Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass.

BACKGROUND AND AIMS: The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases, yet standard ERCP is not possible because of surgically altered gastroduodenal anatomy. Laparoscopy-assisted ERCP (LA-ERCP) has been proposed as an option, but supporting data are derived from single-center small case series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. METHODS: This is a retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all the following were achieved: reaching the papilla, cannulating the desired duct, and providing endoscopic therapy as clinically indicated. RESULTS: A total of 579 patients (median age, 51; 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (interquartile range [IQR], 109-210), with a median ERCP time of 40 minutes (IQR, 28-56). Median hospital stay was 2 days (IQR, 1-3). Adverse events were 18% (laparoscopy related, 10%; ERCP related, 7%; both, 1%) with the clear majority (92%) classified as mild/moderate, whereas 8% were severe and 1 death occurred. CONCLUSIONS: Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. The ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher because of the added laparoscopy-related events.

Thirty-day outcomes underestimate endocrine and exocrine insufficiency after pancreatic resection.

BACKGROUND: Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy. METHODS: Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection. RESULTS: 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency. CONCLUSION: Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency.

Mass-Forming Gastric Heterotopia of the Rectum: A Series of 3 Cases from a Single Tertiary Health Center.

BACKGROUND Gastric heterotopia is a benign entity found throughout the gastrointestinal tract but is rarely identified in the rectum. Since 1939, only 94 cases have ever been identified, and it can present as a mass formation with symptomatology that mimics colorectal malignancy. In some instances, malignancy has been shown to arise within rectal gastric heterotopia. Here, we present 3 cases from the past 20-year period of rectal gastric heterotopia at a single tertiary institution. CASE REPORT A 25-year-old man (case 1), a 58-year-old woman (case 2), and a 33-year-old man (case 3) were found to have polypoid mass-like lesions greater than 1.0 cm within the rectum. Following biopsy, pathology showed gastric oxyntic mucosa flanked by colorectal mucosa, thus indicating gastric heterotopia. Presenting symptoms from all patients consisted of unspecified anal pain, hematochezia, or a combination of both. All patients were treated with endoscopic mucosal resection (EMR), which provided relief of symptoms and confirmed no evidence of invasive malignancy. CONCLUSIONS Rectal gastric heterotopia can mimic malignancy and in very rare instances can harbor high-grade dysplasia as well as invasive carcinoma. EMR seems to be a definitive treatment that offers relief to patient symptomatology and reassurance that any dysplasia is identified and removed.

Single-session EUS-guided gastroenterostomy and EUS-guided gallbladder drainage in a patient with concomitant gastric outlet obstruction and acalculous cholecystitis.

Video 1Video presentation of a single session EUS-guided cholecystoduodenostomy and gastrojejunostomy.

Use of a novel helical tack system for the management of challenging upper gastrointestinal defects.

BACKGROUND AND AIMS: Increasingly, gastroenterologists are being asked to assist in the closure of defects. Although there are several available tools that can be used for defect closure, there remains a need for devices that are easy to use, effective, and durable. The aim of this case series is to demonstrate the use of a novel helical tack system in the closure of upper GI defects. METHODS: Two cases of challenging upper GI defects were identified. One case involved a perforated duodenal ulcer, and the other involved a nonhealing marginal ulcer. In both cases, the helical tack system was used for defect closure. RESULTS: In both cases, defect closure was achieved using the helical tack system; however, 2 series of tacks were required in each case. There were no adverse events. Neither patient has required additional surgical or endoscopic interventions. CONCLUSIONS: The helical tack system is a new device that may be useful for the closure of challenging upper GI defects. Additional comparative studies are needed to better understand the advantages and disadvantages of this system relative to other closure tools.

Endoscopic Management as a Viable Therapy for Pancreaticopleural and Pancreaticopericardial Fistulas.

Pancreatic fistulas are rare complications of chronic pancreatitis, typically caused when disruption of the pancreatic duct causes leakage of pancreatic fluid that erodes through neighboring organs and structures. Pancreatic fistulas to the pericardium and pleural spaces are extremely rare, and cases of multiple fistulas tracking from the pancreas have not been reported before. Management of these fluid collections is challenging with no consensus described in the current literature. We report a case of a patient with concurrent pancreaticopericardial and pancreaticopleural fistulas who improved with endoscopic management.

Novel dilation technique and stent selection to reduce periprocedural adverse events in left hepaticogastrostomy.

Video 1Video demonstration of left hepaticogastrostomy with the assistance of an angioplasty balloon.

Endoscopic Management of Giant Walled-Off Pancreatic Necrosis With a High Risk of Bleeding.

Walled-off pancreatic necrosis (WOPN) is one of the late complications of acute pancreatitis. We present a 37-year-old man who developed a large WOPN 6 weeks after treatment of severe complicated pancreatitis. Imaging studies revealed a necrotic retroperitoneal fluid collection measuring 27 × 12 × 27 cm with large crossing blood vessels. Cystogastrostomy was performed using a lumen-apposing metal stent. He underwent multiple necrosectomies with significant improvement in the cyst size. Bleeding is a major complication of direct endoscopic necrosectomy; hence, specific imaging and a careful approach should be taken into consideration, especially in WOPN with a high risk of bleeding.

Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool.

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens. Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF) of commonly altered genes (BRAF, CDKN2A, CTNNB1, GNAS, RAS, PIK3CA, PTEN, SMAD4, TP53 and VHL) was evaluated for their ability to identify and grade mucinous PCL. Results: Cytology showed a diagnostic sensitivity of 43.5% for mucinous PCL due in part to the impact of non-diagnostic (28.8%) and negative (50.5%) specimens. Incorporating an algorithmic approach or molecular analysis markedly increased the accuracy of cytologic evaluation. Detection of mucinous PCL by molecular analysis was 93.3% based on the detection of KRAS and/or GNAS gene mutations (p = 0.0001). Additional genes provided a marginal improvement in sensitivity but were associated with cyst type (e.g. VHL) and grade (e.g. SMAD4). In the surgical cohort, molecular analysis and the proposed algorithm showed comparable sensitivity (88.9% vs. 100%). Conclusions: Incorporating somatic molecular analysis in the cytologic evaluation of EUS-FNA increases diagnostic accuracy for detection, classification and grading of PCL. This approach has the potential to improve patient management.

Presurgical short term treatment of uterine fibroids with different doses of cetrorelix acetate: a double-blind, placebo-controlled multicenter study.

OBJECTIVE: To assess the efficacy and safety of different dosing schedules of cetrorelix acetate as a short term treatment for 4 weeks prior to surgery in patients with uterine fibroids. STUDY DESIGN: Randomized, double-blind, placebo-controlled study. Patients were 109 premenopausal women, with at least one uterine fibroid, more than 4 cm in diameter. Groups 1-3 received placebo, 5 and 10 mg of cetrorelix on days 1, 8, 15 and 22, respectively group 4 received 10mg of cetrorelix on days 1 and 15. MRI scan was performed at screening and on day 29. The main outcome measure was the reduction of uterine volume on day 29 and response, defined as >30% size reduction. RESULTS: Mean (+/-S.D.) reduction of uterine volume on day 29 (MRI scan) was 5.1+/-32.1% with placebo, 15.6+/-20.2% with 4 x 5 mg, 15.4+/-34.6% with 4 x 10 mg and 0.6+/-30.6% with 2 x 10 mg cetrorelix. Significant response versus placebo (p<0.05) occurred in the 4 x 10 mg group (42.3% versus 11.1%) CONCLUSIONS: Best objective response after 4 weeks of treatment was achieved after therapy with 4 x 10 mg of cetrorelix acetate. Short term presurgical treatment with the LHRH-antagonist cetrorelix is a flexible treatment protocol without any major side effects.

Utility of liquid-based cytologic examination of distal esophageal brushings in the management of Barrett esophagus: a prospective study of 45 cases.

INTRODUCTION: The goal of Barrett esophagus surveillance is to identify high-grade dysplasia (HGD) for eradication. Surveillance programs currently rely on limited histologic sampling; however, the role of cytology in this setting is not well studied. MATERIALS AND METHODS: From December 1, 2011 to March 30, 2014, 45 patients underwent 4 circumferential brushings of the distal tubular esophagus followed by standard 4-quadrant biopsies. One ThinPrep slide and 1 Cellient cellblock (Hologic, Boxborough, Mass) were prepared. Six cytopathologists evaluated each for adequacy, intestinal metaplasia (IM) and dysplasia. Findings were classified using the traditional 5-tier system used for biopsies. A prospectively modified 3-tier cytologic classification was also tested: negative for HGD, indeterminate for HGD, and HGD. Sensitivity, specificity, and kappa values (interobserver agreement) for cytology were calculated. RESULTS: Ten of 45 patients had nondiagnostic cytologies; none of whom had dysplasia on biopsy. Cytology had good sensitivity (82%) and specificity (88%) for identifying IM compared with biopsy with moderate interobserver agreement (pairwise average of Fleiss and Krippendorf kappa value = 0.589, 79% agreement). One case had IM on cytology not detected on histology. Six of 45 patients had dysplasia on biopsy including 1 intramucosal adenocarcinoma, 1 indeterminate for dysplasia, 2 high-grade dysplasias, and 2 low-grade dysplasias. A non-negative adequate cytology sample had a sensitivity of 100% and a specificity of 88% and 94% for the 5-tier and the 3-tier classification, respectively. CONCLUSIONS: Cytology appears to have good sensitivity and specificity for diagnosis of HGD, and cytology may be poised to synergize with advances in other techniques for management of patients with Barrett esophagus. Improvements in brushing devices may help to decrease the nondiagnostic rate.

Improved implantation rate after chemical removal of the zona pellucida.

OBJECTIVE: To evaluate the implantation rate achieved after chemical removal of the zona pellucida from day 5 human in vitro-derived embryos. DESIGN: Prospective, randomized, controlled study. SETTING: A tertiary care infertility clinic. PATIENT(S): Two hundred fifty-seven patients undergoing IVF with transfer of morulas or blastocysts on day 5 after oocyte retrieval. All patients had had at least two previous implantation failures. INTERVENTION(S): Chemical removal of zona pellucida by using acidic Tyrode's solution vs. no removal (controls). MAIN OUTCOME MEASURES: Clinical pregnancy rate and implantation rate per transfer. RESULT(S): Embryos without zona pellucida implanted at nearly twice the rate of control embryos (15.7% vs. 27.5%). The pregnancy rate was also significantly higher in the zona pellucida-free group than the control group (31.0% vs. 46.1%). Removal of zona pellucida was most effective in embryos with delayed development, which reached the morula or early cavitating stage on day 5 of in vitro culture (implantation rate, 12.1% vs. 25.7%). CONCLUSION(S): Chemical removal of zona pellucida from day 5 in vitro cultured human embryos is an effective and safe method of significantly improving the implantation rate, especially of embryos with delayed development.

Expression of angiopoietic factors in normal and type-I diabetes human placenta: a pilot study.

OBJECTIVES: Morphological changes of blood vessel wall have been described in placenta from pregnancies complicated by diabetes mellitus type-I. STUDY DESIGN: We measured mRNA expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and 2 (Ang-1 and Ang-2), their receptors VEGFR-1, VEGFR-2, Tie-2, fibroblast growth factor 2 (FGF-2), and its receptor FGF-2R in placental tissue of diabetes type-I patients, in normal term placenta, and endometrium of non-pregnant women by real time reverse transcriptase PCR. RESULTS: The expression of Ang-2 and VEGFR-1 mRNAs was significantly higher in placenta (P

Decreased concentrations of retinol-binding protein 4 in sera of epithelial ovarian cancer patients: a potential biomarker identified by proteomics.

Ovarian cancer is the fifth leading cause of cancer death in women. Absence of a reliable biomarker precludes early diagnosis of the disease. To identify new proteins with potential diagnostic or prognostic value for the therapy of ovarian cancer we performed comparative proteomic analysis of sera from ovarian cancer patients and healthy women. We analyzed serum samples from 10 patients diagnosed with epithelial ovarian cancer and 10 age-matched healthy women. To decrease the extremely wide dynamic range of protein concentrations in serum we used combinatorial hexapeptide libraries. Serum samples were then subjected to proteomic 2-DE analysis. Three proteins with differential abundance were found and identified by mass spectrometry: α-1-antitrypsin, apolipoprotein A-IV and retinol-binding protein 4. Identification of α-1-antitrypsin and apolipoprotein A-IV confirms previous studies but the identification of significantly decreased levels of RBP4 in ovarian cancer patients represents a novel observation. We verified the decrease of RBP4 levels in ovarian cancer patient sera by two independent methods and determined absolute RBP4 concentrations in patients and healthy women. We excluded possible non-cancer factors that could be responsible for the observed RBP4 decrease. We propose a connection of RBP4 with epithelial ovarian cancer and advocate the potential of RBP4 as a candidate diagnostic or prognostic biomarker.

Significance of ultrasound vaginal cervicometry in predicting preterm delivery.

BACKGROUND: The objective of the study was to verify whether ultrasound vaginal cervicometry, performed in the 18th-20th week of gestation, can effectively predict preterm delivery. MATERIAL/METHODS: 279 singleton pregnancies were prospectively studied from the middle of gestation until delivery. In the 18th-20th week of gestation we performed ultrasound vaginal cervicometry, which we used to determine the length of the cervix, judge the shape of the internal os, and evaluate the cervicometry as normal or abnormal on the basis of these parameters. With the aid of one-dimensional and multi-dimensional analysis, we tested the dependence of completed weeks of gestation and preterm delivery on the results of ultrasound cervicometry. RESULTS: 247 women completed the study. Cervicometry was evaluated as abnormal in 53 women (21.46%). We proved a significant dependence of delivery prior to the 34th week of gestation on cervical length (p<0.01), abnormal shape of the internal os (p<0.0001; RR=10.35), and abnormal cervicometric result (p<0.0001; RR=29.28). Delivery prior to the 37th week was also significantly dependent on all observed parameters. Of the individual cervicometric parameters, cervical length had the most significant impact on the completed weeks of gestation. CONCLUSIONS: The implementation of ultrasound vaginal cervicometry in the prenatal screening program can lead to effective and early selection of women with a significantly increased risk of preterm delivery.

Role of therapy or monitoring in preventing progression to gastric cancer.

It is generally accepted that intestinal-type gastric adenocarcinoma arises through a multistep process originating with chronic gastritis, progressing through stages of atrophy, intestinal metaplasia, and dysplasia and finally invasive carcinoma. This sequential process, known as the "Correa cascade" is in many instances initiated by Helicobacter pylori infection and perpetuated by a number of environmental and host factors. Given that the development of carcinoma can be the end point of this sequential process, there is great interest in determining which if any of these steps may be reversible. Clinical studies have shown that the eradication of H. pylori can lead to resolution of chronic gastritis, and a few studies have suggested some improvement in gastric atrophy. Intestinal metaplasia, however, does not appear to be as reversible. Nevertheless, results of several intriguing studies of high-risk populations support the notion that eradication of H. pylori may decrease or delay progression to gastric carcinoma despite the inability to reverse all mucosal damage. The applicability of these findings to low-risk countries such as the United States and the United Kingdom remain uncertain. Currently, in the United States, there is no widely accepted screening program for H. pylori infection in asymptomatic individuals, and consensus regarding surveillance for gastric intestinal metaplasia or dysplasia is lacking. The purpose of this report is to evaluate the available data regarding the epidemiology of H. pylori and associated carcinoma, discuss relevant human and animal data that address eradication strategies in the prevention of gastric carcinoma, and finally discuss current recommendations regarding screening programs aimed at high-risk populations.