Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Association between dietary calcium intake and the risk of cardiovascular disease among Korean adults.

BACKGROUND/OBJECTIVES: Although dietary calcium intake is associated with a risk of cardiovascular disease (CVD), it has not been studied extensively in Asian populations. We therefore investigated the association between dietary calcium intake and CVD among Korean adults and the effect of obesity on this association. SUBJECTS/METHODS: In total, 9186 participants were included in the analysis after excluding 844 with prevalent CVD/cancer or implausible energy intake. Nutrient intake, including dietary calcium, was estimated using a validated semi-quantitative food frequency questionnaire. CVD included myocardial infarction, coronary artery disease, and stroke per the World Health Organization criteria. Cox proportional hazards models were used to calculate multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: In the fully adjusted model, HRs of CVD across increasing quintiles of dietary calcium intake were 1.0 (reference), 0.85 (95% CI: 0.66-1.10), 0.77 (95% CI: 0.58-1.02), 0.59 (95% CI: 0.42-0.83), and 0.72 (95% CI: 0.48-1.08); a significant linear trend was detected (p for trend = 0.04). However, this association varied according to the obesity status. High dietary calcium intake was associated with a reduced CVD risk among nonobese participants (body mass index [BMI] < 25 kg/m2; p for trend = 0.02), whereas this was not significant among obese participants (BMI ≥ 25 kg/m2; p for trend = 0.88). CONCLUSIONS: The association between dietary calcium intake and incident CVD may be influenced by obesity status. We provide evidence for developing dietary calcium intake guidelines for Koreans, allowing for the effects of obesity.

Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.

VDJ Gene Usage of B Cell Receptors in Peripheral Blood of ABO-incompatible Kidney Transplantation Patients.

INTRODUCTION: B cell subtypes and immunoglobulin variable (V), diversity (D), joining (J) gene segment usage of B cell receptors in ABO-incompatible (ABOi) kidney transplantation (KT) in comparison to ABO-compatible KT have not been studied. The aims of this study were to analyze the VDJ gene segment usages of B cell receptors in peripheral blood of ABOi KT recipients. METHODS: Eighteen ABOi KT patients with accommodation (ABOiA), 10 ABO-compatible stable KT patients (ABOcS), and 10 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10 after transplantation were selected. Complete transcriptomes of their peripheral blood samples were sequenced and analyzed through RNA sequencing. RESULTS: By family, immunoglobulin heavy chain variable 3 (IGHV3), immunoglobulin light kappa chain variable 1 (IGKV1), immunoglobulin light lambda chain variable 2 (IGLV2), and immunoglobulin light lambda chain joining 3 (IGLJ3) gene segments were most frequently used in all groups, and their usage was not statistically different among the three groups except for IGHV3 and IGKV1. IGKV1 was more frequently used in the ABOiA group than in the ABOcS group. According to individual gene segments, IGHV3-7, IGHV3-15, IGHV4-59, IGKV3-11, IGLV1-44, IGLV2-14, IGLV4-69, and IGLV7-46 were more frequently used in the ABOcS group than other groups, and IGKV3-7 was more frequently used in the ABOiR group than other groups. IGLV5-52 and IGLV7-43 were more frequently used in the ABOiA group than in ABOcS group. CONCLUSIONS: Our findings suggest that RNA sequencing transcriptomic analyses of peripheral blood can provide information on the VDJ gene usage of B cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.

Prognostic relevance of lymph node status for patients with ampullary adenocarcinoma after radical resection followed by adjuvant treatment.

PURPOSE: Attempts have been made to revise the nodal stage due to simplicity of current N staging system in ampullary adenocarcinoma. However, because of the disease rarity, there have only been a few studies assessing the prognostic impact of lymph node (LN) parameters. METHODS: We retrospectively analyzed 120 patients who underwent radical resection followed by adjuvant chemoradiotherapy for ampullary adenocarcinoma. The effect of LN parameters (number of total harvest LNs, number of metastatic LN (MLN), lymph node ratio (LNR), and log odds of positive LNs (LODDS)) on overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival were evaluated. Cutoff points of MLN, LNR and LODDs were determined using maximal χ2 method. RESULTS: Fifty-seven patients (48%) were staged as pN1 and their survival was not significantly decreased compared with pN0 patients. There was also no significant difference between patients with MLN 0 vs. 1. In univariate analyses, MLN (0-1 vs. ≥2), LNR (≤17% vs. >17%) and perineural invasion were common prognosticators for OS and LRFS. Distant metastasis-free survival was not influenced by LN status. In addition, multivariate analysis revealed that among the LN parameters, LNR was able to independently predict both OS and LRFS. CONCLUSIONS: LNR performs better than other LN related parameters for predicting survival. After radical resection followed by adjuvant treatment, survival of patients with one positive LN does not seem to differ from patients without LN metastasis.

Serum 25-hydroxyvitamin D cutoffs for functional bone measures in postmenopausal osteoporosis.

This study sought to determine the minimal serum 25-hydroxyvitamin D [25(OH)D] concentration required to maintain bone health in postmenopausal women with low bone mass. A serum 25(OH)D concentration of 20 ng/mL rather than 30 ng/mL was appropriate for bone health. INTRODUCTION: There is no consensus on the minimal serum 25-hydroxyvitamin D [25(OH)D] concentration required to maintain bone health. The aim of this study was to investigate the relationship between 25(OH)D measured via liquid chromatography-mass spectrometry (LC-MS/MS), which is the current gold standard, and biochemical markers of bone turnover, PTH, and bone mineral densitometry (BMD). METHODS: The medical records of 750 postmenopausal women newly diagnosed with osteoporosis or osteopenia at Samsung Medical Center from 2009 to 2014 were investigated. Subjects were divided into four groups according to serum 25(OH)D concentration: <10, 10-20, 20-30, and ≥30 ng/mL. Serum concentrations of bone-specific alkaline phosphatase (BS-ALP), carboxy-terminal cross-linking telopeptide of type 1 collagen (CTx), intact PTH (iPTH), and BMD were compared among the four groups using analysis of covariance. Thresholds of 25(OH)D were then assessed using spline plots and locally weighted regression smoothing (LOESS) plots. RESULTS: 25(OH)D was negatively correlated with serum BS-ALP, CTx, and iPTH. Only femur neck and total femur BMD had significant positive relationships with 25(OH)D. Cutoff values of 11.9 and 9.7 ng/mL were estimated from the spline plots of femur neck and total femur BMD, respectively. For iPTH, the LOESS plot showed a steep decrease to a serum 25(OH)D concentration of about 20 ng/mL, followed by a plateau. CONCLUSIONS: According to this study, a serum 25(OH)D concentration of 20 ng/mL, rather than 30 ng/mL, was appropriate for bone health.

Immunologic characteristics of human gingival fibroblasts in response to oral bacteria.

BACKGROUND AND OBJECTIVE: There is ample evidence that gingival fibroblasts (GFs) participate in the immune response to oral bacteria and serve as immune-regulatory cells. The objective of this study was to investigate the innate immune response of GFs to oral bacteria. MATERIAL AND METHODS: Human GFs were cocultured with relatively less-pathogenic (Leptotrichia wadei, Fusobacterium nucleatum and Campylobacter gracilis) and pathogenic red-complex bacteria. The expression of mRNA for antimicrobial peptides [AMPs; namely human beta defensins (HBDs)], chemokines with antimicrobial activity [chemokine C-X-C motif (CXCL)10, CXCL11 and chemokine C-C motif ligand 20 (CCL20)] and proinflammatory mediators [interleukin (IL)6 and IL8] and the levels of CXCL11, CCL20, IL-6 and IL-8 accumulated in supernatants were analyzed using real-time PCR and ELISA, respectively. The proteolytic activities of CXCL11, CCL20, IL-6 and IL-8 produced by six species of bacteria were also determined. RESULTS: The relatively less-pathogenic bacteria strongly up-regulated the expression of antimicrobial chemokines and proinflammatory mediators, whereas the red-complex bacteria stimulated low levels, or often suppressed, expression of these factors. Regarding the regulation of AMPs, the inhibition of HBD3, HBD106 and HBD107 mRNAs by Porphyromonas gingivalis was noticeable; however, differences between the two bacterial groups were not conspicuous. Differential degradation of proteins by the six bacterial species was observed: P. gingivalis and Treponema denticola degraded proteins well, whereas the other species degraded proteins to a relatively lower degree. CONCLUSION: The invasion of red-complex bacteria into gingival connective tissue can suppress the immune response of GFs and can be a source of persistent infection in connective tissue.

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

BACKGROUND: There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. METHODS: Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. RESULTS: A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m2 or above) predicted clinically relevant POPF. CONCLUSION: External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov).

Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?

PURPOSE: To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model. RESULTS: On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(-), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasis-free survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained (p = 0.2940). Tumor location was the only independent prognostic factor predicting OS (p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS (p = 0.0030, 0.0013, and 0.0037, respectively). CONCLUSIONS: This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets.

Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig-to-nonhuman primate (NHP) model has not been demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen-free (DPF) miniature pigs and infused intraportally into streptozotocin-induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti-thymocyte globulin (ATG) induction and maintenance with anti-CD154 monoclonal antibody and low-dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90-110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow-up period showed excellent glucose disposal capacity and porcine C-peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.

Evaluation of in vivo antitumor effects of ANT2 shRNA delivered using PEI and ultrasound with microbubbles.

Gene therapy using RNA interference can be directed against tumors through various strategies, but has been hindered owing to the inefficiency of non-viral delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2 (ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the polyethylenimine (PEI) and an ultrasound gene delivery method, human breast carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL-2Rγ(null)) mice. The results showed greater tumor regression (*P<0.05) as well as an increased survival rate in the group receiving ANT2 shRNA+two types of enhancer relative to the groups receiving ANT2 shRNA without enhancer. These findings demonstrate that the introduction of PEI and ultrasound with SonoVue exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI and ultrasound provided the best results with respect to tumor regression, the antitumor effects from the individual enhancers were approximately equivalent. In addition, we confirmed that there was no toxicity on aspartate aminotransferase and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen or creatine kinase levels in the kidney following the various gene delivery methods.

Portal vein patency after pancreatoduodenectomy for periampullary cancer.

BACKGROUND: The fate of the portal vein (PV) after pancreatoduodenectomy, especially its long-term patency and associated complications, has received little attention. The aim of this study was to explore the long-term patency rate of the PV after pancreatoduodenectomy, focusing on risk factors for PV stenosis/occlusion and associated complications. METHODS: Serial CT images of patients who underwent pancreatoduodenectomy for periampullary cancer between January 2000 and June 2012 in a single institution were evaluated for PV stenosis or occlusion. RESULTS: A total of 826 patients were enrolled. The PV stenosis/occlusion rate after pancreatoduodenectomy was 19.6 per cent and the 5-year patency rate 69.9 per cent. The most frequent cause of PV stenosis/occlusion was local recurrence followed by postoperative change and PV thrombosis. Patients who underwent PV resection had a higher PV stenosis/occlusion rate than those who did not (51 versus 17.4 per cent; P < 0.001). The 3-year patency rate was highest in patients with cancer of the ampulla of Vater and lowest in patients with pancreatic cancer (91.9 versus 55.5 per cent respectively; P < 0.001). Multivariable analysis showed that risk factors for PV stenosis/occlusion included primary tumour location, chemoradiotherapy and PV resection. PV stenosis or occlusion without disease recurrence was observed in 17.3 per cent of the patients. PV resection and grade B or C pancreatic fistula were independent risk factors for PV stenosis/occlusion. Among 162 patients with PV stenosis or occlusion, five (3.1 per cent) had fatal recurrent gastrointestinal bleeding. CONCLUSION: PV stenosis or occlusion is common after pancreatoduodenectomy, particularly if the PV has been resected and/or chemoradiotherapy was given after surgery. Although recurrence is the most frequent cause of PV stenosis/occlusion, this complication is found in a significant proportion of patients without disease recurrence.

Staging accuracy of endoscopic ultrasound performed by nonexpert endosonographers in patients with resectable esophageal squamous cell carcinoma: is it possible?

The accuracy of endoscopic ultrasound (EUS) is operator-dependent. According to learning curve study, the accuracy of EUS T-staging for esophageal cancer has been reported to be greater in an investigator who had performed at least 100 EUS examinations. We determined comparative study regarding T-staging accuracy of EUS for esophageal squamous cell carcinoma between expert and nonexpert endoscopic ultrasonographers. We retrospectively identified 73 consecutive patients with esophageal squamous cell carcinoma who underwent EUS and endoscopic mucosal resection, endoscopic submucosal dissection, or surgery. EUS was performed by expert (Group 1) and nonexpert (Group 2) endoscopic ultrasonographers in multitertiary hospitals. Groups 1 and 2 were 37 and 36 patients during 2005-2011, respectively. Forty-two patients (57.5%) of the overall patients underwent surgical exploration. Correct endoscopic ultrasonographic T-staging of Group 1 was observed in 34 (91.9%) patients, while that of Group 2 was observed in 26 (72.2%) patients. And there was significant difference in correct endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.035). The incorrect endoscopic ultrasonographic T-staging of Group 1 were three cases that were overstaging (8.1%), but in Group 2 there were seven overstaging (19.4%) and three understaging (8.3%). There was no significant difference in overstaging or understaging of incorrect endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.528). This study first provides evidence that endoscopic ultrasonographic T-staging of nonexpert endoscopic ultrasonographers was inferior to be correct, compared with that of expert endoscopic ultrasonographers. EUS staging for esophageal cancer should be performed by expert endoscopic ultrasonographers to provide appropriate management strategy.

Relative adrenal insufficiency in chronic liver disease: its prevalence and effects on long-term mortality.

BACKGROUND: The relationship between relative adrenal insufficiency (RAI) and chronic liver disease is unclear. AIM: To determine the frequency with which RAI is observed in noncritically ill patients at various stages of chronic liver disease, and the correlation between RAI and disease severity and long-term mortality. METHODS: In total, 71 non-critically ill patients with liver cirrhosis (n = 54) and chronic hepatitis (n = 17) were evaluated prospectively. A short stimulation test (SST) with 250 µg of corticotrophin was performed to detect RAI. RAI was defined as an increase in serum cortisol of <9 µg/dL in patients with a basal total cortisol of <35 µg/dL. RESULTS: RAI was observed in only 13 (24.1%) of 54 patients with cirrhosis. Compared to those without RAI, cirrhotic patients with RAI had significantly higher Child-Turcotte-Pugh score (10.3 ± 1.7 vs. 7.1 ± 1.8, mean ± s.d., P < 0.001) and Model for End-Stage Liver Disease score (14.5 ± 6.6 vs. 9.4 ± 3.7, P = 0.017). The cortisol response to corticotropin was negatively correlated with the severity of cirrhosis (P < 0.05). In addition, the mortality rate was higher in cirrhotic patients with RAI (69.2%) than in those without RAI (4.9%; P < 0.001) during the follow-up period of 20.1 ± 13.5 months (range, 5.8-51.1 months). The cumulative 1-year survival rates in cirrhotic patients with and without RAI were 69.2% and 95.0%, respectively (P = 0.05), while the corresponding cumulative 3-year survival rates were 0% and 95.0% (P < 0.001). CONCLUSIONS: Relative adrenal insufficiency is more commonly observed in those with severe cirrhosis, and is clearly associated with more advanced liver disease and a shortened long-term survival. This suggests that relative adrenal insufficiency is an independent prognostic factor in non-critically ill patients with cirrhosis.

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

BACKGROUND: 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. METHODS: A prospectively collected database of patients with biopsy-proven BD-IPMN was analysed to compare factors between the first and second consensus guidelines, particularly as predictors of malignancy. RESULTS: Of 350 patients with BD-IPMN, sensitivity (0.724) and balanced accuracy (0.751) of the second guidelines were superior to those (0.639 and 0.730) in the first version at the expense of slightly reduced specificity (0.779 versus 0.822 for the first version) by random forest models. Multiple logistic regression analysis showed that main pancreatic duct dilatation greater than 5 mm (hazard ratio (HR) 4.54, 95 per cent confidence interval 2.45 to 8.41; P < 0.001), mural nodules (HR 6.27, 3.27 to 12.01; P < 0.001) and carbohydrate antigen 19-9 level above 37 units/ml (HR 4.03, 1.83 to 8.90; P = 0.001) were independent predictors of BD-IPMN malignancy. CONCLUSION: The new consensus guidelines provide better sensitivity, performance of factors predicting malignancy, and balanced accuracy in the diagnosis of BD-IPMN malignancy. Size alone was limited in predicting malignancy. Variability in clinical significance of the individual factors associated with a risk of malignancy indicates the need for a tailored approach in the management of patients with BD-IPMN.

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

BACKGROUND: 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. METHODS: Consecutive patients undergoing pancreaticoduodenectomy or distal pancreatectomy between 2007 and 2011 were included. Relative bodyweight (RBW), triceps skinfold thickness (TSFT), serum protein, albumin, transferrin, fasting blood glucose, postprandial 2-h glucose (PP2), glycosylated haemoglobin A1c and stool elastase measurements, and European Organization for Research and Treatment of Cancer QLQ-C30 questionnaires were collected serially for 1 year. RESULTS: Some 136 patients undergoing pancreatic resection completed the study. RBW and TSFT recovered to over 90 per cent of the preoperative value by 12 months, whereas transferrin, albumin and protein had returned to preoperative levels by 3 months. Diabetes mellitus, impaired fasting glucose or raised PP2 was present in 42 of 76 patients at 6 months and 36 of 76 at 12 months. Although steatorrhoea and diarrhoea had mainly resolved by 3 months, stool elastase level decreased after operation and showed no recovery. Nutritional status, pancreatic endocrine function and QoL returned to preoperative levels in 63 (46·3 per cent), 72 (52·9 per cent) and 77 (56·6 per cent) of 136 patients within 6 months of pancreatectomy. Multivariable analysis revealed that age 60 years or more, operation type, chronic pancreatitis and malignant disease had a significant impact on nutritional index, pancreatic function and QoL. CONCLUSION: About half of all patients can expect recovery from pancreatectomy after 6 months, but those with risk factors need more careful follow-up and supportive management.

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

PURPOSE: Rapidly 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. METHODS: Bile 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. RESULTS: The five most frequently isolated microorganisms were Enterococcus (22.7 %) followed by Escherichia (13.2 %), Pseudomonas (10.9 %), Klebsiella (10.3 %), and Enterobacter (7.2 %). The trend in annual incidence indicated a growing emergence of Enterococcus (P < 0.001). Among Enterococcus, E. faecium acquired a dominant position (50.6 %), showing an increasing trend over the study period (P = 0.026). The incidence of vancomycin-resistant Enterococcus also showed an increasing trend (P < 0.001). 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 (P = 0.001 and P = 0.027, respectively). CONCLUSIONS: In 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.