Optimal timing of portal vein embolization (PVE) after preoperative biliary drainage for hilar cholangiocarcinoma.

BACKGROUND: Preoperative biliary drainage (PBD) followed by portal vein embolization (PVE) has increased the chance of resection for hilar cholangiocarcinoma (CCC). We aim to identify the optimal timing of PVE after PBD in patients undergoing hepatectomy for hilar CCC. METHODS: We retrospectively reviewed 64 patients who underwent hepatectomy after PBD and PVE for hilar CCC. The patients were classified into 3 groups: Group 1 (PBD-PVE interval ≤7 days), Group2 (8-14 days) and Group 3 (>14 days). The primary end points were 90 days mortality and grade B/C posthepatectomy liver failure (PHLF). RESULTS: There was no significant difference in primary end points between three groups. A marginally significant difference was found in the incidence of Clavien-Dindo grade ≥3 complications and wound infection (57.1% vs 38.1% vs 72.4%, p = 0.053 and 21.4% vs 38.1% vs 55.2%, p = 0.099). In multivariable analysis, Bismuth type IIIb or IV was independent risk factors for grade B/C PHLF (HR: 4.782, 95% CI 1.365-16.759, p = 0.014). CONCLUSIONS: Considering that the PBD-PVE interval did not affect PHLF, and the surgical complications increased as the interval increases, PVE as early as possible after PBD would be beneficial.

The effects of sarcopenia and sarcopenic obesity after pancreaticoduodenectomy in patients with pancreatic head cancer.

BACKGROUND: Recently, several studies have reported that sarcopenia and sarcopenic obesity (SO) could worsen postoperative complications after PD. This study aims to evaluate the effects of preoperative sarcopenia and SO following PD in pancreatic head cancer (PHD). METHODS: Preoperative sarcopenia and SO were assessed in 548 patients undergoing PD for PHC at Samsung Medical Centre between 2007 and 2016. The visceral adipose tissue-to-skeletal muscle ratio was calculated from cross-sectional visceral fat and muscle areas on preoperative CT images. The overall survival (OS) and rate of clinically relevant postoperative pancreatic fistula (CR-POPF) among postoperative complications were extracted from prospectively maintained databases. RESULTS: Preoperative sarcopenia was present in 252 patients (45.9%). The 5-year survival rates of patients with non-sarcopenia and sarcopenia were 28.4% and 23.4% (p = 0.046). Preoperative SO was present in 202 patients (36.9%). After multivariable analysis, the presence of SO was the only independent risk factor for CR-POPF (p = 0.018). CONCLUSION: Sarcopenia can be a risk factor affecting decreased OS after PD in patients with PHC. SO is the only predictive factor for CR-POPF after PD in patients with PHC. More observational studies are needed to evaluate the effects of sarcopenia and SO on survival after PD.

Validating a simple scoring system to predict malignancy and invasiveness of intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The objective of the present study was to identify reliable preoperative factors predicting malignancy or invasiveness of intraductal papillary mucinous neoplasm (IPMN) of the pancreas and the effectiveness of a diagnostic scoring system based on these factors. METHODS: Between August 1994 and December 2007, 204 patients underwent pancreatic resection for IPMN at a single institute. Medical records were reviewed retrospectively, and a new diagnostic scoring system for predicting malignant IPMN preoperatively was designed. RESULTS: Univariate analysis revealed nine significant predictors of both malignant and invasive IPMN: age > or =60 years, history of pancreatitis, presence of mural nodule(s), diameter of main pancreatic duct (MPD) >6 mm, main duct or mixed type, total bilirubin >1.2 mg/dl, CA-19-9 >37 U/ml, tumor location in the pancreatic head, and tumor size >30 mm. Multivariate analysis showed that age, pancreatitis, mural nodule(s), and MPD diameter were independent predictors of invasive IPMN, and that all these parameters, plus elevated carbohydrate antigen-19-9 (CA-19-9), were independent predictors of malignant IPMN. A scoring system based on these five factors, each assigned 1 point, and with a cut-off of 3 points, could predict malignant IPMN with a sensitivity of 50.7% and a specificity of 90.1%. The 5-year survival rates of patients with benign and malignant IPMN were 95.0% and 64.0%, respectively. CONCLUSIONS: Our scoring system using five independent factors (age > or =60 years, history of pancreatitis, presence of mural nodule(s), elevated level of CA-19-9, and MPD diameter >6 mm) may be helpful for predicting malignancy and postoperative survival.

Prediction of response of mutated alpha-galactosidase A to a pharmacological chaperone.

OBJECTIVE: To examine the relationship between types and locations of mutations of the enzyme alpha-galactosidase (Gal) A in Fabry disease and the response to the pharmacological chaperone 1-deoxygalactonojirimycin (DGJ). METHODS: T cells grown from normal individuals or from patients with Fabry disease were tested for response to treatment with DGJ by increased activity of alpha-Gal A. RESULTS: Cells from normal controls responded with a 28% increase in alpha-Gal A activity, whereas response in Fabry individuals was mutation dependent ranging from no increase to fully normal activity. Nine truncation mutations (all nonresponsive) and 31 missense mutations were tested. Three groups of missense mutations were categorized: responders with activity more than 25% of normal, nonresponders, with less than 7% and an intermediate response group. In normal cells and in responders an increase in the mature lysosomal form of alpha-Gal A was observed after DGJ treatment. Nonresponders showed little or no protein with or without DGJ. The intermediate response group showed an increase in band intensity but incomplete processing of the enzyme to the mature form. CONCLUSION: Mapping the missense mutations to the structure of alpha-Gal A identified several factors that may influence response. Mutations in regions that are not in alpha-helix or beta-sheets, neither involved in disulfide bonds nor with an identified functional or structural role were more likely to respond. Predictability is, however, not precise and testing of each mutation for response to pharmacological chaperone therapy is necessary for Fabry disease and related lysosomal storage disorders.