Brian P. Riff

Sendai and Fukuoka Consensus Guidelines Identify Advanced Neoplasia in Patients With Suspected Mucinous Cystic Neoplasms of the Pancreas

BACKGROUND & AIMS Little is known about whether the 2006 Sendai guidelines or 2012 Fukuoka guidelines are being used to determine the level of risk posed by suspected pancreatic mucinous cystic neoplasms (PCNs). We evaluated whether the guidelines accurately predicted which patients with suspected PCNs, which was based on cross-sectional imaging findings, would be found to have advanced neoplasia in surgery. METHODS We performed a retrospective study of data collected from 194 patients with cystic lesions of the pancreas, which were assessed by cross-sectional imaging analyses, who underwent surgery for suspected PCNs at the Hospital at the University of Pennsylvania from 2000 through 2008. Imaging data were used to classify patients according to the Sendai guidelines as high risk or low risk and according to the Fukuoka guidelines as high risk, worrisome, or low risk. Pathology analyses of samples collected during surgery were used as the reference. A logistic regression model was created to identify factors associated with advanced neoplasia. The Sendai and Fukuoka guideline criteria were analyzed by univariate and multivariable logistic regression analyses. RESULTS Advanced neoplasias were found in 36 patients (18.5%; 22 invasive cancers and 14 high-grade dysplasias). The median size of cysts was 33 mm. All patients found to have invasive cancers were accurately assigned to the Sendai guidelines high risk or Fukuoka guidelines high risk groups. However, 3 patients in the Sendai guidelines low risk and 2 patients in the Fukuoka guidelines low risk groups were found to have high-grade dysplasia. The Sendai guidelines identified patients with advanced neoplasia with 91.7% sensitivity, 21.5% specificity, 21% positive predictive value, and 91.9% negative predictive value. A designation of Fukuoka guidelines high risk identified patients with advanced neoplasia with 55.6% sensitivity, 73% specificity, 32% positive predictive value, and 87.9% negative predictive value. Overall, there was no statistically significant difference between the guidelines in predicting which patients had advanced neoplasia. On multivariate analysis, the presence of a mural nodule (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.33-6.27; P = .008), dilated main pancreatic duct >10 mm (OR, 7.44; 95% CI, 2.36-23.52; P = .001), or enhancing solid component (OR, 2.92; 95% CI, 1.16-7.64; P = .02) were associated with detection of advanced neoplasia in pancreatic cysts. CONCLUSION On the basis of a retrospective analysis, the Sendai and Fukuoka guidelines accurately determine which patients with pancreatic cysts have advanced neoplasia. The guidelines accurately recommended surgical resection for all patients found to have invasive cancer, although some patients with high-grade dysplasia were missed. The updated Fukuoka guidelines are not superior to the Sendai guidelines in identifying neoplasias. Cyst size was not associated with advanced neoplasia.

Peptide Receptor Radionuclide Therapy-Induced Hepatotoxicity in Patients With Metastatic Neuroendocrine Tumors.

Background Treatment of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with peptide receptor radionuclide therapy (PRRT) is effective in retarding tumor growth. Renal dysfunction, anemia, and thrombocytopenia are well-described treatment-related toxicities. However, hepatotoxicity is not well recognized. Patients and Methods We performed a retrospective cohort study of consecutive patients with GEP-NETs seen in a tertiary NET clinic from January 2010 to September 2013 (n = 211) with the primary study cohort being patients with metastatic disease to the liver (n = 93). The study exposure was PRRT, and the primary outcome of interest was hepatotoxicity. Hepatotoxicity was defined as a grade 2 or greater injury according to the Common Terminology Criteria for Adverse Events version 3.0 of the National Cancer Institute. Results Seventeen (18%) of 93 patients with liver metastases received PRRT after radiographic confirmation of disease progression despite receipt of other traditional therapies. Peptide receptor radionuclide therapy patients were similar to the unexposed patient population in terms of sex, age, baseline laboratory values, prior treatment exposure, and duration of disease. In the unexposed group, 23 (30%) of 76 patients had hepatotoxicity related to traditional GEP-NET therapy. In the exposed group, 10 (59%) of 17 patients had an episode of hepatotoxicity. Ascites developed in 59% of the PRRT group versus 6.6% in the unexposed group (P < 0.001). The calculated relative risk of hepatotoxicity related to PRRT exposure in metastatic GEP-NET patients was 1.94 (95% confidence interval, 1.15–3.28). Conclusions Hepatotoxicity after PRRT for metastatic GEP-NET is more common than previously reported.

Efficacy of Peptide Receptor Radionuclide Therapy in a United States–Based Cohort of Metastatic Neuroendocrine Tumor Patients: Single-Institution Retrospective Analysis

Objectives The aim of this study was to analyze in a retrospective cohort study the outcomes of a United States–based group of metastatic neuroendocrine tumor (NET) patients who underwent peptide receptor radionuclide therapy (PRRT). Methods Twenty-eight patients from a single US NET Center were treated with PRRT. Toxicities were assessed using Common Terminology Criteria for Adverse Events version 4.03. Progression was determined by the Response Evaluation Criteria in Solid Tumors version 1.1. Univariate and multivariate Cox regression was performed to identify potential predictors of progression-free survival (PFS) and overall survival (OS). Results The median age at NET diagnosis was 56 years, 50% of the patients were male, 46% of NET primaries were located in the pancreas, 71% of tumors were nonfunctional, 25% were World Health Organization (WHO) grade III, and 20% had at least a 25% hepatic tumor burden. Anemia (36%) was the most common post-PRRT toxicity, followed by leukopenia (31%), nephrotoxicity (27%), and thrombocytopenia (24%). Median PFS was 18 months, and median OS was 38 months. Having a WHO grade III NET and receiving systemic chemotherapy prior to PRRT were found to be to independent predictors of shorter PFS and OS. Conclusions Peptide receptor radionuclide therapy is an effective therapy in a US population. Progression-free survival and OS were better in WHO grade I/II NETs and when PRRT was sequenced prior to systemic chemotherapy.

Glasgow Blatchford Score of limited benefit for low-risk urban patients: a mixed methods study

Background and study aims  Most patients with upper gastrointestinal bleeding (UGIB) are hospitalized. Risk-stratifying UGIB with scoring tools may decrease avoidable admissions, thereby reducing the cost of care. We sought to describe how frequently low-risk UGIB patients present to urban emergency departments (ED) and the proportion who are admitted to examine how incorporating risk scores into decision support might diminish healthcare utilization in this population. Patients and methods  This is a retrospective cohort study of ED patients presenting from 2009 – 2013 to three urban hospitals that do not use electronic UGIB decision support. We used ED disposition diagnosis codes (ICD-9) to identify patients followed by manual chart review for verification and additional data collection. Patients with a Glasgow Blatchford Score (GBS) of 0 were classified as low risk. We also surveyed ED physicians at these hospitals to assess their beliefs about UGIB decision support. Results  Over the study period, 66 patients (13.2 per year) presented to the ED with low-risk UGIB. Of these, 10 patients (15.2 %) were admitted and none required endoscopic hemostasis. Most survey respondents (55.6 %, n = 20) were aware of UGIB risk scores but a minority (19.4 %, n = 7) used one. Conclusions  Low-risk UGIB patients infrequently present to the ED and only a minority are admitted. Despite advocacy to incorporate decision support into routine clinical care, ED physicians independently identified low risk patients. There is insufficient evidence to suggest the magnitude of this problem is large enough to warrant implementation of decision support for low risk UGIB.

Weight Gain in Zollinger-Ellison Syndrome After Acid Suppression:

Objectives Zollinger-Ellison syndrome (ZES) is characterized by hypergastrinemia and gastric acid hypersecretion resulting in peptic ulcer disease, diarrhea, and weight loss. Acid secretion can be controlled with medication, and biochemical cure is possible with surgery. Data on how these interventions affect patients’ weight are lacking. We aimed to determine how medical and surgical acid control affects weight over time. Methods We performed a retrospective cohort study on 60 ZES patients. Acid control was achieved with appropriate-dose proton pump inhibitor (PPI) therapy. Surgery was performed for curative intent when appropriate. Weight change was assessed versus pre–acid control or immediate preoperative weights and expressed as absolute and percent change from baseline at 6, 12, 18, and 24 months. Results A total of 30 PPI-controlled patients and 20 surgery-controlled patients were analyzed. Weight gain was noted at all time points while on appropriate-dose PPI therapy (P < 0.005). Of patients who had surgery with curative intent, weight gain was noted at 12 months (7.9%, P = 0.013) and 18 months (7.1%, P = 0.007). There was a trend toward weight gain seen at all time points in the patients who were surgically cured. Conclusions These data represent a novel description of weight gain after acid suppression in ZES.

HNPCC-associated pheochromocytoma: expanding the tumor spectrum.

characteristic of type 1 AIP and IgG4RD. In this case, we observed a MCN accompanied by all 3 of these features.Moreover, the number of IgG4+ plasma cells over 50/hpf and the IgG4+/IgG+ ratio greater than 40% fulfilled the Boston criteria for AIP/ IgG4-RD. The pancreatic tissue away from the cyst was completely normal, and further clinical and radiologic work-up did not reveal extrapancreatic manifestations of IgG4-RD. Furthermore, the clinical symptoms resolved after resection of the tumor. Therefore, we consider that the dense lymphoplasmacytic infiltrate with features of IgG4-RD surrounding the MCN in this case is not indicative of AIP/IgG4-RD, and likely represents an inflammatory antitumor response driven by Th2 cytokines. There is accumulating evidence that increased IgG4+ plasma cells may be associated not only with classic IgG4-RD but also with a variety of non-neoplastic and neoplastic conditions. The IgG4+ plasma cells may be significantly increased in inflammatory processes, including rheumatoid synovitis, oral cavity lesions including epulis plasmacellularis, radicular cysts, and oral lichen ruber. Elevated numbers of IgG4 have also been described as a component of antitumor inflammatory response in several malignancies from different sites, including pancreatic ductal adenocarcinoma and IPMN 4–8 (Table 1). It is not clear whether the morphologic features characteristic of AIP/IgG4-RD occur synchronously or precede IPMNs, or longstanding IPMNs induce IgG4+ plasma cell response. Although some authors proposed that IPMN may develop in a background of AIP based on the presence of lymphoplasmacytic infiltration with abundant plasma cells and storiform fibrosis at a location distant from IPMN, other hypothesized that the histologic changes consistent with type 1 AIP may be a secondary phenomenon that appeared several years after IPMN. The characteristic feature common to both pancreatic MCN and IPMN is mucin production. We have recently described that the sclerosing variant of mucoepidermoid carcinoma of salivary glands is associated with increased IgG4+ plasma cells. All 6 cases of sclerosing mucoepidermoid carcinoma demonstrated small areas of mucin extravasation composing 5% to 10% of the tumor mass. Although no definitive mucus extravasation was identified in this case, we hypothesize thatmucin extravasation in these tumors may elicit an unusual immune response. In summary, we described the first case of pancreaticMCN associatedwith histologic features of AIP/IgG4-RD. This appears to be a relatively rare phenomenon, but one which should be considered when evaluating

Vascular Injury Following Pyloric Dilation: Unusual Cause of Ischemic Colitis

A 57-year-old female with intrahepatic cholangiocarcinoma underwent hepatic trisegmentectomy and chemoradiation. Her course was complicated by recurrent episodes of radiation-induced gastric outlet obstruction requiring balloon dilations. She presented with right lower quadrant pain after routine upper endoscopy with pyloric dilation. A computed tomography (CT) showed isolated right-sided ischemic colitis with vascular contrast in the mesentery. Repeat CT after conservative management revealed near resolution of the ischemic changes. Perforation at the level of the pylorus is a complication of endoscopic pyloric dilation but vascular injury has never been described.