgement of the treating physician, endoscopic findings, and clinical disease activity scores. Results of these assessments were recorded at 1 month pre-FMT, at the time of FMT, and 3 months post-FMT. Changes in IBD clinical course after FMT were categorized by the treating physician as improved, no change, or worsened.

Outcomes of CDI Treatment

A total of 67 patients were included, 35 with CD, 31 with UC, and 1 with indeterminate colitis among which 64% were being treated with immunosuppressive agents at time of FMT. All patients in this group had a history of recurrent or refractory CDI with an average of four episodes. The majority of patients (94%) were previously treated with vancomycin. The indication for FMT was recurrent CDI in 80% and severe or severe-complicated CDI in 9%. Overall, 79% were treated successfully after one single FMT, while 90% achieved success after a maximum of three FMTs. The only independent predictor for a repeat FMT was low serum albumin concentration.

Impact of FMT on IBD

Seventy-six percent of this CDI-IBD population had endoscopic evidence of active IBD during FMT. After 3 months, the majority of patients were “doing well”; the IBD clinical course had improved in 46.3% and went unchanged in 35.8% of patients. Clinical disease activity score (Harvey-Bradshaw index) was available for 23 CD patients and decreased significantly from a mean of 7 pre-FMT to 2 post-FMT (P = 0.004). However, a significant minority of patients (17.9%) had worsening of their IBD clinical course. Among those patients considered to be worse, three had extensive colitis at the time of FMT and were hospitalized for an IBD flare in the ensuing 2 weeks post-FMT, but responded promptly to a short course (10-30 days) of systemic steroids. Two patients proceeded to colectomy within 1 month, both for severe Crohn’s colitis and therapy-refractory CDI. Two other ulcerative colitis patients underwent proctocolectomy, but were noted to be negative for CDI by PCR at the time of surgery. Nineteen patients were started on a new IBD therapy during the 12 week follow up period.

Overall, 12% (8/67) of patients experienced a serious adverse event (SAE), two of which were IBD flares requiring hospitalization. Only one patient experienced an SAE directly attributable to FMT; this immunocompromised CD patient in clinical and endoscopic remission at the time of FMT, developed a flare 1-week post-FMT and was found to have active inflammation and CMV-positive cells on subsequent colonic biopsies. CMV could have been transmitted through the stool transplant; neither the donor nor recipient was tested for CMV prior to the FMT. Notably, no other infectious complications related to FMT were reported.

How Will FMT Change the Treatment Paradigm For CDI-IBD?

This study demonstrated the efficacy of FMT as an adjunct to medical therapy for the treatment of CDI in the IBD population. It reaffirms success previously documented in case series28,29,32 and derives a cure rate comparable to the general population. The majority of patients had an improved or unchanged IBD course post-FMT, but a significant minority developed an IBD flare or had worsening disease activity. These findings are consistent with a previous study on immunocompromised patients where 14% of patients in the IBD subset experienced an IBD exacerbation after FMT.28 More recently, Khoruts et al. reported that 25% of IBD patients had a flare requiring systemic steroid therapy after FMT.29 Importantly, a majority of these patients had severe colonic inflammation at the time of FMT. Given the considerable portion of patients who experienced an IBD flare post-FMT, the authors adopted the practice of increasing anti- inflammatory/immunosuppressive therapy in patients with severe underlying colitis to mitigate the risk of post-FMT IBD flare. In another study, Chin and colleagues administered FMT to 35 CDI-IBD patients primarily via oral capsules.33 While FMT was well tolerated by all patients, a large portion (54%) required therapy escalation for IBD after FMT. Interestingly, two patients developed de novo disease in the form of perianal fistula and abscess post-FMT. The cause of post-FMT IBD flare and worsening disease activity is unknown. Conceivably, the flares could be precipitated by Clostridium difficile infection itself versus natural IBD progression, and/or an immune reaction triggered by FMT administration. Prospective studies on temporal changes in the gut microbiota composition are needed to gain mechanistic insights.

Patients with IBD have multiple risk factors for CDI including dysbiotic gut flora and higher rates of exposure to immunosuppressive medications, antibiotics, and hospitalization, which collectively lead to conspicuously worse morbidity and mortality outcomes.34,35 Yet, patients with CDI-IBD are treated under the same guidelines as their non-CDI counterparts. There is a role for a more aggressive treatment methodology. Mounting evidence supports the use of vancomycin in CDI-IBD as first line therapy even for non-severe CDI. In one study, patients with UC and non-severe CDI had fewer readmissions and shorter length of stay when treated with vancomycin-containing regimens than those with metronidazole alone.36 Lower rates of colectomy were reported when CDI-IBD patients were treated with oral vancomycin.37 There is a need for CDI disease severity stratification specific to the IBD population. Both elevated white blood cell count (WBC) and serum albumin concentration below 3g/dL are characteristic of severe disease and independently associated with colectomy and death in the general population.38 In the CDI-IBD population, serum albumin below 3g/dL was associated with a three-fold increase in the primary outcomes of colectomy and death, irrespective of the white blood cell count.39

There are improved outcomes in CDI-IBD patients after usage of vancomycin even for non-severe cases. The severity of disease may possibly be masked by the concurrent use of immunosuppressive medications and delayed recognition of CDI due to the similarities in patient symptomatology during an IBD flare and CDI. Further, delay in recognition of CDI severity even after colonoscopy may be due to the lower frequency of pseudomembranous colitis in CDI-IBD patients. Fifty percent of non-IBD patients with CDI have pseudomembranous disease,40 but only 13% of patients with CDI-IBD in a large cohort study had pseudomembranes identified during colonoscopy.41 Pseudomembranes, as a marker of disease severity in non-IBD patients, did not have an association with length of stay or adverse clinical outcomes in this set of CDI-IBD patients.41 These factors may result in suboptimal treatment, which is further exacerbated by declining response rates to metronidazole even in non- severe patients. Initial CDI response to metronidazole was >90% in 1983,42 but have now dropped to roughly 50%.43

There may be a role for earlier positioning of FMT for the treatment of CDI in the IBD population even though current evidence for FMT in the treatment of IBD without concurrent CDI is weak at best.44 Rates of admission for CDI recurrence are much higher for patients with IBD (8.7%) versus the general population (0.1%).7 However, there still appears to be unpredictability in the response to FMT in the IBD population. Our patients also had variable responses in IBD activity after FMT therapy with 17.9% citing worse symptoms. The variable clinical courses of IBD after FMT could well be explained by a “donor effect,” which has been raised after a recent randomized controlled trial using FMT to treat patients with mild to moderate UC, documented a particular donor being particularly effective at inducing remission in these patients.45 Fluctuations in the composition of commensal organisms occur over time,46 combined with the idiosyncratic response to therapy due to the heterogeneity of recipients’ underlying IBD, may explain why only some patients have improved IBD activity after FMT. Prospective, longitudinal studies are required to determine the optimal timing for FMT in the treatment of CDI-IBD, to ensure the best outcomes while curtailing worsening IBD activity post-FMT.

CONCLUSION

Current data suggest that FMT for the treatment of recurrent or refractory CDI is effective and safe in patients with inflammatory bowel disease. The overall cure rate in CDI-IBD patients is comparable to non- IBD patients, however IBD patients may need more than one FMT for cure. While the majority of CDI- IBD patients’ clinical course improves following FMT, some remain unchanged despite CDI clearance and a significant minority may experience an IBD flare. Hospitalizations related to CDI-IBD portend much higher rates of mortality, colectomy, and hospital length of stay compared with CDI or IBD alone, therefore FMT may need to be considered earlier on in this population. To effectively treat these patients and decide where to position FMT in the treatment paradigm, further studies of FMT on CDI and IBD outcomes are needed.

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Nutrition Issues In Gastroenterology, Series #159

Medicare Coverage for Home Parenteral An Oxymoron Nutrition What Does it Take to Qualify For HPN

January 2017 • Volume XLI, Issue 1
Penny Allen

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In this second part of a two part series on Medicare policy for HPN, we examine real life Medicare HPN referrals, discuss how to assess if a patient/beneficiary qualifies for coverage, and provide suggestions for alternative options when no coverage for home infusion therapy is provided.

Penny Allen, RD, CSNC National Director, Nutrition Support Lead for Medicare Clearance, Parenteral Nutrition, AxelaCare Health Solutions

Physicians and healthcare providers charged with caring for patients requiring home parenteral nutrition (HPN) face increasing pressure to discharge patients earlier from the acute setting. Patients with gastrointestinal (GI) disorders or GI/nutritional complications from cancer treatments and other conditions may require continuation of parenteral nutrition (PN) therapy in the home setting. As the population of Medicare eligible beneficiaries grows, it is often a surprise at the time of discharge that many Medicare patients do not have coverage for HPN and the related medically necessary infusion therapies under the current Medicare system. In this second part of a 2 part series on Medicare policy for HPN, we examine real life Medicare HPN referrals, discuss how to assess if a patient/beneficiary qualifies for coverage, and provide suggestions for alternative options when no coverage for home infusion therapy is provided.

INTRODUCTION

A 67 year old female patient with Stage III ovarian cancer presents with a partial small bowel obstruction and intractable nausea and vomiting; she is referred to a home infusion provider for home parenteral nutrition (HPN) on a Friday afternoon. The patient has Medicare as her primary insurance along with a supplemental policy. The physician and case manager are told:

“I am sorry, your patient does not have coverage for HPN under Medicare.”

In last month’s edition, the current (and very outdated) Medicare parenteral nutrition (PN) policy was reviewed, along with a call to action to support the Medicare Infusion Site of Care Act which would provide more meaningful infusion benefits for Medicare beneficiaries.1 In this article, real life referral case studies will be reviewed. Guidance for the clinician trying to obtain the appropriate supporting documentation to meet coverage criteria for a beneficiary requiring HPN will be provided (see Table 1 for clinical conditions that are unlikely or will not be covered by Medicare). For a review of policy details, see last month’s issue with reference tables and checklist.

Referral 1

Partial small bowel obstruction due to ovarian cancer

  • 1. Possible “Situation” in Medicare policy that HPN would be covered? (All “Situations” referred to in the following referral scenarios are quoted verbatim from Medicare policy).
    Situation D1,2
    “The beneficiary has complete mechanical small bowel obstruction where surgery is not an option”
  • 2. Assessment
    Since the beneficiary only has a “partial” obstruction, she does not meet Situation D exactly so Medicare deems this a “moderate abnormality”.2
  • 3. Required for coverage for a “moderate abnormality”:

    a. Situation G and H criteria (See Part I of this series for detail).1,2

    b. Estimated length of need for HPN documented in the medical record by the attending physician, must be at least 3 months.2

    c. A thoroughly documented tube feeding trial. (See Part I of this series for detail).1,2

Referral 2

Patient diagnosed with short bowel syndrome (SBS), requiring PN and supplemental hydration after a mesenteric infarct and small bowel resection leaving 3 feet (90 cm) of small intestine. Surgery was 3 weeks ago. Patient has Medicare with a supplemental plan that will only cover the 20% patient copay if Medicare pays for the therapy.

  • 1. Possible “Situation” in the Medicare policy where HPN is covered?
  • Situation A1,2
    “The beneficiary has undergone recent (within the past 3 months) massive small bowel resection leaving less than or equal to five feet of small bowel beyond the ligament of Treitz”
  • 2. Assessment
    Patient may meet criteria for Situation A if objective documentation in the medical record supports the initial information provided at time of referral.
  • 3. Required documentation in medical record for Medicare HPN coverage:
    a. Need surgical reports clearly stating there is < 5 feet (150 cm) of small bowel remaining beyond the ligament of Treitz.2 and

    b. Length of need for HPN must be documented in the medical record and must be greater than 90 days.2

Referral 3

Patient referred for HPN with diagnosis of weight loss, intractable nausea and vomiting due to chemotherapy and treatments for pancreatic cancer.

  • 1. Possible “Situation(s)” in the Medicare policy where HPN is covered?

    Unless there is a diagnosis of complete obstruction of the small intestine (Situation D), malabsorption (Situation E), or a motility disorder (Situation F) with the objective documentation required that supports any one of those Situations, it is highly unlikely there is coverage for HPN. Medicare will only cover HPN when there is a permanent impairment to the small intestine. Weight loss, malnutrition, nausea and vomiting are not covered conditions under the current policy; therefore in the majority of cases, cancer and cancer related complications requiring PN are usually not covered in the home setting.
  • 2. Assessment
    a. Review full medical record for any other possible covered Situations (A-F, G and H).1, 2

    b. Check for a major medical secondary insurance policy with PN benefits.

    c. Explore other options such as PN coverage in a skilled nursing facility, patient self- pay capability, or the hospital pays the HPN provider a per diem rate (if the hospital understands the value of getting the patient out of the hospital bed and into a less costly site of care).

    d. Check Part D benefits for partial coverage of PN formula understanding that the patient will have a daily copay for pump and supplies.

Referral 4

Patient is s/p gastric bypass procedure over 5 years ago with subsequent multiple abdominal surgeries and complications. Patient has been unable to tolerate oral intake and has lost over 200 lbs., and now weighs 105 lbs. She presents with significant malnutrition including multiple nutritional deficiencies. PN has been initiated, and case management would like her discharged as soon as possible. Due to longstanding disabilities, she has a Medicare replacement plan that follows Medicare PN policy; it also has exclusion criteria for weight loss surgery and complications.

  • 1. Possible “Situation(s)” in the medical policy where HPN is covered?

    Unless there is a diagnosis of SBS (Situation A or B); bowel rest for pancreatitis, enterocutaneous fistula or severe Crohn’s flare (Situation C); a complete obstruction of the small intestine (Situation D), malabsorption (Situation E), or motility disorder (Situation F) along with objective documentation required to support any one of these Situations, it is highly unlikely there is coverage for HPN. Medicare will only cover HPN when there is a permanent impairment to the small intestine. Weight loss and malnutrition are not covered conditions under the current Medicare policy and this patient’s insurance plan (which follows the Medicare PN policy) also excludes coverage for complications due to weight loss surgeries.
  • 2. Assessment
    a. Review medical record thoroughly for any conditions that may be deemed a “moderate abnormality” if the exact criteria for Situations A-F are not met.

    b. Consider an enteral feeding trial if possible (see Part I of this series).1

    c. Check if patient has a major medical secondary policy with HPN benefits.

    d. Explore other options such as PN coverage in a skilled nursing facility, patient self- pay capability, or the hospital pays a HPN provider a per diem rate

    Care providers should shop for best competitive rate among HPN providers as applicable.

    e. Check Part D benefits for partial coverage of PN formula (understanding that the patient will have a daily copay for pump and supplies).

    f. Check to see if an outpatient infusion center would consider providing PN for a specific number of days/week. Not ideal or convenient for the patient due to the length of time to administer PN. Medicare replacement plans can vary greatly in regards to coverage.
  • 3. Requirements for coverage if there is a “moderate abnormality” as defined by Medicare:
    See Part I of this series.1, 2
    “Beneficiaries who do not meet criteria A-F must meet criteria 1-2 (modification of diet and pharmacologic intervention) PLUS criteria G and H below:
    • G. The beneficiary is malnourished (10% weight loss over 3 months or less and serum albumin less than or equal to 3.4 gm/dl), and
    • H. A disease and clinical condition has been documented as being present and it has not responded to altering the manner of delivery of appropriate nutrients (e.g., slow infusion of nutrients through a tube with the tip located in the stomach or jejunum).”

Referral 5

Patient with chronic pancreatitis and malabsorption referred for HPN. The case manager wants a discharge today and the patient has Medicare and a Blue Cross secondary insurance plan.

  • 1. Possible “Situation(s)” in the Medicare policy where HPN is covered?
    Situation C
    Includes three scenarios under “bowel rest” category, one of which is symptomatic pancreatitis with or without pseudocyst:
    “The beneficiary requires bowel rest for at least 3 months and is receiving intravenously 20-35 cal/kg/day for treatment of symptomatic pancreatitis with/without pancreatic pseudocyst, severe exacerbation of regional enteritis, or a proximal enterocutaneous fistula where tube feeding distal to the fistula isn’t possible”.1,2
  • 2. Assessment
    Patient has the possibility for coverage under Medicare for HPN. Conduct a thorough medical chart review to assess if the documentation exists to support criteria for “symptomatic pancreatitis with or without pseudocyst,” i.e., cannot only have a history of pancreatitis, the pancreatitis must be the active problem causing the patient to require PN, and it must be documented that bowel rest is indicated. The words “bowel rest” must be in the medical record, even if NPO (nil per os) status is documented. If documentation does not exist, therapy is expected to be < 3 months, or the patient is not on bowel rest; the secondary Blue Cross (BC) insurance should be investigated concurrently to ascertain if there is coverage under the BC policy if HPN is not covered under Medicare. If the patient is eligible for HPN benefits, and the patient does not meet Medicare criteria, then Medicare would still need to be billed for a specific type of denial code in order to bill the Blue Cross plan.
  • 3. Required documentation in medical record for Medicare HPN coverage:

    a. Statement in medical record by attending physician that bowel rest is required for greater than 3 months.2

    b. PN prescription provides 20-35 cal/ kg of actual body weight/day, or there is documentation from the attending physician in the record explaining why calories fall outside of the range.2

    c. Diagnosis must be symptomatic pancreatitis (not a history of pancreatitis).2

Referral 6

Patient with longstanding SBS for years, previously on HPN and weaned off. After 6 months with no PN, the patient is admitted to the hospital in acute renal failure with weight loss, electrolyte abnormalities and a high output ileostomy. The patient turned 65 years old during the time off PN and now has Medicare with a supplemental insurance policy. The medical team has started the patient on PN in the hospital, corrected the fluid and electrolyte abnormalities and brought renal status back to baseline. They would like the patient to go home on PN and supplemental hydration.

  • 1. Possible “Situation(s)” in the Medicare policy where HPN is covered?
    Situation A1,2
    “The beneficiary has undergone recent (within the past 3 months) massive small bowel resection leaving less than or equal to 5 feet of small bowel beyond the ligament of Treitz, or”
    Situation B1,2
    “The beneficiary has a short bowel syndrome that is severe enough that the beneficiary has net gastrointestinal fluid and electrolyte malabsorption such that on an oral intake of 2.5-3 liters/day the enteral losses exceed 50% of the oral/ enteral intake and the urine output is less than 1 liter/day”
  • 2. Assessment
    If a patient has been off PN for greater than 60 days, Medicare deems this a “break in service” and the patient must be requalified all over again. This patient does have SBS, but if the records reveal there have been no new bowel resections in the last 90 days, then Situation A is not an option–the surgery which left the patient with < 5 feet (150cm) of small intestine was over 3 months ago. The entire medical record should be reviewed to assess if the objective information is available to meet Situation B.

    Medicare does not cover hydration therapy; therefore supplemental hydration would not be covered.3
  • 3. Required documentation in medical record for Medicare HPN coverage:
    a. Diagnosis of short bowel syndrome.

    b. Statement of length of need for HPN by the attending physician (must be > 3 months).

    c. Lab records: abnormal electrolytes upon admission to the hospital.

    d. An intake and output (I & O) flow chart documenting:
    • Oral/enteral intake of 2.5-3.0 liters/day
    • > 50% of the above intake as output/ enteral losses (i.e., > 1250-1500 mL/day), and
    • Urine output must be < 1 liter (It is advantageous to minimize IV fluid intake during the 24 hour time period the I & O is documented, so as not to increase urine output over what it would be at home).
  • 4. Challenges with Situation B:
    a. Electronic medical record I & O charts often do not demonstrate clear delineation of IV intake vs. oral/enteral intake. If not clearly documented all I & O should be done manually so the results are accurate and easy to interpret in preparation for future audits with CMS.

    b. If the patient was given multiple liters of intravenous fluids at the time of admission, urine output may initially be greater than 1 liter, which would not meet Medicare’s criteria. Once the patient is stabilized, a detailed I & O should be repeated to allow for a more true assessment of a lower urine output in the setting of short bowel syndrome if the patient were on an oral/ enteral diet only.

    c. Many patients who are ill cannot consume 2.5-3 liters orally or enterally, however, under Medicare policy, there is no exception to this, so if the patient cannot consume (or infuse enterally) at least 2500 mL, then there would be no coverage under Situation B.
  • 5. Options for provision of supplemental hydration:
    a. Self-pay pricing for supplemental hydration (healthcare providers and patients should shop around for best pricing if possible).

    b. Determine if a higher volume PN solution is possible and would meet the patient’s needs. Stability of a more dilute PN solution may be an issue, but there are options to address this.

    c. Patient goes to an outpatient infusion center (usually Monday-Friday operations) where Medicare would pay for the infusion.

    d. Check for additional major medical policies where hydration (and PN) is usually a covered benefit.

    e. During open enrollment periods (October- December), the patient has the option to select another type of Medicare plan which covers home infusion, understanding they may need home infusion for the long term and benefits under straight Medicare are limited. Medicare.gov lists options per zip code for the individual beneficiary.

Referral 7

69 year old female with SBS with < 6 feet of small bowel (exact amount not quantified in the medical record) and one-third of the distal colon remaining. She has been able to maintain the low end of ideal body weight range, but has had multiple admissions for dehydration. Patient cannot maintain urine output > 800mL/day; when more fluid is consumed, stool output increases. Creatinine levels have been slowly rising with levels ranging between 1.3 to 1.5mg/dl. When the patient gets admitted for dehydration and receives IV fluids, the creatinine drops to 1.1-1.2. The patient requires IV hydration at home to protect renal function and the physicians are asking why this is not possible.

  • 1. Possible “Situation(s)” where HPN or intravenous hydration may be covered?

    Unfortunately, Medicare simply does not cover hydration in the home.3

    Options for the patient would be self-pay or when allowed to change Medicare plans (October -December is open enrollment), investigate alternative Medicare Advantage plans in the patient’s geographic area that cover home infusion therapy (including hydration and/or PN). Although inconvenient, hydration therapy is covered by Medicare in an outpatient infusion clinic (see above options for provision of supplemental hydration under Referral 6).
  • 2. Assessment
    Since the patient does have SBS, Situations A or B may be potential options. Situation A would require an operative report clearly stating how much small bowel is remaining. If a resection resulted in < 5 feet of small intestine beyond the ligament of Treitz, and the resection was in the last 3 months-then there would be coverage.

    If not, we are left with Situation B. If the patient is subsequently admitted again for dehydration, the above guidance and recommendations listed in Referral 6 for Situation B should be followed. This should occur in the institutional setting to ensure clear documentation in the medical record (i.e., the legal document).

    With Situations A, B and D in the Medicare PN policy, the calorie range provision (i.e., PN must provide 20-35 calories/kg of actual body weight) is not required, so if the physician documents clearly what the patient needs are due to her SBS, a more dilute PN prescription may be covered which could meet her fluid and electrolyte needs.

    “NUTRIENTS:
    Parenteral nutrition solutions containing little or no amino acids and/or carbohydrates would be covered only in situations A, B or D discussed in the Parenteral Nutrition – Policy Article A total caloric daily intake (parenteral, enteral and oral) of 20-35 cal/kg/day is considered sufficient to achieve or maintain appropriate body weight. The ordering physician must document in the medical record the medical necessity for a caloric intake outside this range in an individual beneficiary. This information must be available on request”.2

Referral 8

68 year old obese female with enterocutaneous fistula and wound vac referred for home PN. PN prescription provides 17 calories/kg actual body weight/day. Patient has Medicare for primary insurance and an American Association of Retired Persons (AARP) Medicare supplement policy.

  • 1. Possible “Situation(s)” in the medical policy where HPN is covered?
    Situation C1,2
    “The beneficiary requires bowel rest for at least 3 months and is receiving intravenously 20 -35 cal/kg/day for treatment of symptomatic pancreatitis with/without pancreatic pseudocyst, severe exacerbation of regional enteritis, or a proximal enterocutaneous fistula where tube feeding distal to the fistula is not possible”
  • 2. Assessment
    This patient has a chance at Medicare coverage under Situation C depending on a number of variables.

    Required documentation in the medical record for Medicare HPN coverage:

    a. Diagnosis of enterocutaneous fistula in the medical record.2

    b. Statement by attending physician that bowel rest is required for at least 3 months. Medicare specifically defers to the language of “bowel rest” not “NPO”.2

    c. PN prescription must provide 20-35 cal/kg of actual body weight/day. If not, documentation from the attending physician explaining why calories fall outside of the range must be in the medical record.2

    d. Statement that tube feeding distal to the fistula is not possible (a fistulagram or other objective study is helpful, but not mandated by the policy).2

CONCLUSION

Until new laws are passed and coverage for home infusion/PN becomes more meaningful under Medicare, healthcare providers must carefully assess the need for HPN therapy. Referrals for homecare should be made as early as possible to allow for thorough examination and review of medical documentation and allow for the possibility that Medicare may require additional testing. This will help ensure that the beneficiary will have coverage for HPN and is not at risk for denial of payment should an audit determine that coverage criteria was not met, potentially leaving the patient and family with a significant bill in the future.

All healthcare providers involved in the care of patients requiring HPN and related therapies should develop a stronger understanding of the Medicare reimbursement system in order to advocate for the needs of this challenging patient population. Failing to do this may prevent patients from having access to life sustaining nutrition support and could also expose them to significant financial harm. Given these risks, clinicians would be well advised to carefully document the clinical necessity of HPN, backed up by objective evidence and testing, along with an estimated length of need for the therapy for all patients going home on PN- -as if they needed to meet Medicare criteria. Patients who currently have private insurance may eventually transition to Medicare and supporting documentation will be required for a successful transition and continuation of HPN therapy. More information regarding the Medicare Home Infusion Site of Care Act can be found at nhia.org.

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Frontiers In Endoscopy, Series #33

Endoscopic Bariatric Interventions in the Management of Obesity: The Era of Non-Surgical Management

January 2017 • Volume XLI, Issue 1
Truptesh H. Kothari,Paridhi Malik,Shivangi Kothari,Vivek Kaul

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In this article we discuss bariatric endoscopy, a newly developing field in the management of obesity by inducing weight loss associated with a minimal complication profile. Although some therapies currently remain under FDA evaluation and trials, the emergence of endoscopic bariatric therapies holds a promising future.

Truptesh H. Kothari MD, MS Paridhi Malik MD Shivangi Kothari MD Vivek Kaul MD Division of Gastroenterology – Hepatology, University of Rochester Medical Center, Rochester NY

Obesity is defined as a complex metabolic disease of fat accumulation associated with increased risk to health. Body Mass Index (BMI) is a measure to classify obesity in adults. It is a calculated by dividing a person’s weight in kilograms by the square of his height in meters (Kg/m2). According to the World Health Organization, obesity is defined as individuals with a BMI ≥ 30. Further categorization of obesity is done based on the severity of BMI over 30. Class I refers to BMI of 30-34.9, Class II refers to BMI 35-39.9, and Class III refers to BMI over 40.1 Recent statistics from a National Health and Nutrition Examination Survey (NHANES) in 2013-2014 reveal that 32.7% of adults in the U.S above the age of 20 are overweight (BMI 25-30), 37.9% are obese, and 7.7% are severely obese with BMI of more than 40.2 The reported average BMI in the year 2000 was 30 whereas it is 33.6 in 2016.

The behavioral risk factor surveillance system is an ongoing nation-wide telephone-based survey, which is conducted by the CDC. The most recent results of this study in 2015 reveals a total of 19 states with obesity rates between 25% and 30% along with four states (Alabama, Louisiana Mississippi, and West Virginia) with a prevalence of Obesity upwards of 35% of the population.3 Obesity carries a major risk to an individual’s health with 55% increase in mortality, 70% increase in coronary artery disease, 75% increase in stroke risk and a 400% increase in diabetes risk. Obesity and being overweight accounts for about 2.8 million preventable deaths annually and certainly has become a global epidemic.4

Current management of obesity includes a range of interventions from lifestyle modifications and medical therapy to invasive surgical procedures (Figure 1). Weight loss is the major lifestyle modification used in controlling obesity; however, it has proven to show only moderate improvement in obesity. “An alternative approach to managing obesity is pharmacotherapy, which is considered useful as an adjunct to lifestyle modifications. This approach results in weight loss by an additional 3 to 9% in comparison to the lifestyle modification alone”.5 Although anti-obesity medications assist in achieving good weight loss results, they carry a high risk of relapse and weight gain. Bariatric surgery is considered in individuals who fail to improve with lifestyle modifications and/or medications. It is also recommended for those with BMI > 40 Kg/m2 or, BMI of 35 Kg/m2 or more with comorbid conditions such as hypertension and type 2 diabetes. Some of the most commonly performed surgical weight loss procedures are Roux-en-Y gastric bypass, sleeve gastrectomy, and gastric banding. Several endoscopic (non-surgical) options have emerged for obesity management in the last decade.

Although Bariatric surgery remains an efficient and durable option for obesity management, less than 1% patients undergo bariatric surgery. The low usage of the surgery may be attributed to surgical cost, patient preference, access to care, and the mortality- morbidity associated with this procedure. Some of the major complications reported after a surgical bariatric procedure are luminal obstruction, anastomotic leak, marginal ulcer, gastrointestinal bleeding, wound related complications, and pulmonary embolism. The complication rates of bariatric surgical procedures remain high at 17%.6 The high complication rates of surgery led to the need for developing a less invasive alternative that reduces morbidity and can provide quick access to patient care. This gap in the management options has led to the evolution of bariatric endoscopy. Bariatric Endoscopy is a newly developing field in the management of obesity by inducing weight loss associated with a minimal complication profile.

Endoscopic bariatric interventions are classified based on site of intervention and can be either a Gastric or a Small Bowel intervention. Gastric interventions include space-occupying devices such as intragastric balloons, TransPyloric Shuttle, and Full Sense Device along with Aspiration therapy and Gastroplasty techniques. These devices work via different mechanisms to induce early satiety, including increasing the stimulation of mechanical and chemical receptors in the gastric tract, delaying gastric emptying and reducing luminal accommodation thus limiting food intake by inducing early satiety (Table 1).

Small bowel interventions interfere with nutritional absorption by various mechanisms depending on the technique (Table 2). Of note, currently, none of the small bowel endoscopic bariatric interventions discussed are FDA approved or commercially available in the USA.

Clinical evaluation of the Orbera device was performed in a prospective randomized controlled, comparative clinical study using 125 subjects in the treatment group and 130 subjects in the control group with BMI of 30 – 40 Kg/m2. The treatment group underwent Orbera placement followed by removal after six months. Both groups participated in a twelve-month behavioral modification program. The effectiveness of the study was measured with two co-primary endpoints. This included first, the mean percent excess weight loss (EWL) at nine months (3 months after the balloon was removed) and secondly, if >30% of Orbera-treated subjects achieved significantly greater (>15% estimated weight loss) weight loss over the mean %EWL of the control group. The study did not meet its first co-primary endpoints as the mean %EWL did not meet the 95% lower bound confidence interval, although the study did satisfy the second co- primary endpoint with 45.6% Orbera treated patients exceeding 15% mean EWL over the control subjects. Total body weight loss in the Orbera group was noticed to be a mean of 10.2% and 9.1% at 6 and 9 months after balloon insertion respectively. Significant weight loss was observed within the Orbera group as compared to the control group with a mean % excess weight loss with ideal weight defined as BMI of 25. It was found to be 38.4% at month 6, 34.6% at month 9, 29% at month 12 as compared to 12.1%, 12.3% and 11.1% in the control group with a p-value of <0.001. % Total body weight loss of 10.2, 9.1, 7.6 % in the Orbera and 3.3, 3.4, 3.1 % in the control group at 6, 9 and 12 months after the insertion of the balloon with a p-value of <0.001. Secondary effectiveness of the intervention was measured by the impact of treatment on comorbid conditions such as Hypertension, Type 2 Diabetes and dyslipidemia at months 6, 9 and 12. It was noticed that both groups experienced a comparable decrease in the severity of the comorbid conditions, which may be as a result of a common factor in both groups such as diet and exercise. P-values were not statistically significant to prove a difference between the Orbera and control group when comparing the decrease in severity of hypertension, diabetes and dyslipidemia. Orbera pivotal trial revealed that patients could expect to achieve three times the weight loss at six months as compared to diet and exercise alone, majority of which is lost in the first three months (Figure 2.a., 2.b., 2.c.).

A longitudinal and interventional study was performed in obese patients over six months after placement of an intragastric balloon aimed to study the effect of the treatment on lung function, BMI, and DXA parameters. It was noted that lung volumes were significantly reduced at six months after balloon placement. A drop in BMI was also noticed from 39.1 Kg/m2 to 34.5 Kg/m2. Considerable improvement in body fat distribution was also reported using DXA measurements of body fat.7

A randomized clinical study was performed to evaluate the safety and efficacy of the ReShape dual balloon system (DBS) by comparing two groups of patients: one with DBS treatment along with diet and exercise and one that was a control group with diet and exercise only (Figure 3). The study included a total of 326 individuals with 187 in the DBS group and 139 in the control group. The BMI of the targeted patient population was between 30-40 Kg/m7. The study revealed a significant effect in the DBS group as compared to control. The effectiveness was measured using two co-primary endpoints. The first primary endpoint was defined by the percent excess weight loss (%EWL) and the second primary endpoint measured if more than 35% achieved a 25% EWL in the treatment group at 24 weeks when the dual balloon system was retrieved. This pivotal trial successfully met both the co-primary endpoints. It was found that the weight loss was more than double as compared to the control group along with a %EWL of 25.1% in the DBS group (intention-to-treat). This is significantly greater than the control group with a %EWL of 11.3%. The second primary endpoint was also met as there was a 49.1% difference in the treatment group who achieved a 25% EWL, this was considerably over the 35% response rate.8

A prospective study of 150 patients was performed in patients who regained weight post-Roux-en-Y gastric bypass (RYGB) surgery. The targeted patient population included patients with Gastrojejunal anastomosis (stoma) aperture larger than 15mm. This study aimed to recognize the long-term benefits of management of dilated anastomosis aperture post-RYGB using an endoscopic procedure called Transoral Outlet Reduction (TORe). The study focused on trending weight loss at 3, 6, 12, 24, and 36 months after completion of the TORe procedure. It was reported that a weight loss of 9 to 11 kg and a BMI loss of 3 Kg/m2 was achieved as a result. This was as a result of a decrease in aperture size from 24.1 + 1mm to 9.0 + 0.2mm. The adverse effects were limited to abdominal pain in 4% patients, gastrointestinal bleeding in 3.3% and nausea in 2.0%. It was shown that a greater reduction in anastomotic aperture was associated with a greater post-procedural weight reduction.9 TORe, being less invasive, is a safe and reliable alternative in the treatment of post-surgical complications of RYGB.

Obesity is one of the leading health problems in the United Status today and is becoming very challenging to manage. Despite numerous management options varying from lifestyle modifications to bariatric surgery, obesity remains a problem unsolved. It comes with its wide array of comorbidities increasing the financial burden of this widespread epidemic even further. As a result, it has become one of the top priorities in today’s healthcare. Endoscopic techniques allow for the management of obesity in a less-invasive manner and help prevent the associated risks of the bariatric surgical procedures. It also allows for a holistic approach to manage obesity with endoscopic intervention being the primary tool complemented by its behavioral modification program and comprehensive follow-up strategies. Although some of the therapies currently remain under FDA evaluation and trials, the emergence of endoscopic bariatric therapies holds a promising future in the way obesity will be managed. This is indeed a revolutionary step towards medical and surgical management of obesity.

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A CASE REPORT

Primary Malignant Fibrous Histiocytoma of the Cecum

December 2016 • Volume XL, Issue 12
Patrick C Bonasso,Jared Feyko,Nezar Jrebi

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We report the case of a 70 year-old female with a palpable abdominal mass and anemia. After colonoscopy was inconclusive for diagnosis, resection via laparoscopic right hemicolectomy revealed malignant fibrous histiocytoma of the cecum. This case discusses the pathology and treatment of this rare disease.

Patrick C Bonasso, MD; Jared Feyko, DO; Nezar Jrebi, MD Department of Surgery, Ruby Memorial Hospital, West Virginia University; Division of Surgical Oncology, West Virginia School of Medicine

CASE PRESENTATION

A 70-year-old female presented with abdominal pain, fatigue, anorexia and weight loss. On exam, she had a palpable abdominal mass in the right lower quadrant. Her initial laboratory values revealed severe microcytic, hypochromic anemia with a hemoglobin of 7.6 g/dL. Her white blood cell count (WBC) was 5.4 thou/mcL, platelets 350 thou/mcL, creatinine 0.5 mg/ dL and carcinoembryonic antigen (CEA) less than 0.2 ng/mL. Computed tomography (CT) of the abdomen and pelvis showed a mixed density lobular cecal mass measuring 7.5 x 10.2 x 7.9 cm with several enlarged lower right mesenteric lymph nodes (Figure 1).

The patient was admitted and underwent colonoscopy with biopsy (Figure 2). Pathology showed ulceration with inflammation and scattered atypical cells suspicious for malignancy. She was taken to the operating room and underwent laparoscopic right hemicoloectomy (Figure 3). She progressed through hospitalization without any complications. She tolerated a regular diet and was discharged on postoperative day three.

Final pathology revealed a neoplasm composed of large, pleomorphic giant cells and spindle cells, arranged in fascicular and storiform pattern mixed with inflammatory cells infiltration, including lymphocytes, plasma cells, polymorphonuclear leukoocytes (PMNs) and multinucleated giant cells. Immunohistochemical (IHC) staining showed positive reaction of tumor cells with a1 antitrypsin, Vimentin and focal smooth muscle actin (SMA). The tumor was Grade III with 9 out of 21 lymph nodes positive for malignant disease.

Discussion

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in adults.1 Common locations of this sarcoma include the lower and upper extremities (most common, 46%), retroperitoneum, abdominal cavity, head and neck.

Primary MFH in the alimentary tract is rare. There have only been 25 reported cases in the colorectal literature,2 most commonly in the right colon. Often these tumors are large with an average size of 8.1 cm and a range of 2-19 cm. Review of previously reported cases show a male to female ratio of 2.3:1 with an average age of 55.7 years. Most of the tumors were solitary, but some were multiple.

Common presenting symptoms include abdominal pain, fever, palpable mass, bloody stools, diarrhea and anorexia secondary to compression from the large mass. Laboratory values commonly include leukocytosis, elevated erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP). Predisposing factors include genetics, exposure to radiation or chemotherapy, chemical carcinogens, chronic irritation and lymphedema.

Treatment options include radical surgical resection, chemotherapy with cyclophosphamide, vincristine, adriamycin, dimethyl triazenoinidazole carboxamide (CYVADIC) or radiotherapy (5000 to 5400 cGy). The prognosis is unclear with most reports suggesting that outcomes are poor. The overall survival at two and five years is 60% and 47%, respectively.2

The tumor arises from primitive mesenchymal cells that retain histiocytic and fibroblastic potential. Pathology of the sarcoma shows both histiocytic and fibrous elements accompanied by pleomorphic giant cells, xanthoma cells and inflammatory cells. Pleomorphic fibroblastic cells are commonly arranged in a storiform pattern and positive for vimentin and a 1-antichymotrypsin. MFH is further classified into four types: storiform-pleomorphic, inflammatory, myxoid and giant cell. The most common type is storiform- pleomorphic.3

CONCLUSION

We report a rare case of malignant fibrous histiocytoma (undifferentiated pleomorphic sarcoma) of the alimentary tract treated with colon resection.

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FRONTIERS IN ENDOSCOPY, SERIES #32

Introducing POEM in Your Institution: The Blueprint for Launching a New Program in the Endoscopy Suite

December 2016 • Volume XL, Issue 12
Dennis Yang,Peter V. Draganov

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Per-oral endoscopic myotomy (POEM) is a prime example of a hybrid technique derived from NOTES and endoscopic submucosal dissection (ESD). POEM is an endoscopic therapeutic procedure aimed at treating achalasia and spastic esophageal disorders. While POEM was introduced and traditionally performed in the operating room (OR) setting, its well-documented safety and efficacy over the past 8 years has led to its natural acceptance by therapeutic endoscopists worldwide and consequently a growing interest in performing this procedure in the endoscopy suite. This review aims to provide a practical guide of introducing POEM in the endoscopy suite from a gastroenterologist’s perspective.

Dennis Yang, MD Peter V. Draganov, MD Division of Gastroenterology and Hepatology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL

The birth of natural orifice transluminal endoscopic surgery (NOTES) in the early 2000s introduced the revolutionary concept of endoscopy beyond the restrictive walls of the gastrointestinal tract. The initial impetus was subsequently met with skepticism as these novel ideas were crippled by the rudimentary instruments and accessories available on the flexible endoscopic platforms. With advances in technology over recent years, there has been a resurgence of NOTES, as witnessed by the increasing number of interventional endoscopists expanding endoluminal applications outside the confines of the gastrointestinal tract.

Per-oral endoscopic myotomy (POEM) is a prime example of a hybrid technique derived from NOTES and endoscopic submucosal dissection (ESD). Initially introduced as a concept by Pasricha and colleagues in 2007 and translated into clinical application by Inoue et al. in 2008, POEM is an endoscopic therapeutic procedure aimed at treating achalasia and spastic esophageal disorders.1,2 While POEM was introduced and traditionally performed in the operating room (OR) setting, its well-documented safety and efficacy over the past 8 years has led to its natural acceptance by therapeutic endoscopists worldwide and consequently a growing interest in performing this procedure in the endoscopy suite.3 This review aims to provide a practical guide of introducing POEM in the endoscopy suite from a gastroenterologist’s perspective.

There are tangible and intangible benefits of adopting complex procedures such as POEM in the endoscopy unit. Advantages of the endoscopy unit over OR include: (1) better ergonomics for endoscopic procedures, (2) readily available endoscopic equipment and accessories and (3) familiarity of the surrounding environment by the endoscopist and the assisting team. We had previously demonstrated that POEM can be safely and efficiently done in the endoscopy suite based on the experience of our first 52 consecutive patients.4 Since then we have performed an additional 100 cases with excellent clinical response rates to further corroborate our initial results. The POEM program at our institution has become a crucial arm within the spectrum of a comprehensive motility program. That being said, starting a POEM program can be a challenging endeavor and careful planning is essential in order to ensure long-term success and stability. There are several key components that must be addressed prior to launching a POEM program in the endoscopy unit: (1) institutional support, (2) training, and (3) establishing a multi-disciplinary team.5,6

Institutional Support

Institutional endorsement on various fronts should be obtained prior to starting a POEM program. The potential advantage of a POEM program should be discussed, with an emphasis on its role in the establishment of a comprehensive motility program at your institution. While the approach may differ at every institution, one should actively seek and contact all stakeholders, which may include the department chair and division chief, the director of the endoscopy unit and other institutional administrators.

Institutional support in terms of protected time to train in an animal laboratory is highly desirable. In our institution, POEM trainees have full access to a well- equipped animal laboratory which facilitates hands- on experience prior to any attempts in humans. This approach permits a realistic exposure to the procedure while removing the high stakes of a clinical setting. Indeed, the international POEM survey on practice patterns demonstrated that most POEM practitioners underwent preclinical training in animal models before human cases.7

Institutional support must also be obtained to make infrastructural adjustments in the endoscopy unit to facilitate the introduction of POEM. As noted earlier, POEM has been traditionally performed in the OR, an environment conventionally perceived as more adept at managing complex procedures. For POEM to be safely performed, the endoscopy unit should possess amenities on par to what is available in the typical OR. Needless to say, full institutional support to obtain all necessary equipment and accessories is imperative. In our endoscopy suite, we store all POEM-related equipment and devices in a dedicated “POEM cart” (Figure 1). On this cart we do maintain inventory of the dedicated POEM devices such as the TT and the Hybrid knifes (Figure 2 and 3) but also devices for hemostasis, perforation closure, chest tube placement kits and peritoneal decompression needles. This approach expedites the movement of items in and out of the endoscopy room, permits quick and easy access to devices intra-procedurally, and also facilitates inventory control. Furthermore, it is our opinion that the endoscopy unit should have permanently stationed general anesthesia equipment as the POEM procedure requires general endotracheal anesthesia. This approach may be conducive for efficient anesthesia preoperative planning and set-up with reduced room turnover time.

Support from institutional administrators must also be sought on issues related to credentialing, scheduling, billing and coding, which again, may differ widely among centers. Prior to starting POEM, it is important to discuss the goals of such a program with the credentialing/privileges committee. In the absence of standardized training guidelines, there should be a conjoint effort between POEM operators and the institution’s committee to establish the necessary benchmarks that must be met prior to becoming credentialed for this novel procedure. In addition, we believe that a dedicated preprinted POEM procedure inform consent form should be utilized which describes in detail the procedure and potential complications both of which significantly defer from other endoscopic procedures. With regards to scheduling, based on multiple reports and our own experience, POEM cases can generally be completed within 60-90 minutes. Nonetheless, additional time allotment for set up and room turnover must be factored in order to avoid conflict with the scheduling of other cases in the endoscopy unit. In addition to scheduling, issues related to billing and coding should also be anticipated given the novelty of this endoscopic procedure. There is currently no procedural terminology (CPT) code for POEM. However, many centers apply an unlisted esophageal surgical code (CPT code 43499) billed at the relative value units equivalent of that of a Heller myotomy.5,7 Discussion with stakeholders with regards to billing and coding should be undertaken prior to scheduling procedures in order to avoid subsequent denials from payers and ensure proper reimbursement.

Training

POEM is a technically complex hybrid procedure that demands advanced endoscopic skills, knowledge of both gastrointestinal (GI) intra and extra luminal anatomy, and a grasp on how to manage complications, including hemorrhage, tension pneumothoraxes, pneumomediastinum, and esophageal perforations. Developing a curriculum and defining a learning curve are complicated by background differences among operators and the relative low incidence of achalasia. Not surprisingly, there is a wide discrepancy in the learning curve plateau reported in the literature, ranging anywhere from 8 to 20 cases.8-10 Since the principles of POEM are in line with ESD techniques, it appears reasonable that training should follow a similar approach to one previously described for ESD.11 An in- depth understanding of the POEM principles, technical aspects and equipment will be a good starting point. A detailed discussion of this subject is beyond the scope of this manuscript, but multiple resources are available in the published literature. Two recent excellent reviews by the POEM pioneer Dr. Inoue highlight his experience and evolving technical concepts.12,13

In summary, initial exposure can be achieved by attending training courses and observing POEM performed by an expert operator. The trainee should be familiar with all the necessary equipment for POEM and also that required for the management of potential adverse events (i.e. hemostasis equipment, suturing devices, enteral stents). Hands-on training should start with explanted models which may be more cost- effective and allow assessment of the gross specimen following the procedure. Once trainees are comfortable with POEM on the explanted model, progressing to a live animal represents the next natural step. The porcine model is ideal given its long esophagus and anatomical resemblance to that of a human. Following preclinical hands-on training, we strongly recommend that trainees be proctored by an experienced operator, who can provide step-by-step supervision and guidance through the initial cases. There are currently no standardized credentialing requisites for POEM and these are urgently needed as we continue to see the increasing adoption of this technique by interventional endoscopists worldwide.

The POEM Multidisciplinary Team

Establishing a multidisciplinary team is perhaps the most important element when initiating a POEM program. Before the introduction of POEM, a multidisciplinary team approach should be adopted to address various technical and clinical aspects of patient management from pre-procedure evaluation to post-procedural discharge:

  • 1. Motility gastroenterologists play an invaluable role in the nonoperative evaluation of patients and should be involved in the multidisciplinary discussions of potential POEM candidates. Their investment in the POEM program not only aids with the identification and recruitment of patients, but it also facilitates longitudinal patient care and assessment of clinical outcomes post-POEM.
  • 2. Participation of the surgical team is also an indispensable component when initiating the POEM program. The surgical team members should become familiar with the endoscopic aspects of the procedure. In turn, the POEM operator can benefit from the surgeons’ perspective and knowledge of extraluminal anatomy. Surgical team members should be readily available to assist in case of a complex procedure or in the management of adverse events. A contingency plan should be well-outlined prior to initiating cases. Prearrangement of surgical back-up before POEM cases may need to be determined based on their accessibility at each respective institution.
  • 3. Before a POEM program is initiated in the endoscopy unit, it is highly advisable to establish a well-defined anesthesia plan for these patients. Overall, the predetermined anesthesia protocol should include details regarding patient position, type of anesthesia, degree of paralysis, ventilation mode as well as clinical and technical parameters that should be monitored throughout the procedure (i.e. peak airway pressure, tidal volumes, end-tidal carbon dioxide, train-of-4 twitches, oxygen saturation). A standardized anesthesia protocol and clear communication among team members is key; particularly in those endoscopy units where coverage is performed by various different rotating anesthesia providers. Specifics regarding anesthesia management are further detailed in our experience with starting a POEM program in the endoscopy suite.4
  • 4. The POEM nurses and technicians should be an integral part of the team. We strongly recommend that the POEM team practice together with explanted or live animal models in order to become familiar with the equipment, steps of the procedure, and management of adverse events. This approach will permit hands-on training and allow the POEM team identify and fine-tune areas for improvement. More importantly, it is an ideal scenario that will foster cohesiveness among team members prior to embarking on human cases. 5. Surveillance imaging post-POEM procedure is routinely performed in all patients to assess for adverse events (i.e. esophageal mucosal injury, leak, perforation). At our institution, we developed a novel computed tomography (CT) esophagram protocol in conjunction with our radiology department. In a prospective study of 84 patients, we demonstrated that numerous and dramatic post-procedural radiographic findings are captured with the CT esophagram; although most of these do not require any intervention.14 Therefore, radiologists should be educated on the POEM procedure and the spectrum of post-procedure radiographic findings that can be encountered. Their awareness of these imaging findings will facilitate its clinical interpretation and prompt intervention when indicated. Imaging surveillance should be tailored according to local resources, expertise, and feasibility.

In summary, POEM has evolved into a recognized minimally invasive endoscopic approach for the management of achalasia and certain esophageal spastic disorders. POEM can be safely performed by experienced interventional endoscopists in a well-equipped endoscopic suite. Nonetheless, starting a POEM program can be a challenging task. Institutional support, proper training, and developing a multidisciplinary team are the essential building blocks to ensure the successful initiation and establishment of a POEM program.

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NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #158

Medicare Coverage for Home Parenteral Nutrition – An Oxymoron? Part I

December 2016 • Volume XL, Issue 12
Penny Allen

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Physicians and healthcare providers charged with caring for patients requiring home parenteral nutrition (HPN) face increasing pressure to discharge patients earlier from the acute care setting. This article provides the clinician with a review of the very dated Medicare policy for HPN, the criteria and objective documentation still required by law today, as well as strategies for attempting to provide home infusion therapy when Medicare will not cover patients who appropriately need HPN.

A 67 year old female patient with Stage III ovarian cancer presenting with partial small bowel obstruction, intractable nausea and vomiting is referred to a home infusion provider for home parenteral nutrition on a Friday afternoon. The patient has Medicare as her primary insurance as well as a supplemental policy. The physician and case manager are informed: “I am sorry, your patient does not meet the Medicare criteria for home parenteral nutrition.”

INTRODUCTION

Physicians and healthcare providers charged with caring for patients requiring home parenteral nutrition (HPN) face increasing pressure to discharge patients earlier from the acute care setting. Patients with gastrointestinal (GI) disorders, GI and nutritional complications from cancer, and other conditions may require continuation of parenteral nutrition (PN) therapy in the home setting. As the population of Medicare eligible beneficiaries grows, it is often a surprise at the time of discharge that many patients do not meet criteria for HPN and related medically necessary infusion therapies under Medicare. In a recent abstract by a home infusion provider, 42% of medical records reviewed for Medicare PN coverage over a 7 month period did not include objective testing required for reimbursement coverage, even though the diagnoses with potential for meeting criteria were present in the records.1

This article provides the clinician with a review of the very dated Medicare policy for HPN, the criteria and objective documentation still required by law today, as well as strategies for attempting to provide home infusion therapy when Medicare will not cover patients who appropriately need HPN. Regardless of insurance plan, if there is any possibility that a patient may require HPN post discharge, the planning process should begin immediately so that all members of the healthcare team as well as the patient are aware of what is required to attempt to secure coverage.

• What is needed to try to successfully qualify this patient for HPN under Medicare?

• If the patient has no coverage under Medicare, what options exist for patients to receive PN and other infusion therapies which are medically necessary?

BACKGROUND
Medicare HPN Policy Remains the Same Over 20 Years Later

Medicare is the federal healthcare program enacted by Congress as part of Title 18 of the Social Security Act of 1965. It is the largest health insurance program in the United States. Medicare coverage is divided into Parts A, B, C, and D, each of which provides different benefits.

For over 20 years, parenteral and enteral nutrition (PEN) therapies fall under the prosthetic device benefit under Medicare Part B. The analogy utilized by the Center for Medicare and Medicaid Services (CMS) is that parenteral nutrition (PN) and enteral tube feeding (or actually the devices to administer them), replace an organ or function of an organ that is permanently impaired. If specific criteria related to any one of 7 GI conditions “permanently” (defined as ≥ 3 months) prevents the patient from absorbing nutrients needed to maintain weight and strength commensurate with health status, and it is documented objectively in the manner required, then Medicare may cover HPN accessories and/or supplies. In addition to the necessary supplies, the oversight of HPN is ideally performed by an inter- disciplinary team on a weekly basis. This oversight of professional services, clinical assessment, monitoring, or the actual ongoing management of the patient has never been covered under Medicare.

The HPN Policy Under Medicare

Currently, the Parenteral Nutrition Policy A52515,2,3 (which has not changed in over 20 years) states:

“Parenteral Nutrition is covered under the Prosthetic Device benefit (Social Security Act 1861(s)8)

Parenteral nutrition is covered for a beneficiary with permanent, severe pathology of the alimentary tract which does not allow absorption of sufficient nutrients to maintain weight and strength commensurate with the beneficiary’s general condition.”

The Medicare concept of permanent impairment of the small intestine is often a challenging one for many clinicians who approach HPN with the hope that it will be temporary and that patients may over time reduce their PN-dependence through bowel adaptation as well as diet and medication management. The policy goes on to read:

“Prosthetic Benefit Requirements

The beneficiary must have a permanent impairment. Permanence does not require a determination that there is no possibility that the beneficiary’s condition may improve sometime in the future. If the judgment of the attending physician, substantiated in the medical record, is that the condition is of long and indefinite duration (ordinarily at least 3 months), the test of permanence is considered met. Parenteral nutrition will be denied as non-covered in situations involving temporary impairments.

The beneficiary must have:
(a.) a condition involving the small intestine and/or its exocrine glands which significantly impairs the absorption of nutrients or,

(b.) disease of the stomach and/or intestine which is a motility disorder and impairs the ability of nutrients to be transported through the GI system. There must be objective evidence supporting the clinical diagnosis.”

Table 1 provides a checklist outlining the clinical situations (A-H) where Medicare will cover HPN. In addition to meeting the test of permanence (Medicare defines permanence as >90 days), there must be clear objective evidence that the GI tract, specifically the small intestine, is non-functioning. A completed Durable Medical Equipment Medicare Administrative Contractor or DME MAC Information Form (DIF), formerly referred to as a Certificate of Medical Necessity (CMN), a Detailed Written Order (DWO), along with extensive objective documentation from the medical record to support the criteria is the minimum required by the Center for Medicare and Medicaid Services (CMS). The original version of Table 2, published and distributed by the former DMERC (now called DME MAC) Region D over a decade ago, outlines the necessary documentation required for each criteria.

Medicare requires an attempt at tube feeding when there is a “moderate abnormality” (see Table 3) of a condition in Situations A-F (Table 1) and the documentation does not exactly meet criteria for coverage. In this instance, additional information such as documented weight loss, a low albumin, attempts at medication and diet modifications and a tube feeding trial is required. There is currently no exception in the policy allowing for situations where a tube feeding trial may not be clinically appropriate or possible. Criteria outlining the documentation necessary for a failed tube feeding trial is outlined in Table 4.

What Has Changed? The Claims Process and Many, Many Audits

The initial claims submission process is different today than in years past causing confusion among some providers, which could potentially place patients/ families at significant financial risk. Qualifying documentation is no longer submitted with the initial claim; in the past, coverage was approved or denied by CMS from the start. Supporting medical records should be obtained by the infusion/PN provider prior to the start of care so they are available for submission when claims are audited, which is a routine occurrence. The initial analysis of whether a patient has coverage falls completely on the infusion provider. If the provider does not fully understand or interpret the policy correctly, physicians and patients may be provided with an incorrect “approval” by the provider/vendor at time of discharge. To make matters more confusing, CMS will pay claims even when a patient does not actually meet criteria–until the provider is audited and then required to submit the initial supporting documentation. This is often months or even years later. CMS can audit a claim up to three years after a claim has been paid, which could potentially end up being as many as five years after an incident of care or shipment was provided.4 If documents cannot be produced in an audit, the government recoups all payments and the beneficiary could be at risk for the total amount, which could be tens of thousands of dollars.

The National Medicare Recovery Audit Program was established in 2009. The intent of this program is to identify and correct improper Medicare and Medicaid payments through the detection and collection of overpayments made on claims for health care services provided to Medicare and Medicaid beneficiaries. The frequency and types of audits conducted have increased substantially since 2010. In Fiscal Year 2014, Recovery Auditors collectively identified and corrected 1,117,057 claims that resulted in $2.57 billion dollars in improper payments being corrected and recouped by Medicare.5

After an audit has been conducted and a claim is denied, there are 5 levels of appeal for infusion providers within CMS. Statistics for 2015 from the Office of Medicare Hearing and Appeals (OMHA), give an average time frame of 547 days to reach a Level 3 Administrative Law Judge adjudication, indicating a significant backlog in the current system.6 Since audits are a common occurrence, infusion providers should understand and adhere to Medicare PN policy by collecting necessary qualifying documents prior to discharge which may help to protect the patient financially in the long run.

“Are other medically necessary infusion therapies like hydration and anti-infectives covered by Medicare?”

“How can my patient obtain access to the therapies they need at home if not?”

Challenges with Medicare and Home Infusion Therapies

The Medicare program is the only payer in the United States that fails to recognize the clinical and cost benefits of providing infusion in the home setting. Currently, many infusion therapies are not covered by Medicare under Part B, even when medically necessary (Table 5).

Since Medicare has not kept up with current utilization and nationally accepted standards for use of PN, organizations including the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) and the National Home Infusion Association (NHIA) have lobbied CMS for years in an attempt to change existing law so that meaningful home infusion therapy for Medicare beneficiaries is available. Current policy for HPN severely limits access to therapy with few patients meeting the government’s criteria, either due to the test of permanence required, or non-qualifying conditions for PN such as malnutrition, GI/nutritional complications due to cancer treatments or bariatric surgery.

An abstract published in 2007 reported that only 16% of Medicare PN referrals received (over a large geographically and medically diverse sample) by a national infusion provider met CMS HPN policy requirements for coverage.7 Almost 10 years later, another national infusion provider with similar referral statistics, demonstrated that even fewer Medicare beneficiaries (10.5%) referred for HPN met the restrictive policy requirements, leaving few options for patients without coverage unless they had a secondary major medical insurance policy.8

Transitioning from Commercial Payer to Medicare Coverage-What Then?

A significant challenge for HPN patients, providers, and their physicians is when a patient transitions from a commercial payer to Medicare coverage when they meet disability criteria or turn 65 years old. There is no such thing as “grandfathering” of HPN coverage when a patient flips to Medicare from another insurance company, making it incredibly difficult to meet the stringent rules of Medicare coverage when a patient has already been on HPN for months or even years. There are no clear guidelines from CMS on how to “qualify” patients already on HPN who enroll into the Medicare program, leaving physicians and providers to search and scour through old medical records from the time period when the patient first started on PN (if they even exist) and attempt to qualify them retroactively. Many insurance providers only require a statement of “medical necessity” for HPN coverage; therefore testing, objective studies, and length of need documentation may never have been completed at the time of PN initiation months or years before.

Most commercial payers also do not follow a “permanent impairment” deal breaker for HPN coverage, so documentation required by Medicare when PN was initiated, i.e., a statement of how long the attending physician thought the patient would need HPN, may not exist because the insurance coverage the patient had at the time did not require it. Unfortunately, despite the fact that there is almost always medical necessity for PN, when a patient switches to Medicare, there will be no coverage for the HPN if there is no “qualifying” situation (A-H), the objective evidence is not available to support the qualifying situation, or there is no documented length of need of 90 days or longer, even in cases where a patient has been on HPN for many years.

Healthcare practitioners caring for HPN patients would be well advised to guide their patients to examine all insurance options available regarding original Medicare, Medicare Advantage or replacement plans before dropping existing insurance coverage when they turn 65 years old. Table 6. outlines less than ideal potential options to investigate when there is no coverage under Medicare.

What about Medicare Part D? Is there any coverage for PN or Other Infusion Therapies Needed?

In the above situation, if a patient does not meet Medicare Part B criteria for HPN when they transition to Medicare, the logical assumption would be that the patient is entitled to HPN coverage under Medicare Part D.

Part D is a prescription drug only benefit that may or may not have limited coverage for certain ingredients in the PN, for example those deemed prescription drugs such as amino acid or lipid. Rarely are all (if any) PN ingredients covered under Part D and each Part D provider has a different drug formulary. Since Part D is a prescription drug only benefit, there is no coverage for pump, supplies, tubing, delivery, or clinical management/professional services, making it nearly impossible for any provider to accept Part D reimbursement. Patients will almost always have a considerable co-pay for these necessary supplies if they choose to receive care at home. If additional PN related infusion therapies such as hydration or anti-infectives are prescribed, the same scenario presents a challenge for the practitioner trying to find providers willing to accept Part D reimbursement when much of the therapy cost is not covered.

Hoping for Change? Medicare Site of Care Act S. 275/H.R. 605

The Medicare Home Infusion Site of Care Act of 2015 S. 275/H.R. 605 was introduced by Senators Johnny Isakson (R-GA), Mark Warner (D-VA) and Congressmen Eliot Engle (D-NY) and Pat Tiberi (R- OH). The goal is for Medicare beneficiaries to have access to home infusion. This bill would provide a pathway for reimbursement for professional services, supplies and equipment associated with home infusion therapy under Medicare Part B, enabling the Part D coverage of infusion drugs to become more meaningful for Medicare beneficiaries. The bill also requires development of safety standards to ensure the safe and effective provision of infusion therapy, allowing the Medicare program to realize the efficiencies and positive outcomes the private sector has experienced for over 30 years. If passed, many more patients could receive cost-effective, medically necessary infusion treatments such as PN, hydration and anti-infectives in the home setting.

At present, infusion therapy including PN is fully covered by Medicare everywhere but in the home setting: hospitals, skilled nursing facilities (SNFs), hospital outpatient departments, and physician offices. Medicare may pay a portion of certain infusion drugs provided in the home, but due to the lack of reimbursement for the necessary services, supplies and equipment used in the provision of the infusion therapy, most Medicare beneficiaries in reality do not have access to therapy at home since the cost may be prohibitively expensive for the patient, with copays as high as $30-$80 or more per day. If passed, the Medicare Home Infusion Site of Care Act will provide a much needed mechanism for coverage of all that is necessary to infuse a drug and/or PN safely-clinical professional services, supplies and equipment-which would make the Part D coverage of infusion drugs meaningful and logical.

For more information on how to support the passage of this bill (including templates to write to your state representatives) go to:

• http://www.nhia.org/resource/legislative/ MedicareHomeInfusionSiteofCareAct.cfm

• www.nhia.org/resource/legislative/ WriteYourMemberofCongressMHISOCA.cfm

Selection of HPN/infusion providers who are fluent and compliant with Medicare and federal law may protect beneficiaries from financial hardship down the road. Some providers will accept Medicare PN referrals quickly and without a thorough assessment, then later discontinue care when they learn there is no reimbursement from CMS. If an infusion provider quickly accepts a Medicare PN case without a complete review of the documentation prior to discharge, it should be a red flag to the clinician/referral source. Qualified reputable HPN providers should offer consultative guidance in the way of a “records review” at the time of referral to help physicians navigate the complexity of the policy with the ultimate goal of protecting the patient.

During open enrollment time periods, physicians and PN providers should guide patients to investigate alternative insurance options and/or Medicare Advantage or replacement plans with more meaningful benefits should the patient require PN or other home infusion due to a chronic condition. Lastly, although not ideal, Medicare beneficiaries do have coverage for PN in a skilled nursing facility (with Part A restrictions), so if the HPN did not meet coverage criteria because the length of need was not permanent, the patient may have coverage in the SNF setting.

CONCLUSION

Until new laws are passed and coverage for home infusion/PN becomes more meaningful under Medicare, healthcare providers should carefully assess the need for HPN therapy. Referrals for homecare should be made as early as possible to allow for thorough examination and review of medical documentation and allow for the possibility that additional testing may be required by Medicare. This will help ensure that the beneficiary will have coverage for HPN and is not at risk for denial of payment should an audit determine that coverage criteria was not met, potentially leaving the patient and family with a significant bill in the future.

All providers involved in the care of patients requiring HPN and related therapies should develop a stronger understanding of the Medicare reimbursement system in order to advocate for the needs of this challenging patient population. Failing to do this may prevent patients from having access to life sustaining nutrition support and could also expose them to significant financial harm. Given these risks, clinicians would be well advised to carefully document the clinical necessity of HPN backed up by objective evidence and testing, along with an estimated length of need for the therapy for all patients going home on PN-as if they needed to meet Medicare criteria. Patients who currently have private insurance may eventually transition to Medicare and supporting documentation will be required for a successful transition and continuation of HPN therapy. For more information regarding the Medicare Home Infusion Site of Care Act as well as additional resources, see Table 7.

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COLORECTAL CANCER: REAL PROGRESS IN DIAGNOSIS AND TREATMENT, SERIES #9

Colonic Capsule as a Screening Test for Colorectal Cancer: We are Improving

December 2016 • Volume XL, Issue 12
Cesera Hassan,Nadir Arber

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Colonoscopy is currently the gold standard of colorectal cancer (CRC) screening. The procedure, however, is invasive and is not without its risk of complication, thus diminishing patient participation in effective screening programs.1-3 Additionally, patients are reluctant to undergo screening colonoscopy due to the discomfort and inconvenience of the pre-procedure laxative colonic cleansing as well as the anticipated pain of the procedure.3,4 In an effort to improve patients’ willingness to cooperate in improving their colon health, non-invasive testing of the colon has been trialed over the past few decades. Colonoscopy with colon-capsule is an endoscopic technique developed for a non-invasive, painless exploration of the colon without the need of sedation and injection of air. Its major obstacle is the need for meticulous colonic cleaning. The Check Cap imaging system, which is comprised of an ingestible imaging capsule and an external recorder, is one such device that may overcome the hurdle of pre-procedure bowel preparation. This capsule emits radiological data for constructing three-dimensional images of the colonic mucosa without the need for colonic cleansing. Since the system is safe, easy-to-use, painless, patient-friendly and private, this imaging system may significantly increase participation rates in a CRC screening programs.

Cesera Hassan1 Nadir Arber2 1Endoscopy Unit Nuovo Regina Margherita Hospital, Rome, Italy 2The Integrated Cancer Prevention Center and Department of Gastroenterology, Pathology Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

INTRODUCTION

Colorectal cancer (CRC) is a major health concern with an incidence of 1.2 million new cases per year and a mortality rate close to 600,000 yearly. At the same time, CRC is one of the most preventable and curable malignancies if diagnosed at an early stage.4,5 Consequently, CRC screening programs were established in more than 50 countries.6 Despite participation rates in these programs being below the set targets, CRC incidence and mortality rates are declining.7 Colorectal cancer screening in the United States increased significantly from 2000 to 2010 and was essentially unchanged in 2013. Over the same period, the incidence of and deaths from colon cancer have decreased and these are attributed to improvements in screening for CRC, improved treatment strategies and changing patterns in risk factors.8 Specifically, CRC death rates declined by 2% per year during the 1990s and approximately 3% each year during the past decade (2001-2010) with the most impact in adults aged 65 and older. In Europe, CRC screening programs have been implemented in 19 of 27 European Union (EU) countries with participation rates nearing 60%.9 CRC mortality has fallen in an increasing number of European countries since 1970, despite persistent differences between specific regions in Europe. The largest reductions in CRC mortality have occurred in western and northern European countries because of increased screening participation and improved access to specialized care. In most central European countries, CRC mortality has been stable or slightly decreasing since the early 2000s, but is still increasing in most eastern European countries.10 These epidemiological findings infer that participation in a CRC screening program will culminate in an improved health outcome.11,12

CRC Screening Tests

The American College of Gastroenterology (ACG) has classified colorectal cancer screening tests as either CRC prevention tests or CRC detection tests.13 Tests that are labeled as prevention are “imaging tests” given their potential to identify both cancer and polyps. These tests either enable visual assessment of the structural integrity of the colon and rectum (e.g. flexible sigmoidoscopy, colonoscopy and capsule colonoscopy) or are non-invasive tests that are able to obtain two-and/ or three-dimensional (3D) images of the colon and its mucosa [e.g. computed tomography (CT) colonography and a double-contrast barium enema]. On the other hand, detection tests are “indirect tests” that probe the stool for the presence of markers of CRC [e.g. fecal occult blood test (FOBT), fecal immunochemical test (FIT) and the fecal DNA test)]. While non-invasive, these tests have low sensitivity for detecting polyps. Colonoscopy is the standard of care for evaluating the colon, either as a primary test or as a follow up to an abnormal imaging modality or positive stool testing.13,14 The ACG also recommends that a CRC prevention test, preferably a colonoscopy, be first offered to patients with family history of CRC. Hence, colonoscopy has become an invaluable component of most national screening programs. While the entirety of the colon can be evaluated during colonoscopy and abnormal tissue(s) can be sampled or removed during the procedure, the procedure has disadvantages that may limit its use. Some of these considerations include the need for thorough colonic cleansing, sedation and the potential need to stop taking certain medications (especially anticoagulants) as well as the rare but potentially life- threatening complications of bleeding and perforation. Additionally, colonoscopy is avoided by patients as the procedure elicits feelings of fear, embarrassment, loss of dignity or vulnerability, absence from work, lack of awareness on the importance of screening, transportation difficulties, obstacles with scheduling of appointments and financial cost.6,15

Colonoscopy with Colon-Capsule

In an effort to improve acceptability and safety of lower-GI endoscopy, colonoscopy with colon-capsule (CCE, PillCam Colon, Given Imaging Ltd., Yoqneam, Israel) is an endoscopic technique developed for a non- invasive, painless exploration of the colon without the need of sedation and injection of air.16,17 Initial studies comparing CCE with colonoscopy (traditional and virtual) performed in Israel and Belgium1,18 show that CCE allows direct visualization of the mucosa (such as traditional examination), does not use radiation (such as virtual colonoscopy) and does not cause pain, eliminating the need for sedation.19

Technology

The new generation of CCE (CCE-2) represents a technological evolution of the previous capsule. It measures 11.6 x 31.5 mm. It is equipped with two optical domes with a viewing angle of 172° (the previous version had an angle of 156°), two light sources (one for each optical dome), an antenna that transmits images to an external recorder and a battery (10 hour battery life).20 In addition, CCE-2 owns an advanced system of acquisition and transmission of images. It is in continuous two-way communication with the external data recorder, which is no longer a single recorder of images, but an actual computer. The data recorder receives images from CCE-2, and it processes them to “understand” if the capsule is at rest or in motion and sends signals to the capsule, establishing the speed of acquisition of the images. When the CCE-2 is immobile, it acquires four images per second, however, when it is in motion it acquires 35 images per second.16 The data recorder also assists and guides the patient during the stages of bowel preparation indicating through a sound system and a display how to proceed with the intake of drugs and when the procedure is finished. Unique to this procedure, aside from picking up the CCE-2 from the hospital, the remainder of the testing is performed at home.

Preparation for the Procedure

Bowel preparation for CCE includes the use of laxatives and drugs to activate intestinal peristalsis in order to achieve three objectives: 1) to ensure an adequate level of cleaning, 2) to stimulate the motility for CCE progression and 3) to fill the colon of transparent liquids to adequately distend the bowel. CCE is not able to insufflate air to distend the bowel, or to aspirate any residues, which therefore need to be completely removed through a dedicated preparation.21 The use of drugs stimulating colon motility (usually sodium phosphate or sodium sulfate, more recently) is necessary given minimal colonic peristaltic movements throughout the day. The excretion rate of CCE (about 20%) was too low with the use of traditional colonoscopy preparations.1 Sodium phosphate (NaP) and sodium sulfate result in a strong activation of peristalsis responsible for the CCE progression and excretion, which occurs in 90% of cases within 10 hours of ingestion. Two recent studies with the new generation capsule.16,20 assess a novel bowel preparation involving the use of a split regimen with 4 liters of PEG and a reduced dose of NaP.22 Adequate cleaning has been achieved in 78-81% of patients and CCE excretion (which corresponds to complete colonoscopy) in 81-88% with this preparation.16,20 This new preparation is more tolerable for the patient thus increasing compliance, reduces the NaP which decrease the risk of adverse events and the rate of colon cleansing and excretion of the capsule are encouraging. The Aronchick colon cleansing rating scale is generally utilized to assess the prep (poor, fair, good and excellent) with good inter-observer agreement (kappa = 0.619).17 Although the four-level system has been widely adopted in research, a recent guideline suggests the use of a simplified two-levels scale for clinical activity.

Accuracy of the Capsule

Most of the studies published in the literature center around data obtained with the first generation of CCE. A meta-analysis with the first generation of CCE 23 summarized the preliminary experience. Eight studies with a total 837 patients showed a 71% CCE-sensitivity for polyps of any size and a 68% sensitivity for significant lesions (>6 mm polyps or ≥3 polyps). The specificity for polyps of any size and for significant lesions was 75% and 82%, respectively. Finally, CCE identified 16 of 21 cancerous lesions, showing a sensitivity of 76%.

The second generation of CCE was evaluated in16,20 an Israeli multicenter study and a European multicenter study. Both studies were blinded and compared CCE to conventional colonoscopy with a standardized, split- dose bowel preparation (PEG 2L the day prior to the procedure and 2L the morning of the procedure with a reduced dose of NaP). The prevalence of polyps of any size (in 104 patients, mean age 49.8 years) was 44%, 53% of which were adenomas. (16) CCE sensitivity for polyps ≥6 mm was 89% (95% CI 70%-97%) and 88% (95% CI 56-98) for polyps ≥ 10 mm; specificity was 76% (95% CI 72-78) and 89% (95% CI 86-90), respectively. An adequate level of cleansing was observed in 78% of patients (95% CI 68-86) and CCE colonoscopy was complete (natural excretion of video capsule) within eight hours in 81% of patients.

In the European multicenter study (20), 109 patients were enrolled (mean age 60 years). The sensitivity (“per patient”) of CCE for polyps ≥ 6 mm and ≥ 10 mm was 84% and 88%, with a specificity of 64% and 95%, respectively. All three invasive adenocarcinomas were detected by the capsule. The rate of excretion of the capsule was 88%. Adequate cleansing of the colon was observed in 81% of patients.

Despite only two published studies, some general observations can be made. First, the second-generation capsule has shown a much higher sensitivity for significant lesions compared to the first generation. Secondly, for polyps ≥ 6 mm, the specificity is still sub-optimal. The low specificity is partly due to true polyps ≥ 6 mm that were regarded as false positive because they were missed by colonoscopy, the golden standard in this trial.14,25 Next, the preparation of the new scheme show encouraging results both in terms of quality of cleansing and in terms of completeness of the examination. Finally, CCE is a safe technique without any report of serious adverse events.16,20

Check Cap Capsule

The diagnostic accuracy of colonoscopy is very dependent on the quality of the colonic cleansing.26,27 Inadequate colonic cleansing results in cancellation or rescheduling of the procedure, lessens the procedure’s diagnostic accuracy and discriminative ability, lowers the cecal intubation rates and increases the patient’s discomfort and inconvenience.

The Check Cap Ingestible Imaging Capsule

The Check Cap ingestible imaging capsule (Check Cap, Mount Carmel, Israel), is comprised of a mobile imaging capsule (34 mm x 11.5 mm, 13 grams), which is ingested together with a radiopaque contrast agent by the patient, and a stationary external recorder, which is located in a dermal patch on the patient’s back (Figure 1). The imaging capsule contains three miniaturized systems, an X-ray emitting system, a data acquisition system and a local positioning system (Figure 2).

X-rays from a short-lived radioisotope, housed within a rotating collimator whose rotation is powered by a battery-driven electric motor, are emitted in all directions when the capsule’s position changes. The data acquisition system contains sensors, which can discriminate X-ray fluorescence from ingested radiopaque contrast agent and scattering from the intestinal mucosa. The positioning system uses electromagnetic signals, which are emitted by the capsule and tracked by the dermal patch. Imaging data and position signals are continuously transmitted by telemetry to the external recording unit (Figure 3). The recorder’s data are then uploaded and processed by computer to construct 3D images of the colon’s lumen, structure, and contour.

Human Studies on the Safety and Clinical Utility of the Device

The device’s safety and potential utility were assessed in Germany and Israel at several medical centers.28 In the first section, 75 healthy volunteers aged 41-70 years swallowed dummy capsules. All capsules were retrieved and were undamaged upon inspected. In the second part, 49 capsules were swallowed by 46 volunteers aged 45- 68 years (three patients swallowed the capsule on two different occasions). During this study, a lightweight external recording unit was strapped to the waist of each participant while normal daily routine was maintained. After ingesting the capsule, each participant drank 50- 70 ml of an iodine-based contrast agent daily until the capsule was eliminated. Forty-eight of the 49 capsules were ingested, transited the gastrointestinal tract and were naturally eliminated without any adverse effects. The missing capsule was retrieved from the cecum of an asymptomatic patient during a scheduled colonoscopy for a planned polypectomy. The average radiation dose to each volunteer was 0.03±0.0007 mSv, which is less than the amount of radiation exposure from one chest X-ray. (Figure 4) The 3D images revealed the typical structure and contour of the different colonic segments, such as the hepatic flexure and the triangular shape of the transverse colon. Polyps in several patients were detected by the device and their presence was later validated by colonoscopy. (Figures 5,6)

Beebe and his colleagues.29 investigated whether removal of a laxative preparation would improve CRC screening rates using data that were collected from a mixed-mode and telephone survey. They reported that removing this relatively common disincentive to CRC screening participation can potentially increase patient receptivity to CT colonography. As such, the Check Cap Capsule system could be an alternative method of CRC testing.This imaging system is a safe, easy-to-use, patient-friendly, painless, and private medical device with high diagnostic accuracy discriminating patients with disease from those without disease without the need for a bowel preparation. Another advantage of the system is that the dose of ionizing radiation to the patient is lower not only than that of CT colonography but also less than chest X-ray. (Figure 4) Additionally, use of this concealed imaging system eliminates the need to schedule an appointment at a health facility, be absent from work and enables the patient to continue their daily routine without the negative emotional and physical feelings which may be experienced during colonoscopy. For all of these reasons, this innovative imaging system could potentially increase participation rates in a local and/or national CRC screening program.30 Many features of image reconstruction and measurement of polyp size and colon diameter still need refinement and validation. To resolve these issues, modifications to the imaging capsule are on going and international, randomized, multicenter studies are planned for the end of 2016.

CONCLUSION

While colonoscopy is currently the most utilized and accepted form of colorectal cancer screening, technology has allowed inroads to developing new testing that may improve patient care. Colonic capsules are safe novel systems that are easy-to-use, painless, patient-friendly and private. These devices should significantly increase participation rates in a CRC screening programs.

Acknowledgement

The authors wish to thank Dr. Arieh Bomzon, Consulwrite (consulwrite.com) for his editorial assistance in preparing this manuscript.

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Gastrointestinal Motility And Functional Bowel Disorders, Series #20

Current Treatment Strategies for Irritable Bowel Syndrome

November 2016 • Volume XL, Issue 11
Pratik Naik,Richard W. McCallum

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Irritable bowel syndrome (IBS) is a functional bowel disorder which affects 11% of the world’s population. IBS is accompanied by significant socioeconomic burden, and a lack of recognition of the condition leads to many patients left undiagnosed. The pathophysiology of IBS is not well understood but new concepts are emerging. Treatment of irritable bowel has always been challenging and focuses on addressing abnormal stool frequency, abdominal pain and the psychological state. In this article, we provide an update on IBS therapies newly approved by the Food and Drug Administration (FDA), suggest strategies for incorporating the spectrum of the medications that are already being utilized for specific IBS patient settings and also preview new therapeutic directions.

Pratik Naik, MD, GI Motility Fellow and Richard W. McCallum MD, FACP, FRACP, FACG, AGAF, Founding Chair, Department of Medicine, Director, Center for Neurogastroenterology and GI Motility, Texas Tech University, Paul L. Foster School of Medicine El Paso, TX

INTRODUCTION

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain associated with a change in bowel habit. More specifically, the Rome IV criteria for IBS state that patients should have recurrent abdominal pain for at least one day a week in the last three months associated with at least two of the following: pain related to defecation, onset of pain associated with a change in frequency of stool or onset of pain associated with a change in form of stool (Bristol stool scale criteria).1 These symptoms must be present for at least six months before diagnosis, however they may be present for years prior to the patient’s initial evaluation. Additionally, clinical criteria, such as symptoms exacerbated by stress, symptoms occurring during the day and not while asleep, incomplete evacuation and bloating and distension, can be utilized in making the diagnosis of IBS.

In the United States, the prevalence of IBS approaches 16% (45 million) of which 70-80% are women.2,3 IBS can be diagnosed in all age groups4 however roughly 50% of patients with IBS report their first symptoms before the age of 35 years.5 These symptoms affect quality of life and the patients have many absences from work.3 However, there is a lack of recognition of the condition and up to 75% of patients either do not seek medical attention or are not formally diagnosed.2 There are often concomitant entities, specifically fibromyalgia, chronic fatigue syndrome, chronic migraine headache, interstitial cystitis and temporomandibular joint dysfunction, that can co-exist in half of IBS patients and provide a clinical clue to consider IBS as an underlying diagnosis.6,7

Improving a patient’s quality of life is the mainstay of treatment. Establishing physician rapport, patient education on IBS and empowering them to accept some responsibility for their care are key as well. Non- pharmacological approaches such as stress management, psychotherapy, behavioral modifications and focus on diet have been shown to improve symptoms and should be sustained long term. In this article we describe the new IBS therapies as well as suggest strategies for incorporating them into the spectrum of the medications that already have been shown to be useful and focus on specific patient challenges.

IBS with Diarrhea (IBS-D)

IBS-D accounts for approximately one third of all IBS patients and affects roughly the same number of men and women. Anti-diarrheal agents such as loperamide, in previous randomized controlled trials (RCTs), have failed to demonstrate benefit in relieving global symptoms of IBS, specifically the abdominal pain.8,9 However, the fear of fecal incontinence accompanying the urgency of the diarrhea means that loperamide can be efficacious for reducing stool frequency in specific settings such as maintaining daily work schedules, traveling, social outing and stressful events.10

Available New Therapies for IBS-D Rifaximin (Xifaxin)

The FDA approved rifaximin for treatment of IBS-D in May, 2015. Rifaximin is a minimally absorbed antibiotic whose mechanism of action is inhibiting bacterial protein synthesis and modulation of intestinal microbiota that are contributing to a microscopic inflammatory process in the bowel.11 There were two TARGET (Targeted non-systemic Antibiotic Rifaximin Gut selective Evaluation Treatment of non-constipated IBS) studies where patients were treated with rifaximin 550mg three times daily for 14 days vs. placebo and followed for a 10 week treatment-free observation period. The primary endpoint was adequate relief of IBS signs and symptoms. This was accomplished significantly more in the rifaximin group than in the placebo group during the four weeks of observation after treatment in the two studies combined (40.7% vs. 31.7%, P<0.001). In an assessment of the composite end point of abdominal pain or discomfort and loose or watery stools, significantly more patients in the rifaximin group than in the placebo group had relief during the evaluation period (46.6% vs. 38.5%, P=0.04, in TARGET 1; 46.7% vs. 36.3%, P=0.008, in TARGET 2).12 Since IBS is a chronic disease, assuming that only two weeks of therapy is going to produce sustained symptom relief was a concern raised by the FDA ultimately leading to an additional study aptly called TARGET 3. In this trial, 2579 patients initially treated with open labeled rifaximin were then followed for 18 weeks and patients received re-treatment in a double blinded fashion if they relapsed. Here, the 636 patients who experienced recurrent IBS symptoms were randomized to receive rifaximin 550mg TID vs. placebo for two weeks followed by a four week treatment-free observation period. The percentage of responders in the retreatment phase was again statistically significant for rifaximin 550 mg vs. placebo-treated patients (37% vs. 29%, p=0.04).12

The adverse events observed during these trials, nausea (3%) and elevated alanine aminotransferase (2%), were infrequent.13 There was no increased risk of infections, including Clostridium difficile infection, and no substantial differences in any adverse events vs. placebo.14 The FDA recommends evaluation for C. difficile if there is no improvement or worsening of diarrhea after treatment with rifaximin and cautions use in patients with severe liver impairment (Child- Pugh Class C) or with concomitant administration of drugs that are P-glycoprotein (P-gp) inhibitors (e.g. cyclosporine) due to increased systemic exposure to rifaximin.13

Eluxadoline (Viberzi)

The FDA approved eluxadoline for treatment of IBS-D in May, 2015. Eluxadoline is a µ and k-opioid receptor agonist and δ-opioid receptor antagonist and has minimal absorption. This agent binds to peripheral opioid receptors in the gastrointestinal (GI) tract resulting in slowing of GI motility and decreasing gut secretions. However, an additional unexpected mechanism was recognized. Eluxadoline was shown to decrease the sensitivity of afferent neurons (in the submucosa) to pain thus reducing visceral hypersensitivity, a local gut effect, with no central nervous system (CNS) involvement.16,17 Two double-blinded, placebo-controlled clinical trials were conducted in which 2,427 patients were randomly assigned to receive eluxadoline (at 75 mg or 100 mg) or placebo twice daily (BID) for 26 weeks in both studies. Significantly more patients treated with eluxadoline 100 mg BID vs. placebo (33% vs. 20 %; p< 0.001) experienced improvements in diarrhea and abdominal pain for at least 50% of the trial period. This response was noted within the first week of initiating therapy.17

The most common side effects were constipation (8% vs 3% placebo), nausea (7% vs 5%) and abdominal pain (7% vs 4%). Upper abdominal pain attributed to sphincter of Oddi spasm was observed in 0.8% of the patients and was more likely to occur in patients with prior cholecystectomy. The presence of opioid receptors in the sphincter of Oddi could contribute to this observation. These symptoms were usually induced within the first two weeks of treatment and resolved upon discontinuation of the drug.17 In addition, there was a rare occurrence of pancreatitis (less than 0.3%) not associated with sphincter of Oddi spasm and the majority of cases were related to excessive alcohol use. Because of this finding it is recommended that patients with history of chronic pancreatitis or currently consuming at least three or more alcoholic beverages daily do not receive this agent.16

The current recommended dose for eluxadoline is 100mg twice daily. The reduced dose, 75 mg twice daily, is initially appropriate for patients post cholecystectomy, those who were not able to tolerate the 100 mg dose, who are receiving concomitant OATP1B1 inhibitors (e.g. cyclosporine and gemfibrozil) or who have mild to moderate hepatic impairment. The use of this agent is not recommended if there is suspected mechanical gastrointestinal obstruction or severe liver impairment (Child-Pugh Class C).16

Alosetron (Lotronex)

Alosetron, a selective 5-HT3 antagonist, was initially approved by the FDA in 2000 for the treatment of IBS-D in women only. Activation of 5-HT3 receptors leads to neuronal depolarization in enteric neurons which reduces visceral pain as well as colonic transit and inhibits GI secretions.18 The drug was later withdrawn due to the serious adverse event of ischemic colitis (IC) and constipation. It was reintroduced in 2002 by FDA under a risk management program with a reduced dose (0.5-1 mg BID) for treatment of IBS-D in women only who were not responding to standard therapies.19

In randomized controlled trials (RCTs), alosetron improved abdominal pain and IBS-related global symptoms compared to placebo.20 Post-marketing safety of alosetron under the risk management program (2002- 2011) reported a low incidence of serious complication of constipation (0.25 cases/1000 patient-years) and ischemic colitis (1.0 case/1000 patient-years).19 Constipation was dose dependent and noted in 29% of patients receiving the 1 mg BID dose compared to 11% in the 0.5 mg dose. The overall incidence of serious constipation was higher in elderly patients or patients taking additional medications that decrease GI motility. Alosetron should be discontinued in patients who develop constipation and it can be restarted under supervision of a prescriber after constipation resolves.25 Alosetron should not be used in patients with history or have high risk for IC. It is also contraindicated in patients with suspected intestinal obstruction, inflammatory bowel disease (IBD), diverticulitis and severe hepatic dysfunction (Child- Pugh Class C).21

IBS with Constipation (IBS-C)

IBS-C accounts for approximately one third of all IBS patients. Over the counter laxatives [polyethylene glycol (Miralax) and bisacodyl (Dulcolax)] can be useful short term in management of constipation in improving stool frequency. However, this type of long- term management does not provide adequate pain relief.

Available New Therapies for IBS-C
Linaclotide (Linzess)

Linaclotide has been approved to treat IBS-C and chronic idiopathic constipation since 2012. Linaclotide, a guanylate cyclase C (GC-C) receptor agonist, induces an increase in both intracellular and extracellular concentrations of cyclic GMP which stimulates secretion of chloride and bicarbonate into intestinal lumen by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. This increases fluid in the intestine leading to an acceleration of colonic transit.22 Based on data from animal models, linaclotide also was able to decrease abdominal pain through effects on afferent neurons in the gut wall.22,23 In two phase III multicenter placebo- controlled RCTs, linaclotide significantly increased the frequency of complete spontaneous bowel movements and reduced abdominal pain for at least six of the 12 weeks compared to placebo (Trial 1: 33.6% vs 21%; Trial 2: 33.7% vs 13.9%).24,25 In all three multicenter placebo-controlled RCTs, linaclotide was shown to be effective in reducing global symptoms of IBS-C.20

Linaclotide 290 mcg is taken once a day on an empty stomach for treatment of IBS-C. Recently a new formulation allows the capsule to be ground and given as a powder with apple sauce orally or through a feeding tube if swallowing problems are present. Diarrhea (20% vs 3% placebo) was the most common adverse reaction noted in trials. Severe diarrhea was reported in 2% compared to less than 1% in placebo group, and diarrhea resulting in discontinuation was 5% vs <1%. The majority of reported cases of diarrhea started within the first two weeks of the treatment and reduced with time.22 Patients with known or suspected mechanical gastrointestinal obstruction or sudden change in clinical states are not appropriate candidates nor should the drug should be used in patients 17 years of age and younger.23

Lubiprostone (Amitiza)

Lubiprostone (Amitiza) 8 mcg BID was approved by the FDA in 2008 for the treatment of women with IBS-C. It activates type 2 chloride channels in small intestinal cells that promote chloride secretion in intestine.26 These secretions soften the stool and increase colonic transit time, which promotes more complete spontaneous bowel movements. In two phase three RCTs, the percentage of overall responders based on patient-rated assessments of IBS-C symptoms was significantly more in patients treated with lubiprostone 8 mcg twice daily compared to those treated with placebo (17.9% vs. 10.1%, p=0.001).27 The most frequent adverse events were nausea (8% vs 4%) and diarrhea (7% vs 4%). Long term safety, 36 weeks, and tolerability were assessed in an additional study; while not placebo controlled, 41% of patients dropped out due to lack of efficacy.28

Treatment Option for IBS-M

The prevalence of IBS-M is equal in both male and female. Abdominal pain remains a challenge for these patients and anticholinergics have been heavily utilized in their management. Hyoscamine, dicyclomine and chlordiazepoxide/clidinium bromide (Librax) are widely used to alleviate abdominal spasms and cramps associated with IBS as well as deceases GI motility and hypersensitivity.29 Previous studies have shown limited evidence regarding long term efficacy in reducing global IBS symptoms and abdominal pain.20 The most common side effects are anhidrosis, blurred vision, confusion, constipation, urinary retention, xerostomia and drowsiness attributed to anticholinergic effects.18,20

Available New Therapies for IBS-M
IBgard (Peppermint Oil)

IBgard, purified peppermint oil, reduces lower GI tract and colon motility by acting on intestinal calcium channels to relax smooth muscle within the GI tract.30 It is a enteric-coated preparation permitting it to bypass the stomach and delivers peppermint oil to the small bowel allowing its effect to be maximal on the lower GI tract.31 In a placebo-controlled, double-blinded RCT, 72 patients who met the Rome III criteria for IBS-M and IBS-D were randomized to receive IBgard 180mg TID vs placebo for 4 weeks. There was a significant reduction in the number of severe or unbearable IBS symptoms vs placebo (66% vs 42%, P=0.02) and reduction in severe or unbearable abdominal pain intensity vs placebo (79.4% vs 40.5%, P=0.01). The study also showed improvement in IBS global symptoms.32 The mechanism of action, particularly for reducing pain, remains poorly defined.

Peppermint oil can also relax the lower esophageal sphincter, which can lead to symptoms of acid reflux when taken orally.31 Enteric-coated preparations can eliminate this side effect. IBgard is an OTC medication; however, it should be used under physician supervision. It is not recommended in patients with IBS-C since constipation may be worsened.

Suggested Strategic Approaches Based on These New Therapies in IBS-D

1. Choice of Rifaximin

Rifaximin may be considered as a reasonable treatment of choice in the following clinical settings:

  • A patient with suspected post infectious (PI) IBS-D based on a very suggestive history of food poisoning, travel, military deployments etc.
  • Patients where the IBS presentation has been relatively short (< 5 years) with or without a typical post infection history.
  • Patients over 50 years of age where onset has been recent, this suggesting a higher likelihood for PI- IBS even when no specific event can be recalled.
  • Patients with IBS-D where gas, bloating and postprandial abdominal distension are prevalent suggesting a component of small intestine bacterial overgrowth (SIBO) as a manifestation of a recent GI infection or change in microbiota.

Rifaximin is not a stand-alone therapy. Patients seeing a gastroenterologist may already be following a low FODMAP (fermentable oligo-di-monosaccharide and polyol) diet and antidepressants but still have remaining symptoms. Here a course of rifaximin is a reasonable step in addition to the medications being received. Since it is a two-week regimen, there will be evidence for improvement within a short time.

Questions Remaining Regarding Rifaximin

  • How does one can explain the improvements in the abdominal pain with rifaximin when the rationale for its use is modulating microbiota? The current rationale is that its anti-inflammatory effects reduce microscopic inflammation in the gut wall including improving the concept of “leaky cell junctions”, although there is no clear evidence of this to date.
  • Can two weeks of therapy sustain the reduction in abdominal pain? The FDA approval for rifaximin does allow for two more re-treatments to be given over time. The timing of the re-treatment course has been vague. The follow up in clinical trials was approximately five months so one could infer that re-treatment may be considered during that time frame for that subset of patients who initially achieved improvement and relapsed.
  • Will other agents be required to address pain relapses over greater time periods? Here there could be a role for antispasmodics as needed as well as assessing a role for tricyclic antidepressants in obvious stress related settings
  • Should patients completing a course of rifaximin then start probiotics in order to sustain a better microbiota environment? This has not been addressed in a study format. If gas and bloating were the deciding factors to initiate rifaximin initially then follow up probiotics seems reasonable
  • Can there be a profile of the best candidate? For the future, stool analysis of gut microbiota by polymerase chain reaction (PCR) may define particular subtypes who can be shown to be the best responders. This may be particularly relevant to explain a subset where effective pain reduction is being sustained.

2. Choice of Eluxadoline

The primary choice of eluxadoline may be considered in the following clinical settings:

  • Patients with IBS-D whose predominant symptoms are stool urgency and fear of having a “bowel accident” or actually experiencing intermittent fecal incontinence. The activation of opioid receptors in the gut wall makes sense in decreasing stool volume and transit as well as secretions. This is particularly relevant to morning diarrhea preventing timely arrival at work or leaving the home.
  • A history of chronicity (>5 years) would all favor eluxadoline since long term use has been studied (at least 1 year) and the FDA approval is also for chronic use since there was also an excellent safety profile.
  • Treatment with eluxadoline does not preclude concomitant therapies e.g. antidepressants, low FODMAP diets and addressing excessive bloating and gas to address the “peaks and valleys” during the course of chronic IBS where treatment with eluxadoline may be for months or years.

Questions Remaining Regarding Eluxadoline

There is a pressing need to clarify how the interactions of eluxadoline as an agonist of mu and kappa receptors and at the same time antagonizing delta receptors leads to decreased pain via afferent submucosal neurons. The role of kappa receptors still remains to be studied.

3. Choice of Alosetron

Alosetron could be a preferred consideration only in women with IBS-D where the diarrhea is such that bowel movements and stool urgency with possible fecal incontinence are frequent and who have failed all other management strategies. As a part of a risk evaluation and mitigation strategy, patients and prescribers are required to enroll in a prescribing program and medication guide should be provided with each prescription.

Suggested Strategic Approaches Based on New Therapies in IBS-C
1. Choice of Linaclotide

Linaclotide should be considered as a treatment of choice in patients with predominant symptoms of constipation and abdominal pain. There are two main challenges:

  • The effects of the medication on abdominal pain can take up to 10 weeks to fully maximize presenting a challenge to keep patients motivated to take the medication with the possibility that a suboptimal pain relief will result. Anticholinergics may be needed as adjuncts to address pain during this time. A short acting agent such as hyoscyamine is preferred since long acting agents such as dicyclomine, librax and donnatal (belladonna alkaloids, phenobarbital) may worsen constipation. The good news for the patients is that increased frequency of stools occurs in the first 48 hours indicating to the patients that the drug is working (they are responders) and hence there is a high likelihood that abdominal pain relief should follow over the next few weeks
  • Initial diarrhea can be prominent and although the 290 mcg dose is recommended in IBS-C to achieve the long-term pain benefits, starting at 145 mcg and building up to 290 mcg will overcome the concern that diarrhea may result in a patient prematurely stopping the agent. An alternative strategy is to use 290 mcg every other day until the bowel adapts to the increase in luminal fluid and diarrhea is not a concern. This usually occurs over two to three weeks and then daily dosing can be initiated.

2. Choice of Lubiprostone

Lubiprostone was associated with mild to moderate nausea and vomiting (11%) which could be major limiting factor as well as the BID dosing and also the fact that it was only approved in women. There is also lack of evidence for long term safety and tolerability because the previous long term study had a high dropout rate (41%). Recently, Amitiza 24ug BID has been approved for opioid induced constipation. Hence in IBS patients taking opioids for other reasons e.g. back pain, neuropathy or headache, this high dose can be considered.

Strategies Approaches Based on These New Therapies in IBS-M
1. Choice of IBgard

IBgard is an OTC medication is only intended for use in D and IBS-M. It can be used as a short term adjunct when abdominal pain, spasm and discomfort are the main symptoms. However, more definition is required of the mechanism of action regarding reducing abdominal pain which is thought to be more colonic in origin yet the agent is largely presented to the small bowel. More RCTs are needed to evaluated long tern efficacy and tolerability. IBgard is an OTC medication but it should be taken under physician supervision.

Future Therapy Approaches

Role of Methanogens and Methane in IBS-C

Recently data has suggested an association of methane production with chronic constipation and IBS-D. The proposed mechanism is based on an animal model where methane was found to act as a neuromuscular transmitter and delayed intestinal transit.33 Methanogens such as Methaninobrevibacter smithii have been found to have 80% – 100% colonization rate of the human colon by PCR techniques.34

In a study by Pimentel et al., methane production from a lactulose breath test showed 100% association with IBS-C patients and the prevalence of methane positivity was very low among patients with IBD and IBS-D. In that study, higher constipation severity scores were reported by subjects who produced methane.35 However, this association with constipation is unclear as up to 50% of healthy individuals have been reported to be methane formers.34 In addition, relying on the lactulose breath test is a major flaw since it is actually measuring colonic flora and not the small bowel flora as first assumed.

In a retrospective study, rifaximin and neomycin have shown promising results on methane eradication as measured by the breath test. Pharmacotherapy such as chloro/fluoromethanes, 2-bromo- and 2-chloro-ethane sulfonates also have been shown to block key reactions leading to methane biosynthesis. In a phase two trial, a modified-release formulation of lovastain lactone (SYN-010) was shown to act primarily in the intestinal lumen and reduced methane production by M. smithii with minimal impact on gut microbiome.36

Better understanding regarding the role of SIBO and microbiota in IBS patients is needed. Recent studies have demonstrated the utility of sampling small bowel contents and using PCR techniques in identifying differences in gut flora of IBS patients, specifically different phyla compared to healthy individuals. By using these techniques in the future, we may be able to identify subgroups of IBS patients who can be considered the most likely responders to targeted therapies.

Bile Acid Malabsorption

Bile acids (BA) are produced in the liver and have major roles in the absorption of lipids in the small intestine. Bile acid malabsorption (BAM) is estimated to occur in one third of the patients with IBS-D and up to 50% of the patients with functional diarrhea. SeHCAT (23-seleno-25-homotaurocholic acid, selenium homocholic acid taurine, or tauroselcholic acid) is a test used to diagnose BAM. This test is done by measuring retention of the SeHCAT by external scintigraphy one week after administration of a gamma- emitting synthetic bile acid and less that 15% retention after seven days is considered abnormal. In a systemic review in patients with IBD-D, BAM was noted as severe in 10%, moderate in 32% and mild in 26%.37 The bile acid binder cholestyramine has been shown to improve BAM and potentially reduce diarrhea.

TAKE HOME MESSEGES

In this article we review current pharmacotherapy for all IBS subtypes. Treating IBS remains daunting for clinicians: abdominal pain and abnormal bowel function are dual challenges. In fact the statement is often made that the true measure of the skill of a gastroenterologist is how well he or she can treat patients with IBS in their practice. This article emphasizes the background and evidence for new pharmacotherapies now available to practicing gastroenterologists and primary care physicians and also proposes treatment strategies in specific patient settings. It also reminds us that IBS is a chronic entity and our goals are to minimize bad days and maximize good days and improve quality of life. Physician rapport and trust is key. It all begins with actually telling patients their diagnosis: you have irritable bowel syndrome. There are no stand- alone approaches. Current therapies as well as the new agents reviewed are integrated into the setting of addressing stress with antidepressants (e.g. tricyclics), psychological counseling and holistic approaches including relaxation techniques while always focusing on the role of diet. Evolving therapies and concepts regarding biomarkers particularly related to bile acid malabsorption and changes in gut microbiota specifically methanogens are also reviewed. The future will be more targeted therapies but this will also rely on unraveling an entity which will remain poorly understood until the big umbrella term of “IBS” can be replaced by describing entities based on specific mechanisms and pathology.

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Nutrition Issues In Gastroenterology, Series #157

Achalasia And Nutrition: Is it Simple Physics or Biology?

November 2016 • Volume XL, Issue 11
Dhyanesh A. Patel,Michael F. Vaezi

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Achalasia is one of the most studied motility disorders of the esophagus and delay in diagnosis can result in significant patient morbidity and impaired quality of life. Esophagogastroduodenoscopy is necessary to rule out potential malignancy that can mimic achalasia. Although there are no curative therapies currently, excellent palliation of symptoms can be achieved in &lt;90% of patients with the use of graded pneumatic dilatation, surgical myotomy or per-oral endoscopic myotomy. This article briefly discusses the clinical presentation, diagnosis, and management options in patients with achalasia followed by insights into nutritional implications that are often neglected.

Achalasia is one of the most studied motility disorders of the esophagus. Patients often present with dysphagia, regurgitation and varying degrees of weight loss. Delay in diagnosis can result in significant patient morbidity and impaired quality of life. The diagnosis is made based on clinical history and esophageal high resolution motility testing. Esophagogastroduodenoscopy is necessary to rule out potential malignancy that can mimic achalasia. Although there are no curative therapies currently, excellent palliation of symptoms can be achieved in >90% of patients with the use of graded pneumatic dilatation, surgical myotomy or per-oral endoscopic myotomy. This article briefly discusses the clinical presentation, diagnosis, and management options in patients with achalasia followed by insights into nutritional implications that are often neglected.

Dhyanesh A. Patel, MD and Michael F. Vaezi, MD, PhD, MSc (Epi), FACG, Professor of Medicine, Clinical Director, Division of Gastroenterology, Hepatology and Nutrition Director, Center for Swallowing and Esophageal Disorders. Division of Gastroenterology, Hepatology and Nutrition. Vanderbilt University Medical Center, Nashville, TN

INTRODUCTION

Achalasia is a rare esophageal motility disorder that is characterized manometrically by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter (LES) in response to deglutition. Thus, primary symptoms at presentation include dysphagia and regurgitation of undigested food with varying degrees of weight loss.1 Achalasia was first described by Sir Thomas Willis in 1674 with recent evidence suggesting an annual incidence and prevalence of approximately 2/100,000 and 10/100,000 respectively.2,3 The disease can occur at any age, but is usually diagnosed between 30 and 60 years with a mean age at diagnosis of > 50 years.4

The underlying etiology of achalasia is loss of myenteric neurons that coordinate esophageal peristalsis and LES relaxation. Despite its initial description in 1674, the inciting event that leads to loss of these inhibitory neurons is still unclear.1 Thus, the most common form of achalasia is idiopathic achalasia. However, approximately 2-4% of patients with suspected achalasia have pseudoachalasia (due to malignancies or secondary achalasia from extrinsic processes such as prior tight fundoplication).5 Similar clinical presentation can also occur with other diseases (see Table 1).6

In this review article, we provide a brief overview of the clinical presentation, diagnosis, and management options in patients with achalasia followed by a detailed review of nutritional aspects that are often overlooked in these patients.

CLINICAL PRESENTATION

Patients with achalasia exhibit a varied clinical presentation, however, progressive dysphagia to solids followed by liquids is usually the first clinical symptom.7 Other symptoms include regurgitation that is often non-responsive to adequate proton pump inhibitor (PPI) trial, weight loss, chest pain, and respiratory symptoms (cough, hoarseness, shortness of breath, and sore throat).1 Table 2 shows the most common symptoms in patients with achalasia and their prevalence based on available data. Chest pain is more frequent in younger female patients. Although achalasia as a disease entity overall is rare, it is important for primary care providers to have a low clinical threshold for referral to specialists given that in early stages of the disease, dysphagia may be very subtle and can be misinterpreted as dyspepsia or poor gastric emptying. In addition, these patients will often have heartburn due to food stasis and can lead to an erroneous diagnosis of gastro-esophageal reflux disease (GERD), which is often unresponsive to PPI therapy, and might result in inappropriate referral for anti-reflux surgery (which would significantly exacerbate the underlying problem). Weight loss in these patients is also widely variable with average loss of 20 ± 16 lbs; it is unclear why certain patients with achalasia lose significantly more weight compared to others.8

DIAGNOSIS

The diagnosis of achalasia can be relatively straightforward with a well-documented clinical history, radiography/endoscopy, and esophageal motility testing. Manometry is the gold standard diagnostic test for establishing the diagnosis of achalasia and can also help characterize motor patterns with treatment outcome implications. It is required regardless of findings on barium esophagram and esophagogastroduodenoscopy (EGD). Table 3 identifies the advantages and disadvantages of the various methods used in diagnosing achalasia.

Esophageal Manometry

Characteristic findings for achalasia on conventional manometry is absence of esophageal peristalsis and incomplete LES relaxation on deglutition (usually residual pressures of >10mmHg).1 However, most academic centers have now replaced conventional manometry with high-resolution manometry (HRM) with esophageal pressure topography (EPT), which allows for improvement in pressure sensing technology. This has allowed clinicians to develop a sub- classification of achalasia into 3 clinical groups based on the pattern of esophageal contractility:

• Type I (classic achalasia; quiescent esophageal body)
• Type II (isobaric pan-esophageal pressurization)
• Type III (simultaneous contractions)

Three retrospective studies have showed treatment outcome implications based on the subtype of achalasia suggesting type II having the best prognosis, followed by subtype I; subtype III can be difficult to treat.9-11

Endoscopy

All patients with suspected achalasia are recommended to have an upper endoscopy to exclude mechanical obstruction or pseudoachalasia that can mimic achalasia. At endoscopy, the esophageal body usually appears normal or can be dilated, but can occasionally have friable mucosa with even superficial ulcers secondary to chronic stasis or candida esophagitis.1 The LES is closed even with insufflations of air, showing the appearance of puckering, but the endoscope can pass this area with gentle pressure. If there is high concern for malignancy due to rapid progression of symptoms, biopsies and endoscopic ultrasound or chest CT are obligatory.

Barium Esophagram

Barium esophagram is a non-invasive test for examination of the esophagus that, although less sensitive compared to manometry, can still provide important clinical information with ruling out structural abnormalities and estimating the diameter of the esophagus. Typical findings in achalasia is the presence of smooth tapering of the lower esophagus leading to a closed LES, resembling a “bird’s beak” as showed in Figure 1.1 In more advanced stages of the disease, it can also show a “mega-esophagus,” with massive dilatation of the esophageal body, which can have significant implications for treatment.12 Furthermore, in 1997, de Oliverira et al. described timed barium esophagram with films taken at 1, 2, and 5 minutes after the last swallow of barium for evaluating esophageal emptying in patients with achalasia.13 This and subsequent studies found that the rate of barium emptying was predictive of long term success after treatment.14

MANAGEMENT

Treatment for achalasia is aimed towards palliation of symptoms, as there are no curative therapies for achalasia at present. The goal of management is to reduce LES pressure to allow adequate esophageal emptying and prevent late complications of the disease such as severe malnutrition and recurrent aspiration pneumonia. Current therapeutic options include pharmacologic treatment, pneumatic dilatation, surgical myotomy and more recently per-oral endoscopic myotomy (POEM). We briefly review these options below.

Pharmacologic Treatment

Pharmacological therapy is primarily aimed at lowering LES pressure. Two of the most common agents are calcium channel blockers and nitrates.15,16 These medications can decrease LES pressure by 47-64%, but are often limited due to their adverse effects including headaches, orthostatic hypotension, and edema.17 In a study comparing the effect of sublingual nifedipine to sublingual isosorbide dinitrate, both drugs decreased LES pressure, but the effect of nitrate was slightly better than that of nifedipine (65% vs. 49%, respectively).16 However, patients often develop tachyphylaxis and will lose response to these medications after short-term benefit. Thus, these treatment options are reserved for patients:

1. As bridge to more effective therapy
2. Who have failed botulinum toxin injections
3. Who are not candidates for pneumatic
dilatation or surgery.

Another pharmacologic option is injection of botulinum toxin into the muscle of the LES, which blocks acetylcholine release from nerve endings temporarily causing chemical denervation resulting in increased relaxation. It is highly effective with initial symptom relief in >75% of patients, but the effect wears off over time. Approximately 50% of patients require repeat injections at 6 to 24 month intervals; repeated injections can be progressively less effective.18 In addition, repeated injections into the LES have been shown to make subsequent Heller myotomy more challenging, and thus, are rarely used as a first-line therapy and is primarily reserved for patients who are not candidates for more definitive therapy.19 Table 4 shows pharmacologic therapies that have been shown to lower the LES pressure.

Pneumatic Dilation

Pneumatic dilatation (PD) involves use of a rigid balloon that is positioned across the lower esophageal sphincter with or without fluoroscopy with the goal of disrupting the circular muscle fibers of the LES (Figure 2). The most commonly used balloon is the Rigiflex dilator, which comes in three different diameters (3.0, 3.5, and 4.0 cm). Multiple randomized controlled trials have shown efficacy from 62-90% and is arguably the most effective non-surgical treatment option in these patients.20, 21 It is also very well tolerated with a recent systematic review concluding that using modern technique, the risk of perforation was < 1% and comparable to the risk of perforation during Heller myotomy.22 Predictors of favorable clinical response to PD include older age (>45 years), female gender, narrow esophagus, LES pressure after dilation of <10 mmHg, and type II pattern on high-resolution manometry (HRM).

Surgical Myotomy

Laparoscopic Heller myotomy (HM) combined with an antireflux fundoplication (Dor vs. posterior Toupet) is also a highly effective treatment option with studies showing efficacy rates in the 88-95% range.20,21 Although laparoscopic HM is superior to a single pneumatic dilatation in terms of efficacy and durability, the difference is significantly less when compared with a graded approach to pneumatic dilation using repeated dilatations.23 Thus, pneumatic dilatation and surgical myotomy should both be offered to low surgical risk patients as the initial therapy. Surgery might have a more favorable clinical response in younger male patients or patients with tortuous esophagus, esophageal diverticula or previous surgery on the gastroesophageal junction.1

Per-Oral Endoscopic Myotomy

Per-oral endoscopic myotomy (POEM) is the newest treatment option available at some centers and consists of an endoscopic approach to esophagomyotomy. It involves creating a submucosal tunnel through an esophageal mucosal incision approximately 10cm proximal to esophagogastric junction and then dissecting the muscle fibers beginning at 3cm distal to the mucosal entry site and extending 2cm in to the cardia.24 Treatment success has been reported as high as 90% with significant decreases in LES pressure with improved quality of life measurements and low complication rates.25 There have been no randomized trials comparing PD to laparoscopic HM to POEM and long term outcomes after POEM still need to be studied.

ACHALASIA AND NUTRITION

Weight Loss: Is it Related to Physiology or Inflammation?

Why some patients with achalasia lose weight and other patients do not is unknown due to paucity of focus in this area. One of the first studies evaluating clinical response in achalasia with pneumatic dilatations noted weight loss in approximately 91% of patients (n= 264) with 16 patients reporting > 20kg and 18 patients reporting < 5kg of weight loss.26 However, this might have been skewed given most patients in this study noted duration of symptoms ranging from 2 to >20 years prior to diagnosis and treatment with pneumatic dilatation. This “diagnosis latency” of achalasia is very common; many patients have had symptoms for years before seeking medical treatment. Subsequently, 3 to 13 years after treatment, these patients rapidly gained weight and weight loss was only observed in <6% of patients.26 Thus, post-therapy patients that have lost weight are able to gain it back.

What is interesting about achalasia is that despite the mechanical obstruction in all, many do not lose weight, and in fact, some are obese. One small surgical series reported 3 patients with achalasia and morbid obesity (BMI of 43.3, 60, and 52.7), who did not have typical symptomatic presentation with dysphagia, but all 3 reported significant respiratory symptoms with nocturnal cough and recurrent aspiration.27 The question of sub-types of achalasia and weight loss may be of physiologic interest. In a retrospective study assessing clinical, radiological, and manometric profiles of 145 patients with untreated achalasia, the authors reported that 31% of patients with classic achalasia reported weight loss compared to 43% of patients with vigorous achalasia.8 Although the degree of weight loss was not significantly different between the two at 20 ± 16 lbs, patients with vigorous achalasia had a significantly higher percent with normal LES pressure (49% vs. 13%).8 Thus, it is not clear if LES physiology is related to presence or absence of weight loss, as one would expect patients with higher LES pressure to report more weight loss.

Another prospective study evaluating 213 achalasia patients (110 men and 103 women) investigated differences in clinical presentation based on gender. They noted that mean duration of symptoms, age at diagnosis, and mean weight loss (3.2 kg) were not significantly different between men and women; however, they did not differentiate between the sub- types of achalasia.28

Interestingly, a recent cross-sectional study evaluating 623 patients with dysphagia in Iran tried to explore the sensitivity, specificity, and predictive accuracy of presenting esophageal symptoms to normal or abnormal esophageal motility testing.29 They noted that no clinical symptoms were sensitive enough to discriminate between normal and abnormal esophageal motility testing, but did find that presence of dysphagia, non-cardiac chest pain, hoarseness, vomiting, and weight loss had high specificity and high accuracy in distinguishing esophageal motor disorders from normal findings. Eighty-five out of 623 (14%) had achalasia; the type II achalasia group reported more frequent weight loss (26%), followed by Type I (11%), then Type III (1%).29 Why patients with type II would be at higher risk of losing weight remains a mystery.

Furthermore, if weight loss is not predicted by physiology, it may be related to an inflammatory process by an increase in cytokines (such as in patients with IBD). A recent study evaluated histopathologic patterns among achalasia subtypes and noted that type I achalasia specimens had significantly more myenteric plexus ganglion cell loss compared to type II, suggesting that type I achalasia likely represented disease progression from type II.30 Whether a higher degree of histopathologic inflammation in type II achalasia patients might explain the weight loss in this group compared to type I needs further study. In addition, it is also possible that certain patients eat significantly less and make calorie-poor choices compared to other patients; unfortunately, these patients are rarely referred to dietitians for appropriate nutritional education until after achalasia is treated.

NUTRTIONAL IMPLICATIONS

Nutrition in patients with achalasia has often been overlooked. In fact, there are currently no published studies or reviews in this area. The advice that is often given is “eat what you can tolerate.” This is likely due to high treatment success in achalasia, which often allows the patient to resume their regular diet without significant alterations almost immediately. However, dietary modifications should be highly considered as adjunctive treatment in patients that undergo other less effective treatment modalities such as Botox injections or pharmacologic treatment with medications as it could potentially assist with maintaining adequate nutrition. We prospectively evaluated the nutritional status of 19 patients with untreated achalasia with 80% reporting having altered their diet due to swallowing difficulties; 90% reported consuming less than usual. In addition, 80% of patients reported an estimated weight loss of 40 pounds over the course of approximately 6 months.31 Studies are now underway to assess the magnitude and mechanism of nutritional deficiencies in achalasia as well as prospectively assess response to therapy.

Physiologically, a low fiber diet (defined as maximum of 10g fiber/day) could be considered in these patients similar to patients who have small bowel stricture. Soluble fiber increases the viscosity of the bolus, which reduces absorption and insoluble fiber possess high water-binding capacity and increases the bulk of the bolus. However, in the setting of luminal narrowing, as in achalasia due to high LES pressure, a low fiber diet would be physiologically advantageous to allow easier passage through a small narrowing. Fiber bulking agents should also be avoided until treated. Some patients may need to switch to high calorie/ protein liquids also. It is also prudent to consider prompt referral to a registered dietitian in patients who are having difficulty regaining weight. In those with significant weight loss, refeeding will need to be done cautiously to prevent refeeding syndrome. Thiamine supplementation (as well as other vitamins and minerals) might also be needed in patients with persistent vomiting.

Eating frequent, small, low-fiber meals with higher liquid content should be encouraged until they are able to get definitive treatment for achalasia. In those who continue to have trouble meeting their nutrient requirements orally, gastric access for enteral feeding may be necessary, but rarely needed due to effective therapeutic options available for achalasia. However, given the paucity of data regarding nutrition in achalasia patients, we strongly recommend future focus in this very important clinical area.

CONCLUSION

Achalasia is one of the most studied motility disorders of the esophagus and is characterized by impaired LES relaxation. Patients often present with dysphagia, significant regurgitation, and some have a tremendous degree of weight loss. Despite significant resources allocated to understanding the physiology and treatment options in patients with achalasia, it is still unclear why certain patients with achalasia lose significantly more weight compared to others. Although achalasia cannot be permanently cured, excellent palliation of symptoms is possible in > 90% of patients with currently available treatment modalities. In patients that are not candidates for more definitive therapies such as pneumatic dilatation, Heller myotomy, or POEM, we advocate combination of botulinum toxin injection and focus on dietary alterations with eating small, frequent, low- fiber meals with higher liquid content to help maintain nutritional needs.

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