John M. Levenick

Radiofrequency ablation for long- and ultralong-segment Barrett's esophagus: a comparative long-term follow-up study

BACKGROUND The safety, efficacy, and durability of radiofrequency ablation (RFA), with or without EMR, have been established for long-segment Barretts esophagus (LSBE). Ablating ultralong-segment Barretts esophagus (ULSBE) may be associated with increased stricture formation, eradication failure, and treatment session requirements. OBJECTIVES Our primary objective was to compare eradication and stricture rates between LSBE (≥3 to <8 cm) and ULSBE (≥8 cm). Our secondary objective was to evaluate treatment durability and session requirements. DESIGN Retrospective review of prospectively collected data. SETTING Tertiary care facility. PATIENTS A total of 72 patients (34 ULSBE, 38 LSBE; mean Barretts segment length of 10.8 and 4.7 cm) underwent RFA between August 2005 and September 2010. Mean follow-up was 45 and 34 months, respectively. MAIN OUTCOME MEASUREMENTS Eradication and complication rates for ULSBE and LSBE. RESULTS Eradication rates for dysplasia (90% vs 88%, P = 1.0) and intestinal metaplasia (IM) (77% vs 82%, P = .77) were similar. ULSBE patients required more overall (P < .01) and circumferential (P < .01) RFA; however, stricture rates were identical (14%). There was no dysplasia recurrence, and IM recurrence was similar (ULSBE, 23%; LSBE, 16%; P = .52). At 3 years, IM remained eradicated in 65% of ULSBE and 82% of LSBE, without maintenance RFA. On multivariate regression analysis, increasing Barretts length was associated with a reduced likelihood for eradicating IM (odds ratio 0.87; 95% CI, 0.75-1.00), but not dysplasia (odds ratio 1.13; 95% CI, 0.95-1.35). LIMITATIONS Single center. CONCLUSION ULSBE can be treated in its entirety at each session with efficacy and safety comparable to LSBE. ULSBE requires more effort to achieve IM eradication, and RFA is less durable in maintaining this eradication at 3-year follow-up.

Chronic constipation: new diagnostic and treatment approaches

Chronic constipation is a highly prevalent disorder that affects approximately 15% of the US population. Chronic constipation refers to patients who have had symptoms for more than 6 months. In clinical practice, chronic constipation is often used interchangeably with the term functional constipation. This is best defined using the Rome III criteria, which involves an evaluation of stool frequency in addition to symptoms of straining, feelings of incomplete evacuation, and the need to use manual maneuvers to assist with stool evacuation. Symptoms can be burdensome, leading to a reduction in patients’ quality of life. As a national healthcare issue, chronic constipation is also important because it imposes a significant economic impact on the healthcare system. A number of treatment options are currently available, both over-the-counter and by prescription, although not all patients respond to these therapies. This review will focus on new medical treatment options for the management of chronic constipation, and the safety and efficacy of these agents will be reviewed. In addition, the efficacy of new diagnostic tests to evaluate colonic motility and anorectal function are described.

Is alcohol required for effective pancreatic cyst ablation? The prospective randomized CHARM trial pilot study.

Background and study aims: In this study, we aim to determine the safety and feasibility of an alcohol-free approach to pancreatic cyst ablation using a chemotherapeutic ablation cocktail. Patients and methods: In this prospective, randomized, double-blinded pilot study, 10 patients with known mucinous type pancreatic cysts underwent endoscopic ultrasound (EUS)-guided fine needle aspiration and then lavage with either 80 % ethanol or normal saline. Both groups were then treated with a cocktail of paclitaxel and gemcitabine. Primary outcomes were reduction in cyst volume and rates of complications. Results: At 6 months, patients randomized to the alcohol arm had an 89 % average volume reduction, with a 91 % reduction noted in the alcohol-free arm. Complete ablation was achieved in 67 % of patients in the alcohol-free arm at both 6 and 12 months, whereas the alcohol group recorded complete ablation rates of 50 % and 75 % at 6 and 12 months, respectively. One patient in the alcohol arm developed acute pancreatitis (20 %) with no adverse events in the alcohol-free arm. Conclusions: This study revealed similar ablation rates between the alcohol ablation group and the alcohol-free arm and demonstrates the safety and feasibility of an alcohol-free ablation protocol. This pilot study suggests that alcohol may not be required for effective cyst ablation.

CASE OF A CLOSED CHOLEDOCHOCELE WITH BILIARY AND PANCREATIC DRAINAGE VIA THE ACCESSORY DUCT CAUSING ACUTE PANCREATITIS

Type III choledochal cysts, also called choledochoceles, are rare cystic dilatations of the terminal biliary tree. We report the case of a ‘closed choledochocele’, in which the bile and ventral pancreatic ducts emptied into the cyst, but because there was no outlet into the duodenum, drainage was retrograde via the accessory duct. This type of choledochocele variant has never previously been described in the medical literature.

Crystal-Associated Colitis with Ulceration Leading to Hematochezia and Abdominal Pain

Lower GI bleeding is a common cause for hospitalization in adults. Medication-associated mucosal injury is an important clinical entity that can result in significant morbidity and mortality. We present the case of a 45-year-old woman with a 3-month history of intermittent abdominal cramping and rectal bleeding. Her medical history was extensive and included end-stage renal disease and a remote history of endometrial carcinoma that was treated with radiation. Initial workup was concerning for ischemic and radiation colitis, however, histology was most consistent with acute inflammation and ulceration associated with crystal fragments. Sevelamer and cholestyramine are commonly used ion-exchange resins that have been associated with mucosal damage. Both medications were discontinued and her symptoms resolved. Our case highlights an underrecognized but important cause of hematochezia.

Percutaneous debridement and washout of walled-off abdominal abscess and necrosis using flexible endoscopy: a large single-center experience

Background and study aims: Direct percutaneous endoscopic necrosectomy has been described as a minimally invasive intervention for the debridement of walled-off pancreatic necrosis (WOPN). In this retrospective cohort study, we aimed to confirm these findings in a US referral center and evaluate the clinical value of this modality in the treatment of pancreatic necrosis as well as other types of intra-abdominal fluid collections and necrosis. Patients and methods: Twelve consecutive patients with WOPN or other abdominal abscess requiring debridement and washout underwent computed tomography (CT)-guided drainage catheter placement. Each patient then underwent direct percutaneous endoscopic necrosectomy and washout with repeat debridement performed until complete. Drains were then removed once output fell below 30 mL/day and imaging confirmed resolution. The primary endpoints were time to clinical resolution and sustained resolution at 1-year follow up.  Results: Ten patients were treated for WOPN, one for necrotic hepatic abscesses, and one for omental necrosis. The median time to intervention was 85 days with an average of 2.3 necrosectomies performed. Complete removal of drains was accomplished in 11 patients (92 %). The median time to resolution was 57 days. No serious adverse events occurred; however, one patient developed pancreaticocutaneous fistulas. Ten patients completed 1-year surveillance of which none required drain replacement. No patients required surgery or repeat endoscopy. Conclusions: This series supports the premise that direct percutaneous endoscopic necrosectomy is a safe and effective intervention for intra-abdominal fluid collections and necrosis in appropriately selected patients. Our study demonstrates a high clinical success rate with minimal adverse events. This modality offers several potential advantages over surgical and transgastric approaches including use of improved accessibility, an excellent safety profile, and requirement for only deep or moderate sedation.

A phase II trial of human secretin infusion for refractory type B pain in chronic pancreatitis.

Objective We aimed to determine if intravenous synthetic human secretin (sHS) improves refractory type B pain in patients with chronic pancreatitis (CP). Methods In a phase II dose escalation trial, patients with CP received sHS of varying doses (0.05–0.8 µg/kg) for 3 days. The primary outcomes were changes in the visual analogue pain score (VAS), short form (SF) - 36, and opiate use from baseline at 30 days after infusion. Results Twelve patients (mean age, 42 years, 6 men) were included. Mean pain scores (VAS) were 5.79, 4.80, 4.72, and 4.90, at baseline, day 4, day 10, and day 30, respectively (P = 0.25, 0.19, and 0.27 when compared with baseline, respectively). Daily opiate use (oral morphine equivalents) decreased throughout the study from a baseline value of 136 to 111 mg on day 4 (P = 0.52) and to 104 mg on day 30 (P = 0.34). In subgroup analysis, women had the most improvement (VAS baseline, 5.42 vs VAS day 30, 3.67; P = 0.07; baseline morphine equivalents, 107 mg vs. 84 mg; P = 0.21). Conclusions In patients, especially women, with refractory type B pain from CP, intravenous sHS administration demonstrated a trend toward improvement in self-reported pain and opiate use at 30 days after infusion, although statistical significance was not achieved (clinicaltrials.gov registration number NCT01265875).

Efficacy and safety of liquid nitrogen cryotherapy for treatment of Barrett’s esophagus

AIM To evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE, with and without dysplasia, or intramucosal adenocarcinoma (IMC). METHODS This was a retrospective, single-center study carried out in a tertiary care center including 45 patients with BE who was treatment-naïve or who had persistent intestinal metaplasia (IM), dysplasia, or IMC despite prior therapy. Barrett’s mucosa was resected via EMR when clinically appropriate, then patients underwent cryotherapy until eradication or until deemed to have failed treatment. Surveillance biopsies were taken at standard intervals. RESULTS From 2010 through 2014, 33 patients were studied regarding the efficacy of cryotherapy. Overall, 29 patients (88%) responded to cryotherapy, with 84% having complete regression of all dysplasia and cancer. Complete eradication of cancer and dysplasia was seen in 75% of subjects with IMC; the remaining two subjects did not respond to cryotherapy. Following cryotherapy, 15 patients with high-grade dysplasia (HGD) had 30% complete regression, 50% IM, and 7% low-grade dysplasia (LGD); one subject had persistent HGD. Complete eradication of dysplasia occurred in all 5 patients with LGD. In 5 patients with IM, complete regression occurred in 4, and IM persisted in one. In 136 cryotherapy sessions amongst 45 patients, adverse events included chest pain (1%), stricture (4%), and one gastrointestinal bleed in a patient on dual antiplatelet therapy who had previously undergone EMR. CONCLUSION Cryotherapy is an efficacious and safe treatment modality for Barrett’s esophagus with and without dysplasia or intramucosal adenocarcinoma.

Su1239 A Prospective Trial of Secretin Infusion for Refractory Type B Pain in Chronic Pancreatitis

Background & Aims: Chronic pancreatitis (CP) is characterized by chronic inflammation and progressive pancreatic fibrosis leading eventually to the loss of exocrine and endocrine pancreas functions. The loss-of-function mutations of serine protease inhibitor Kazal type 1 (SPINK1) gene are associated with various forms of human CP. We previously showed that deletion of Spink3, the mouse homologue of SPINK1, causes pancreatitis-like changes in the mouse. Spink3-/mice die within 2 weeks after birth, making it impossible to monitor long-term effects of Spink3 deficiency. The aim of this study was to rescue the Spink3-/phenotype by generating Spink3-/mice with knocked-in SPINK1, and to characterize timedependent changes in the pancreas in this geneticmodel. Methods:We placedCAG promoterSPINK1 minigene (CAG-SP1) into diaphanous homolog 2 (Diap2) locus, which is located on X chromosome, using the Cre-Lox technology. X-inactivation is a process whereby one of the two copies of the X chromosome present in female mammals is inactivated. By utilizing X-inactivation, we were able to create mice in which SPINK level was partially, but not completely, reduced compared with the wild type. The CAG-SP1 knock-in mice were crossed to Spink3+/mice, thus generating Spink3-/-; CAG-SP1 knock-in mice. Mice were followed up for up to 6 months. Time-dependent changes in pancreatic histology, autophagy, inflammatory infiltration, acinar cell death, stellate cell activation, fibrosis, as well as trypsinogen activation and serum amylase were measured. Results: Spink3-/-;YXCAG-SP1, as well as Spink3-/-;XCAG-SP1/CAG-SP1 mice in which CAG-SP1 was present on both X chromosomes, showed no abnormalities in pancreas or any other organ during the 6 months of observation, indicating that human Spink1 rescues Spink3 deficiency in mice. Spink3-/-; XCAG-SP1/wild mice in which CAG-SP1 is present on only one of the two X chromosomes, showed slight growth retardation but were healthy and fertile. Pancreas of Spink3-/-; XCAGSP1/wildmice at birth contained both normal and degenerated acinar cells, with accumulation of autophagic vacuoles. The Spink3-/-;XCAG-SP1/wild mice time-dependently developed pathologic features of CP, including loss of acinar cells, intralobular fibrosis with activated stellate cells, and neutrophilic infiltration. In the interlobular areas, fibrosis was not evident, but instead prominent lipomatosis was observed. Interlobular ducts were dilated and contained protein plugs, which resembled CP in human. Older mice displayed acinar-ductal metaplasia and prominent expression of proto-oncogenes Egfr, Her2, and Ras, but did not develop pancreatic intraepithelial neoplasia. Conclusions: The results re-inforce the role of SPINK1/Spink3 deficiency in the development of CP and indicate that CP conditions trigger factors promoting pancreatic cancer development.

Hereditary Pancreatic Cancer

Pancreatic cancer (PC) is the fourth most common cause of death from cancer among adults in the USA with an estimated 49,000 diagnoses and 38,000 deaths from pancreatic duct adenocarcinoma (PDAC) in 2013. Eighty-five to 90% of patients present with disease that is not resectable (i.e., locally advanced or metastatic disease) at the time of diagnosis with a 3.5-month median survival for non-resected patients. In average-risk people, the lifetime risk of developing PC is 1 in 67 (1.49%) which increases with age with the mean age at diagnosis of 71 years. Modifiable risk factors include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, and certain abdominal surgeries and infections. However, certain groups, such as hereditary pancreatitis and those with a family history of PC, have increased risk to develop PDAC, especially at an early age. With 5-year survival rates, significant advances in the understanding of PC etiology and tumor biology, early detection, screening, and treatment are necessary. Given that only early or precancerous stages have reasonable expectation of low morbidity and mortality, increased efforts are imperative to improve risk stratification and early identification, while PC is still resectable in early-stage disease or premalignant conditions. Screening for hereditary pancreatic cancer is based on consensus opinion and only guideline based. Timing of screening is controversial, but the International Cancer of the Pancreas Screening (CAPS) recommends for Peutz-Jeghers patients to have endoscopic ultrasound (EUS) with or without MRI/MRCP starting at age 50, while expert opinions recommend EUS and CA 19-9 every 2 years starting at age 25 with or without CT scan.