Prognostic value of preoperative protein-induced vitamin K absence or antagonist II after liver resection for hepatitis B-related hepatocellular carcinoma: a nationwide multicenter study.

Purpose: Although protein-induced vitamin K absence or antagonist II (PIVKA-II) has been used as a diagnostic tool for hepatocellular carcinoma (HCC), its prognostic value remains unclear. Methods: This was a nationwide multicenter study using the database of the Korean Liver Cancer Association. Patients with hepatitis B-related HCC who underwent liver resection as the first treatment after initial diagnosis (2008-2014) were selected randomly. Propensity score matching (1:1) was performed for comparative analysis between those with low and high preoperative PIVKA-II. Univariable and multivariable Cox proportional-hazards regression were used to identify prognostic factors for HCC-specific survival. Results: Among 6,770 patients, 956 patients were included in this study. After propensity score matching, the 2 groups (n = 245, each) were well balanced. The HCC-specific 5-year survival rate was 80.9% in the low PIVKA-II group and 78.7% in the high PIVKA-II group (P = 0.605). In univariable analysis, high PIVKA-II (>106.0 mAU/mL) was not a significant predictor for worse HCC-specific survival (hazard ratio [HR], 1.183; 95% confidence interval [CI], 0.76-1.85; P = 0.461). In multivariable analysis, hyponatremia of <135 mEq/L (HR, 4.855; 95% CI, 1.67-14.12; P = 0.004), preoperative ascites (HR, 4.072; 95% CI, 1.59-10.43; P = 0.003), microvascular invasion (HR, 3.112; 95% CI, 1.69-5.74; P < 0.001), and largest tumor size of ≥5.0 cm (HR, 2.665; 95% CI, 1.65-4.31; P < 0.001), but not preoperative high PIVKA-II, were independent predictors for worse HCC-specific survival. Conclusion: Preoperative PIVKA-II is not an independent prognostic factor for HCC-specific survival after liver resection for hepatitis B-related HCC.

Prognosis of pancreatic head cancer with different patterns of lymph node metastasis.

BACKGROUND: The nodal stage of pancreatic ductal adenocarcinoma (PDAC) is revised in the AJCC 8th edition. Studies on the prognosis of PDAC according to lymph node metastasis (LNM) are still ongoing. We attempted to find the patterns of nodal involvement and to reveal its clinical significance to overall survival (OS). METHODS: We analyzed 585 patients who received pancreatic head cancer surgery diagnosed as PDAC from January 2007 to December 2016. Patients were classified into three groups: Group 1 (G1, patients without LNM), Group 2 (G2, those with LNM only in the peripancreatic area), and Group 3 (G3 those with LNM in the other area and/or peripancreatic LNM). Risk factors were analyzed by Cox-regression test and overall survival was compared by Kaplan-Meier analysis. RESULTS: LNM in peripancreatic area was the most common (88.7%). In the multivariate analysis, T stage, nuclear differentiation, adjuvant treatment, and the G2 and G3 were independent risk factors for OS (G2 over G1, HR 1.384, 95% CI 1.046-1.802; P = .036 and G3 over G1, HR 2.383, 95% CI 1.378-4.103; P = .001). G3 showed worse OS than G2 (P = .006). In the N1 status, LNM to the pericholedochal (PC) and superior mesenteric artery (SMA) areas resulted in worse OS than the G2 (P = .011 and P = .019). CONCLUSIONS: We found that LNM beyond the peripancreatic area significantly affects OS in pancreatic head cancer patients. Depending on the station of the LNM, different risk-stratification and treatment strategies will need to be considered.

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.

Long term clinical outcomes of portal vein stenting for symptomatic portal vein stenosis after pancreaticoduodenectomy.

ABSTRACT: Gastrointestinal bleeding caused by portal vein (PV) stenosis is serious complication after pancreaticoduodenectomy (PD) The purpose of this study is to reveal the long-term clinical outcomes of PV stenting for symptomatic PV stenosis and risk factors of stent related complication.Fifteen patients who underwent portal vein stenting for symptomatic PV stenosis after PD between 2000 and 2018 were retrospectively reviewed. The whole cohort was divided into 9 patients with benign stenosis group (Group-B) and 6 patients with recurrence group (Group-R).The median follow up period was 17.0 (interquartile range 12.0-38.0) months. The technical success rate and clinical success rate was revealed at 93.3% and 86.7%. The primary patency rate of stents was 79.4% and mean patency period was 14.0 (4.0-28.0) months. There was significant difference in time to stenosis and proportion of anticoagulation treatment between 2 groups [2.0 (1.0-4.0) months vs 18.5 (2.5-50.3) months, P  = .035 and 100% vs 50%, P  = .044. In univariable analysis, stent diameter was found to have a significant correlation with stent occlusion (P  = .036).PV stenting was found to be feasible and safe in the treatment of symptomatic PV stenosis from a long term point of view.

The impact of portal vein resection on outcome of hilar cholangiocarcinoma.

BACKGROUNDS/AIMS: Portal vein resection (PVR) with major hepatic resection can increase the rate of curative resection for hilar cholangiocarcinoma (HC). However, the oncologic role and safety of PVR is still debatable. This study aims to analyze PVR in terms of safety and therapeutic effectiveness. METHODS: We retrospectively analyzed 235 patients who had undergone major hepatic resection for HC with curative intent, including patients with PVR (PVR, n=35) consisting of PV invasion (PVR-A, n=9), No PV invasion (PVR-B, n=26); and patients without PVR (No PVR, n=200). RESULTS: There was no significant difference in the 30-day mortality or postoperative morbidity between PVR and No PVR (2.9% vs. 1.0%; p=0.394 and 34.3% vs. 35.0%; p=0.875). The rate of advanced HC (T3: 40% vs. 12%; p<0.001 and nodal metastasis: 60% vs. 28%; p<0.001) was higher in PVR compared to No PVR. There was no significant difference in the 5-year overall survival rates and disease-free survival between PVR-A vs. PVR-B vs. No PVR. In multivariate analysis, estimated blood loss >600 ml (p=0.010), T3 diseases (p=0.001), nodal metastasis (p=0.001) and poor differentiation (p=0.002) were identified as independent risk factors for survival. CONCLUSIONS: PVR does not increase postoperative mortality or morbidity. It showed a similar oncologic outcome, despite a more advanced disease state in patients with HC. Given these findings, PVR should be actively performed if necessary, after careful patient selection.

Optimal stapler cartridge selection to reduce post-operative pancreatic fistula according to the pancreatic characteristics in stapler closure distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is associated with potentially fatal complications, but there is lack of data on relationship between pancreas thickness, and stapler size and the POPF rate. This study aimed to suggest optimal stapler that reduces POPF rate according to the pancreas thickness. METHODS: This retrospective cohort study was conducted in two tertiary high-volume pancreas centers. 599 patients who underwent distal pancreatectomy were assessed for stump reinforcement methods, pathology findings, pancreas thickness, and cartridge used. The cartridges were grouped as I, II, III according to the closed height ≤1.5 mm, 1.8 mm, and ≥2.0 mm, respectively. RESULTS: The POPF rate increased according to the thickness. The stapler Groups I, II, and III had an overall POPF rate of 66.4% vs. 61.7% vs. 57.8%, but Group II stapler cartridge showed a significant reduction in the POPF rate than other cartridges in pancreas with thickness <13 mm (53.5% vs. 21.7% vs. 36.0%, p = 0.031). There was no significant difference between the POPF rate according to stapler groups when the pancreas was thicker than 13 mm. CONCLUSION: Thickness is the strongest risk factor in predicting POPF. Use of Group II stapler cartridge for pancreas with a thickness of <13 mm can help reduce POPF.

Appraisal of 5-year recurrence-free survival after surgery in pancreatic ductal adenocarcinoma.

BACKGROUND/PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is regarded as incurable, with a limited survival rate after curative resection. The aim of this study was to explore long-term survival and late recurrence of PDAC after surgery. METHODS: Medical data of 859 patients who underwent resection between 1995 and 2014 were retrospectively examined. The clinicopathological features of the 5-year recurrence-free survivors and the patients with recurrent disease after 5 years were investigated separately. RESULTS: Among the 768 patients who were finally included in this study, elevated CA 19-9, tumor size, poor differentiation, and positive lymph node metastasis were associated with recurrence. In 89 patients with 5-year RFS, age, tumor size, differentiation, and lymph node metastasis were statistically significant predictive factors. Among these patients, disease relapse occurred in 11 patients; age was the only difference compared to those who remained free of recurrence. CONCLUSIONS: Most prognosticators failed to predict the risk of recurrence in the 5 years following surgery for PDAC, and recurrence can occur even at time points up to 100 months. Therefore, cure of PDAC cannot be guaranteed by a 5-year recurrence-free interval, and further studies into the inherent nature of PDAC are needed to develop adequate surveillance systems which may lead to improvements in survival.

National survey of Korean hepatobiliary-pancreatic surgeons on attitudes about the enhanced recovery after surgery protocol.

BACKGROUNDS/AIMS: The purpose of this study was to investigate attitudes regarding the Enhanced Recovery After Surgery (ERAS) protocol of hepato-biliary-pancreatic (HBP) surgeons in Korea and the extent to which they use the protocol for perioperative management. METHODS: An online survey was conducted among members of the Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS) for eight weeks beginning on August 2019. The questionnaire, which was written in Korean, was based on the latest ERAS guidelines. Total responses were collected from 127 surgeons. RESULTS: Of the 127 total respondents, the largest proportion (44.9%) were working in Seoul. In terms of established in-hospital clinical pathways (CP), 19.7% of the participating surgeons had and followed a CP in pancreaticoduodenectomy (PD) and 21.3% in hepatectomy. Regarding the ERAS protocol for each surgery, four items (18.2%) regarding PD and seven items (35.0%) related to hepatectomy were followed by more than 50% of respondents. CONCLUSIONS: ERAS guidelines are one of the consensuses for better recovery in perioperative management of patients undergoing major surgeries and encompass the overall process of patient recovery including patient education, pain control, physiologic balance, and perioperative nutrition. A novel project is needed to successfully implement an evidence-based enhanced recovery strategy.

Proposed Modification of Staging for Distal Cholangiocarcinoma Based on the Lymph Node Ratio Using Korean Multicenter Database.

The 8th American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (DCC) included a positive lymph node count (PLNC), but a comparison of the prognostic predictive power of PLNC and lymph node ratio (LNR) is still under debate. This study aimed to compare various staging models made by combining the abovementioned factors, identify the model with the best predictive power, and propose a modified staging system. We retrospectively reviewed 251 patients who underwent surgery for DCC at four centers. To determine the superiority of various staging models for predicting overall OSR, Akaike information criterion (AIC), Bayesian information criterion (BIC), AIC correction (AICc), and Harrell's C-statistic were calculated. In multivariate analysis, age (p = 0.003), total lymph node count (p = 0.033), and revised T(LNR)M staging (p < 0.001) were identified as independent factors for overall survival rate. The predictive performance of revised T (LNR) M staging (AIC: 1288.925, BIC: 1303.377, AICc: 1291.52, and Harrell's C statics: 0.667) was superior to other staging system. A modified staging system consisting of revised T category and LNR predicted better overall survival of DCC than AJCC 7th and AJCC 8th editions. In the future, external validation of the proposed new system using a larger cohort will be required.

Recurrence After Resection for Intraductal Papillary Neoplasm of Bile Duct (IPNB) According to Tumor Location.

BACKGROUND: No studies have yet analyzed the characteristics of recurrence after resection for intraductal papillary neoplasm of bile duct (IPNB) based on tumor location. We analyzed the patterns, timing, and risk factors for recurrence. METHODS: From 1994 to 2014, data from 103 patients who were diagnosed with IPNB were retrospectively reviewed. Among these, 44 were extrahepatic IPNB (E-IPNB) and 59 were intrahepatic IPNB (I-IPNB). RESULTS: CK20, pancreaticobiliary type, tumor invasion beyond ductal wall, tumor invasion to adjacent organs, and invasive disease were more frequently found in E-IPNB than in I-IPNB (22.7 vs. 8.5%; p = 0.043, 38.6 vs. 23.7%; p = 0.050, 20.5 vs. 11.9%; p < 0.001, 4.5 vs. 1.7%; p < 0.001 and 93.2 vs. 55.9%; p < 0.001). E-IPNB has poorer 5-year recurrence-free survival (RFS) compared to I-IPNB (51.7 vs. 91.4%; p < 0.001). There was no significant difference in the rate of initial isolated locoregional recurrence and initial distant recurrence according to tumor location (14.6 in E-IPNB vs. 3.0% in I-IPNB; p = 0.123, 19.5 in E = IPNB vs. 12.0% in I-IPNB; p = 0.136). Recurrence rate according to timing was different between E-IPNB and I-IPNB: within 1 year (33.3% vs. 83.3%; p = 0.061) and 1-3 years (50.0% vs. 0%; p = 0.052). The independent prognostic factors for RFS were tumor location (p = 0.034) and lymph node metastasis (p = 0.013). CONCLUSIONS: E-IPNB has a worse prognosis than I-IPNB. Different follow-up schedules for surveillance according to tumor location are needed after surgery.

Long-term clinical outcomes after endovascular management of ruptured pseudoaneurysm in patients undergoing pancreaticoduodenectomy.

PURPOSE: Recent studies have analyzed the short-term clinical outcomes of ndovascular management. However, the long-term outcomes are unknown. This study aimed to investigate clinical outcomes after endovascular management for ruptured pseudoaneurysm in patients after pancreaticoduodenectomy (PD). METHODS: The medical records of 2,783 patients who underwent PD were retrospectively reviewed at a single center. Of 62 patients who received intervention after pseudonaeurysm rupture, 57 patients (91.9%) experienced eventual success of hemostasis. The patients were composed as follows: (embolization only [EMB], n = 30), (stent-graft placement only [STENT], n = 19) and (both embolization and stent-graft placement simultaneously or different times [EMB + STENT], n = 8). Long-term complications were defined as events that occur more than 30 days after the last successful endovascular treatment. RESULTS: Among 57 patients, short-term stent-graft related complications developed in 3 patients (5.3%) and clinical complication developed in 18 patients (31.5%). Nine (15.8%) had long-term stent-graft related complications, which involved partial thrombosis in 5 cases, occlusion in 3 cases and migration in 1 case. Except for 1 death, the remaining 8 cases did not experience clinical complications. The stent graft primary patency rate was 88.9% after 1 month, 84.2% after 1 year, and 63.2% after 2 years. Of 57 patients, 30 days mortality occurred in 8 patients (14.0%). CONCLUSION: After recovery from initial complication, most of patients did not experience fatal clinical complication during long-term follow-up. Endovascular management is an effective and safe management of pseudoaneurysm rupture after PD in terms of long-term safety.

Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

Nomogram for predicting postoperative pancreatic fistula.

BACKGROUND: Previous studies analyzed risk factors for postoperative pancreatic fistula (POPF) and developed risk prediction tool using scoring system. However, no study has built a nomogram based on individual risk factors. This study aimed to evaluate individual risks of POPF and propose a nomogram for predicting POPF. METHODS: From 2007 to 2016, medical records of 1771 patients undergoing pancreaticoduodenctomy were reviewed retrospectively. Variables with p < 0.05 in multivariate logistic regression analysis were included in the nomogram. Internal performance validation was executed using a repeated cross validation method. RESULTS: Of 1771 patients, 222 (12.5%) experienced POPF. In multivariable analysis, sex (p = 0.004), body mass index (BMI) (p < 0.001), ASA score (p = 0.039), preoperative albumin (p = 0.035), pancreatic duct diameter (p = 0.002), and location of tumor (p < 0.001) were identified as independent predictors for POPF. Based on these six variables, a POPF nomogram was developed. The area under the curve (AUC) estimated from the receiver operating characteristic (ROC) graph was 0.709 in the train set and 0.652 in the test set. CONCLUSIONS: A POPF nomogram was developed. This nomogram may be useful for selecting patients who need more intensified therapy and establishing customized treatment strategy.

Clinical significance of revised microscopic positive resection margin status in ductal adenocarcinoma of pancreatic head.

PURPOSE: Recent studies have suggested microscopic positive resection margin should be revised according to the presence of tumor cells within 1mm of the margin surface in resected specimens of pancreatic cancer. However, the clinical meaning of this revised margin status for R1 resection margin was not fully clarified. METHODS: From July 2012 to December 2014, the medical records of 194 consecutive patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head were analyzed retrospectively. They were divided into 3 groups on margin status; revised microscopic negative margin (rR0) - tumor exists more than 1 mm from surgical margin, revised microscopic positive margin (rR1) - tumor present within less than 1 mm from surgical margin, classic microscopic positive margin (cR1) - tumor is exposed to surgical margin. RESULTS: There were 76 rR0 (39.2%), 100 rR1 (51.5%), and 18 cR1 (9.3%). There was significant difference in disease-free survival rates between cR1 vs. rR1 (8.4 months vs. 24.0 months, P = 0.013). Margin status correlated with local recurrence rate (17.1% in rR0, 26.0% in rR1, and 44.4% in cR1, P = 0.048). There is significant difference in recurrence at tumor bed (11.8% in rR0 vs. 23.0 in rR1, P = 0.050). Of rR1, adjuvant treatment was found to be an independent risk factor for local recurrence (hazard ratio, 0.297; 95% confidence interval, 0.127-0.693, P = 0.005). CONCLUSION: Revised R1 resection margin (rR1) affects recurrence at the tumor bed. Adjuvant treatment significantly reduced local recurrence of rR1. Accordingly, adjuvant chemoradiation for rR1 group should be taken into account.