J.-Y. Jang

Cyst Growth Rate Predicts Malignancy in Patients With Branch Duct Intraductal Papillary Mucinous Neoplasms

BACKGROUND & AIMSnLittle information is available about the clinico-pathologic characteristics of pancreatic branch duct intraductal papillary mucinous neoplasm (Br-intraductal papillary mucinous neoplasm [IPMN]) because of difficulties in diagnosis based on radiologic and tissue information. We investigated the natural history of Br-IPMN using imaging and surgical pathology data from patients.nnnMETHODSnData were collected from patients admitted to a single tertiary referral institution from January 2000 to March 2009 (median follow up of 27.9 months); 201 patients were diagnosed with Br-IPMN with an initial cyst less than 30 mm without main pancreatic duct dilatation or mural nodules. The patients were followed for more than 3 months and examined by computed tomography (CT) at least twice.nnnRESULTSnThe mean size of the patients initial cysts was 14.7 mm; the mean cyst growth rate was 1.1 mm/year. Thirty-five patients received surgery during follow up and 8 were confirmed to have malignant cysts. The malignant cysts were greater in final size than nonmalignant cysts (24.3 mm vs 16.9 mm; P = .003); they also grew by a greater percentage (69.8% vs 19.4%; P = .046) and at a greater rate (4.1 mm vs 1.0 mm/year; P = .001). The actuarial 5-year risk of malignancy was 41.6% in the group that received surgery and 10.9% for all patients. Cysts that grew more than 2 mm/year had a higher risk of malignancy (5-year risk = 45.5% vs 1.8%; P < .001).nnnCONCLUSIONSnIn combination with cyst size and the presence of mural nodules, cyst growth rate could be used to predict malignancy in patients with Br-IPMN.

Validation of international consensus guidelines for the resection of branch duct‐type intraductal papillary mucinous neoplasms

Classifications of intraductal papillary mucinous neoplasm (IPMN) remain ambiguous, especially for the mixed type. Factors predicting malignancy remain unclear. The aim of this study was to evaluate the usefulness of factors predicting malignancy in the new international consensus guidelines for resection of branch duct‐type (BD)‐IPMN and to compare them with those in the previous version.

Effects of pancreatectomy on nutritional state, pancreatic function and quality of life

There are concerns about the extent of impaired endocrine and exocrine pancreatic function and poor quality of life (QoL) after pancreatectomy, but there is little information from large prospective follow‐up studies.

Bile-Based Detection of Extrahepatic Cholangiocarcinoma with Quantitative DNA Methylation Markers and Its High Sensitivity

Extrahepatic cholangiocarcinoma (EHC) is usually difficult to diagnose by bile cytology because of cellular disintegration. However, DNA samples from bile fluid can provide sufficient materials to screen for the presence of EHC. We developed DNA methylation marker panels that can be used for MethyLight assay-based detection of EHC in bile fluid specimens. The methylation status of 59 DNA methylation markers was investigated in 20 EHC and 20 non-neoplastic gallbladder tissue samples with MethyLight assay to determine cancer-specific DNA methylation markers. Through assaying cancer-specific DNA methylation markers in a training set (n = 40) and validation set (n = 45) of bile fluid specimens from patients with EHC or those without cancer, we selected suitable marker panels that were assessed for their performance in a third set (test set; n = 40). Four marker panels showed a sensitivity of 60% or more and a specificity of 100% in both the training and validation sets, whereas bile cytology displayed a sensitivity of 40% to 46% and a specificity of 100%. In an independent test set of bile fluid samples, a five-gene panel (CCND2, CDH13, GRIN2B, RUNX3, and TWIST1) detected EHC at a sensitivity of 83%, which was far higher than that of bile cytology (46%, P = 0.004). Using bile fluids, a methylation assay consisting of a five-gene panel may be useful for detecting EHC and in helping to increase the sensitivity of preoperative diagnoses.

Changing trend in bile microbiology and antibiotic susceptibilities: over 12 years of experience

PurposeRapidly changing medical environments may have changed the microbiology of infected bile. The aim of our study was to identify the changing trends in microorganisms in biliary infections and examine their susceptibilities against currently recommended antibiotics.MethodsBile cultures taken between 1998 and 2010 at Seoul National University Hospital, a tertiary medical center, were retrospectively reviewed. From 1,403 patients, 3,425 microorganisms were isolated from 2,217 cultures. The cultures were then tested to determine the types of microorganisms and their antibiotic susceptibility.ResultsThe five most frequently isolated microorganisms were Enterococcus (22.7xa0%) followed by Escherichia (13.2 %), Pseudomonas (10.9 %), Klebsiella (10.3 %), and Enterobacter (7.2xa0%). The trend in annual incidence indicated a growing emergence of Enterococcus (Pxa0<xa00.001). Among Enterococcus, E. faecium acquired a dominant position (50.6xa0%), showing an increasing trend over the study period (Pxa0=xa00.026). The incidence of vancomycin-resistant Enterococcus also showed an increasing trend (Pxa0<xa00.001). Many of the commonly used antibiotics provided inadequate coverage for the more frequently encountered microorganisms. Multiple regression revealed that benign causes of obstruction and non-operative treatment harbor an increased risk for enterococcal growth (Pxa0=xa00.001 and Pxa0=xa00.027, respectively).ConclusionsIn contrast to earlier reports, we found that Enterococcus has emerged as the most frequently isolated microorganism from bile. The importance of enterococcal infection should be recognized, and currently recommended antibiotics need to be re-evaluated since in our bile cultures most provided inadequate coverage for the more frequently encountered microorganisms. The changes in the trends of microorganisms isolated from bile should be considered in cases where patients present with biliary obstruction.

Long-Term Outcome of Cystic Lesions in the Pancreas: A Retrospective Cohort Study

Background/Aims The management guidelines for cystic lesions of the pancreas (CLPs) are not yet well established. This study was performed to document the long-term clinical outcome of CLPs and provide guidelines for the management and surveillance of CLPs. Methods In this retrospective cohort study, an additional follow-up was performed in 112 patients with CLPs enrolled from 1998 to 2004 during a previous study. Results During follow-up for the median period of 72.3 months, the size of the CLPs increased in 18 patients (16.1%). Six of these patients experienced growth of their CLPs after 5 years of follow-up. Twenty-six patients underwent surgery during follow-up, and four malignant cysts were detected. The overall rate of malignant progression during follow-up was 3.6%. The presence of mural nodules or solid components was independently associated with the presence of malignant CLPs. Seven patients underwent surgery after 5 years of follow-up. The pathologic findings revealed malignancies in two patients. There was only one pancreas-related death during follow-up. Conclusions The majority of CLPs exhibit indolent behavior and are associated with a favorable prognosis. However, long-term surveillance for more than 5 years should be performed because of the potential for growth and malignant transformation in CLPs.

Which method of pancreatic surgery do medical consumers prefer among open, laparoscopic, or robotic surgery? A survey

Purpose The consumers preferences are not considered in developing or implementing new medical technologies. Furthermore, little efforts are made to investigate their demands. Therefore, their preferred surgical method and the factors affecting that preference were investigated in pancreatic surgery. Methods Six-hundred subjects including 100 medical personnel (MP) and 500 lay persons (LP) were surveyed. Questionnaire included basic information on different methods of distal pancreatectomy; open surgery (OS), laparoscopic surgery (LS), and robotic surgery (RS). Assuming they required the operation, participants were told to indicate their preferred method along with a reason and an acceptable cost for both benign and malignant conditions. Results For benign disease, the most preferred method was LS. Limiting the choice to LS and RS, LS was preferred for cost and well-established safety and efficacy. OS was favored in malignant disease for the concern for radicality. Limiting the choice to LS and RS, LS was favored for its better-established safety and efficacy. The majority thought that LS and RS were both overpriced. Comparing MP and LP responses, both groups preferred LS in benign and OS in malignant conditions. However, LP more than MP tended to prefer RS under both benign and malignant conditions. LP thought that LS was expensive whereas MP thought the cost reasonable. Both groups felt that RS was too expensive. Conclusion Though efforts for development of novel techniques and broadening indication should be encouraged, still more investments and research should focus on LS and OS to provide optimal management and satisfaction to the patients.

Role of resection for Bismuth type IV hilar cholangiocarcinoma and analysis of determining factors for curative resection

Purpose Extended liver resection may provide long-term survival in selected patients with Bismuth type IV hilar cholangiocarcinoma (HCCA). The purpose of this study was to identify anatomical factors that predict curative-intended resection. Methods Thirty-three of 159 patients with Bismuth type IV HCCA underwent major hepato-biliary resection with curative intent (CIR) between 2000 and 2010. Disease extent and anatomical variations were analyzed as factors enabling CIR. Results CIR ratio with hilar trifurcation bile duct variation (13/16) was significantly higher than that with other bile duct variation types (18/25). Hilum to left second bile duct confluence and tumor infiltration over left second bile duct confluence lengths in right-sided CIR were significantly shorter than those lengths in left-sided CIR (10.8 ± 4.9 and 2.7 ± 0.8 mm vs. 16.5 ± 8.4 and 7.0 ± 5.3 mm, respectively). Left-sided CIR patients had a marginally higher proportion of tumors invading ≤5 mm over the right second confluence than that in right-sided CIR patients (13/17 vs. 6/16; P = 0.061). The 3-year survival rate after CIR (28%) was significantly higher than after non-CIR (6.1%). Conclusion We recommend the criteria of CIR as bile duct variation type, length of hilum to contralateral second bile duct confluence, and extent of tumor infiltration over the second confluence for Bismuth type IV HCCA.

Proposed new staging system for ampulla of Vater cancer with greater discriminatory ability: multinational study from Eastern and Western centers

We built a multinational retrospective database of patients with ampulla of Vater cancer to develop a reliable new staging system.

Senp2 expression was induced by chronic glucose stimulation in INS1 cells, and it was required for the associated induction of Ccnd1 and Mafa

ABSTRACT Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in β cells. However, the role of SUMO modification in β cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in β cell mass. Treatment with 25 mM glucose for 72 h induced Senp2 mRNA expression but not that of Senp1 in INS1 cells. Immunohistochemical staining with anti-SENP2 antibody on human pancreas sections revealed that SENP2 was localized in the nucleus. Moreover, in a patient with type 2 diabetes, SENP2 levels were enhanced, especially in the cytoplasm. Senp2 cytoplasmic levels were also increased in islet cells in obese diabetic mice. Cell number peaked earlier in INS1 cells cultured in high-glucose conditions compared to those cultured in control media. This finding was associated with increased Ccnd1 mRNA expression in high-glucose conditions, and siRNA-mediated Senp2 suppression abrogated it. Mafa expression, unlike Pdx1, was also dependent on Senp2 expression during high-glucose conditions. In conclusion, Senp2 may play a role in β cell mass in response to chronic high-glucose through Cyclin D1 and Mafa.