Conversion surgery for initially unresectable locally advanced biliary tract cancer: A multicenter collaborative study conducted in Japan and Korea.

BACKGROUND: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. METHODS: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. RESULTS: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%. CONCLUSIONS: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required.

Neoadjuvant Therapy for Extrahepatic Biliary Tract Cancer: A Propensity Score-Matched Survival Analysis.

Background: Although surgery is the mainstay of curative-intent treatment for extrahepatic biliary tract cancer (EBTC), recurrence following surgery can be high and prognosis poor. The impact of neoadjuvant therapy (NAT) relative to upfront surgery (US) among patients with EBTC remains unclear. Methods: The Surveillance, Epidemiology, and End Results (SEER) databases was utilized to identify patients who underwent surgery from 2006 to 2017 for EBTC, including gallbladder cancer (GBC) and extrahepatic cholangiocarcinoma (ECC). Trends in NAT utilization were investigated, and the impact of NAT on prognosis was compared with US using a propensity score-matched (PSM) analysis. Results: Among 6582 EBTC patients (GBC, n = 4467, ECC, n = 2215), 1.6% received NAT; the utilization of NAT for EBTC increased over time (Ptrend = 0.03). Among patients with lymph node metastasis, the lymph node ratio was lower among patients with NAT (0.18 vs. 0.40, p < 0.01). After PSM, there was no difference in overall survival (OS) and cancer-specific survival (CSS) among patients treated with NAT versus US (5-year OS: 24.0% vs. 24.6%, p = 0.14, 5-year CSS: 38.0% vs. 36.1%, p = 0.21). A subgroup analysis revealed that NAT was associated with improved OS and CSS among patients with stages III-IVA of the disease (OS: HR 0.65, 95%CI 0.46-0.92, p = 0.02, CSS: HR 0.62, 95%CI 0.41-0.92, p = 0.01). Conclusions: While NAT did not provide an overall benefit to patients undergoing surgery for EBTC, individuals with advanced-stage disease had improved OS and CSS with NAT. An individualized approach to NAT use among patients with EBTC may provide a survival benefit.

Trends and Variations in Drain Use Following Pancreatoduodenectomy: Is Early Drain Removal Becoming More Common?

BACKGROUND: Although previous studies have noted the potential benefit of early drain removal (EDR) after pancreatoduodenectomy (PD), there is a paucity of data on the timing of drain removal utilizing a national database that reflect the "real world" setting. Given the ongoing controversy related to PD drain use and management, we sought to define trends in drain use among a large national cohort, as well as identify factors associated with EDR following PD. METHODS: The ACS NSQIP targeted pancreatectomy database was used to identify patients who underwent PD between 2014 and 2020. The trend in proportion of patients with EDR (removal ≤ POD3) as well as predictors of EDR were assessed. Risk-adjusted postoperative outcomes were evaluated by multivariable regression analysis. RESULTS: Among 14,356 patients, 16.2% of patients (N = 2324) experienced EDR, and the proportion of patients with EDR increased by 68% over the study period (2014: 10.9% vs. 2020: 18.3%, p < 0.001). Higher drain fluid amylase on POD1-3 [LogWorth (LW) = 44.3], operative time (LW = 33.2), and use of minimally invasive surgery (LW = 14.0) were associated with EDR. Additionally, EDR was associated with decreased risk of overall and serious morbidity, PD-related morbidity (e.g., pancreatic fistula), reoperation, prolonged length of stay and readmission (all p < 0.05). CONCLUSIONS: Routine drain placement remains a common practice among most surgeons. EDR following PD increased over time was associated with lower post-operative complications and shorter LOS. Despite evidence that EDR was safe and may even be associated with lower complications, only 1 in 6 patients were managed with EDR.

Glasgow Prognostic Score Predicts Survival and Recurrence Pattern in Patients With Hepatocellular Carcinoma After Hepatectomy.

BACKGROUND/AIM: The prognostic significance of the Glasgow Prognostic Score (GPS) on outcomes of liver resection for hepatocellular carcinoma (HCC) remains unclear; the aim of the study was to assess its significance. PATIENTS AND METHODS: A total of 480 patients with HCC who underwent liver resection with curative intent at the Yokohama City University Hospital and Medical Center were enrolled in the study. Patients were classified into three groups: GPS-0, C-reactive protein (CRP) ≤1.0 mg/dl serum albumin ≥3.5 g/dl; GPS-1, CRP >1.0 mg/dl or serum albumin <3.5 g/dl; and GPS-2, CRP >1.0 mg/dl, serum albumin <3.5 g/dl. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analyzed retrospectively. The recurrence pattern was also investigated using GPS. RESULTS: Of the 480 patients, 382 (79.6%), 81 (16.9%), and 17 (3.5%) were assigned to GPS-0, GPS-1, and GPS-2, respectively. Elevated GPS, indocyanine green retention rate at 15 min, and protein induced by vitamin K antagonist-II (PIVKA-II) were significantly associated with a poor OS. Elevated GPS, alpha-fetoprotein, and PIVKA-II were significantly associated with a poor DFS by multivariate analysis. The number of patients with liver-only recurrence in GPS-0, GPS-1, and GPS-2 was 179 (86.1%), 40 (78.4%), and 9 (69.2%), respectively. The number of patients with four or more intrahepatic metastases in the GPS-0, GPS-1, and GPS-2 groups, was 33 (17.9%), 11 (27.5%), and 8 (88.9%), respectively. The number of patients with four or more intrahepatic metastases in the GPS-2 group was significantly higher (p<0.001). CONCLUSION: Preoperative GPS is a useful predictor of OS and recurrence pattern after liver resection with a curative intent for HCC.

Prognostic markers including immune and inflammatory factors predict outcomes in patients receiving postoperative radiation therapy for cholangiocarcinoma.

PURPOSE: This study aimed to analyze treatment outcomes and prognostic markers, including immune and inflammatory factors, of postoperative radiation therapy (RT) administered to patients with cholangiocarcinoma (CCA). METHODS: We retrospectively included 59 patients with CCA who underwent surgery and postoperative RT with curative intent from 2004 to 2019. Patients received external irradiation (50 Gy in 25 fractions) using three-dimensional RT. We analyzed prognostic factors of inflammation, such as pre-RT platelet count, hemoglobin, lymphocyte count ratio (LCR) of the leukocyte count, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR). RESULTS: Tumor stages were distributed as follows: I (n = 8), II (n = 25), III (n = 15), and IVA (n = 11). The median follow-up was 24 months. Two-year overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and locoregional control (LRC) rates were 59.5%, 62.0%, 40.1%, and 66.7%, respectively. Univariate analysis revealed that lower LCR was significantly associated with shorter PFS (p = 0.0446). There was no significant difference between the median baseline values of PLR and NLR; and age ≥75, positive regional lymph node metastases (N+), and chemotherapy after RT were significantly associated with poor OS. Multivariate analysis revealed a significant association of N+ with worse OS, PFS, and CSS and that lower LCR was significantly associated with better PFS (p = 0.0234). Among late toxicity events, two patients (3.38%) were suspected with therapy-related liver toxicity. CONCLUSIONS: Lower LCR before RT was a better prognostic factor for postoperative RT of patients with CCA.

Outcomes of neoadjuvant gemcitabine plus S-1 and radiation therapy for borderline resectable pancreatic cancer.

BACKGROUND: The efficacy of multidisciplinary treatment, including neoadjuvant treatment, in borderline resectable pancreatic cancer (BRPC) remains unclear. We assessed the efficacy of neoadjuvant chemoradiotherapy with gemcitabine and tegafu/gimearcil/oteracil (S-1) for BRPC. METHODS: In a single center, nonrandomized prospective study, neoadjuvant chemoradiotherapy (NACRT) with gemcitabine plus S-1 was administered for BRPC (no. B090312028) in 122 patients enrolled between 2009 and 2015. Gemcitabine plus S-1 comprised gemcitabine on days 8 and 15, and daily S-1 on days 1-14. After two courses of gemcitabine plus S-1, 30 Gy radiotherapy was administered in 10 fractions with S-1. RESULTS: Eighty-four and 38 patients had BR-PV and BR-A, respectively. No deaths occurred during NACRT. Ninety-four patients (77%) underwent resection with curative intent. R0 resection was performed in 91% of resected cases. Patients who underwent post-NACRT resection had better overall survival than did patients without resection (mean survival time [MST]: 24.7 vs 9.6 months, 5-year-survival rate (5 years): 30.3% vs 0%, P < .001). Adjuvant chemotherapy was administered in 73% of patients. MST and 5-year survival rate of the patients treated with NACRT followed by resection and adjuvant chemotherapy were 29.6 months and 34.3%, respectively. CONCLUSIONS: Neoadjuvant chemoradiotherapy with gemcitabine and S-1 can be safely administered in BRPC and may require adjuvant chemotherapy. CLINICAL TRIAL REGISTRATION NUMBER: This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) UMIN000006782.

Proposal of nomograms to predict clinical outcomes in patients with ampulla of Vater cancer based on the Korea-Japan collaborative study.

BACKGROUND: In this study, we aimed to develop and validate a nomogram to predict overall survival (OS) and recurrence-free survival (RFS) in patients who underwent curative resection of ampulla of Vater (AOV) cancer. This is the first study for nomograms in AOV cancer patients using retrospective data based on an international multicenter study. METHODS: A total of 2007 patients with AOV adenocarcinoma who received operative therapy between 2002 January and 2015 December in Korea and Japan were retrospectively assessed to develop a prediction model. Nomograms for 5-year OS and 3-year RFS were constructed by dividing the patients who received and who did not receive adjuvant therapy after surgery, respectively. Significant risk factors were identified by univariate and multivariate Cox analyses. Performance assessment of the four prediction models was conducted by the Harrell's concordance index (C-index) and calibration curves using bootstrapping. RESULTS: A total of 2007 and 1873 patients were collected for nomogram construction to predict 5-year OS and 3-year RFS. We developed four types of nomograms, including models for 5-year OS and 3-year RFS in patients who did not receive postoperative adjuvant therapy, and 5-year OS and 3-year RFS in patients who received postoperative adjuvant therapy. The C-indices of these nomograms were 0.795 (95% confidence interval [CI]: 0.766-0.823), 0.712 (95% CI: 0.674-0.750), 0.804 (95% CI: 0.7778-0.829), and 0.703 (95% CI: 0.669-0.737), respectively. CONCLUSIONS: This predictive model could help clinicians to choose optimal treatment and precisely predict prognosis in AOV cancer patients.

Efficacy of neoadjuvant chemotherapy for initially resectable colorectal liver metastases: A retrospective cohort study.

BACKGROUND: The liver is the most common metastatic site of colorectal cancer. Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases (CRLMs). However, there are cases of early recurrence after upfront hepatectomy alone. In selected high-risk patients, neoadjuvant chemotherapy (NAC) may improve long-term survival. AIM: To determine the efficacy of NAC for initially resectable CRLMs. METHODS: Among 644 patients who underwent their first hepatectomy for CRLMs at our institution, 297 resectable cases were stratified into an upfront hepatectomy group (238 patients) and a NAC group (59 patients). Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression analysis. Propensity score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups, according to the number of poor prognostic factors. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Preoperative carcinoembryonic antigen levels (≥ 10 ng/mL) (P = 0.003), primary histological type (other than well/moderately differentiated) (P = 0.04), and primary lymph node metastases (≥ 1) (P = 0.04) were identified as independent poor prognostic factors for overall survival (OS) in the upfront hepatectomy group. High-risk status was defined as the presence of two or more risk factors. After propensity score matching, 50 patients were matched in each group. Among high-risk patients, the 5-year OS rate was significantly higher in the NAC group (13 patients) than in the upfront hepatectomy group (18 patients) (100% vs 34%; P = 0.02). CONCLUSION: NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.

Role of the Intramural Vascular Network of the Extrahepatic Bile Duct for the Blood Circulation in the Recipient Extrahepatic Bile Duct Used for Duct-to-Duct-Biliary-Anastomosis in Living Donor Liver Transplantation.

A duct-to-duct-biliary-anastomosis is the preferred biliary reconstruction technique in liver transplantation; biliary complications remain the major concerns for the technique. We examined the significance of the intramural vascular network of the extrahepatic bile duct (EBD) and its relevant vessels. We microscopically examined the axial sections of the EBD with 5 mm intervals of 10 formalin-fixed deceased livers. The luminal-areas of the 3 and 9 o'clock arteries correlated significantly and positively with the distance from the bifurcation of the right and left hepatic ducts (the 3 o'clock artery, r = 0.42, p < 0.001; the 9 o'clock artery, r = 0.39, p < 0.001); the ratios of the numbers of the intramural vessels to the areas of the corresponding sections of the EBD significantly correlated positively with the distance from the bifurcation of the right and left hepatic ducts (total vessels, r = 0.78, p < 0.001; arterioles, r = 0.52, p < 0.001; venules, r = 0.45, p < 0.001). This study demonstrated that there is a significant locoregional distributional heterogeneity of the intramural vessels among the EBD. The hepatic arteries neighboring the EBD primarily supply the blood flow to the EBD; thus, when the broader isolation of the EBD from the neighboring arteries is necessary, this locoregional distributional heterogeneity of the intramural vessels may render the EBD likely to suffer ischemia of the anastomotic site.

Surgical Indications for Huge Hepatocellular Carcinoma.

BACKGROUND/AIM: This study aimed to retrospectively analyse adverse predictors to identify patients with huge hepatocellular carcinoma who were not appropriate candidates for hepatic resection. PATIENTS AND METHODS: From 551 patients with hepatocellular carcinoma who underwent hepatectomy between 1992 and 2019, 92 were diagnosed with huge hepatocellular carcinoma (diameter >10 cm) and 115 were diagnosed with large hepatocellular carcinoma (diameter=5-10 cm). Clinical features and overall and disease-free survival rates were compared between the two groups. RESULTS: Cumulative overall survival was significantly worse in the huge group than in the large group (p=0.035). In the huge group, multivariate analyses revealed that liver cirrhosis, multiple intrahepatic metastases (≥4), poor histological grade, and macroscopic portal vein invasion were significantly associated with poor prognosis. CONCLUSION: We identified four adverse predictors of survival and determined that patients with two or more predictors are not appropriate candidates for straightforward hepatic resection.

CRMP4 Up-regulates M2 Macrophages and Myeloid-derived Suppressor Cells to Promote Pancreatic Cancer in Mice.

BACKGROUND/AIM: We previously observed higher prevalence of high-grade pancreatic intraepithelial neoplasia (PanIN) in LSL-KrasG12D/+; Pdx1Cre/+ (KC-Crmp4wild) mice than LSL-KrasG12D/+; Pdx1Cre/+; Crmp4-/- (KC-Crmp4-/-) mice. This study investigated the relationship between collapsin response mediator protein 4 (CRMP4) and immune cell infiltration in pancreatic cancer. MATERIALS AND METHODS: PanIN was induced by intraperitoneal injection of caerulein into KC-Crmp4wild and KC-Crmp4-/- mice, and immune cells in PanIN lesions were compared. Subcutaneous tumors were created by injecting Pan02 cells, and tumor diameter was compared between Crmp4wild and Crmp4-/- mice every 7 days. Peritumoral immune cells were examined immunohisto chemically. RESULTS: High-grade PanIN in KC mice showed statistically significantly high expression of CD163 (p=0.031) and CD11b (p=0.027). Following subcutaneous injection of Pan02 cells, tumor diameter was greater in Crmp4wild mice than Crmp4-/- mice. Crmp4wild mice exhibited higher CD163 and CD11b expression than Crmp4-/- mice in tumors (p<0.001). CONCLUSION: CRMP4 might promote pancreatic cancer by up-regulating M2 macrophages and myeloid-derived suppressor cells.

Survival Benefit of Primary Tumor Resection Among Elderly Patients with Pancreatic Neuroendocrine Tumors.

BACKGROUND: Pancreatectomy is the main curative therapeutic option for pancreatic neuroendocrine tumors (pNETs). Given the indolent behavior of pNETs and the relatively limited lifetime of elderly patients, the impact of primary site surgery (PSS) of pNETs on long-term outcomes among older patients has been a topic of debate. METHODS: Patients aged 70 or older with pNETs were identified in the Surveillance, Epidemiology and the End Results (SEER) database from 1998 to 2016. Propensity score matching was used to compare overall (OS) and cancer-specific survival (CSS) of patients who did versus did not undergo PSS. RESULTS: Among 2,319 elderly patients with pNETs, 942 patients (40.6%) underwent PSS, while 1,377 (59.4%) did not undergo PSS (non-PSS: NPSS). After propensity score matching (n = 433 in each group), PSS group had improved survival compared with the NPSS group (5-year OS: 53.4% vs. 37.3%; 5-year CSS: 77.2% vs. 58.1%, both p < 0.001). In contrast, subgroup analysis of individuals aged ≥ 80 revealed no difference in 5-year CSS (PSS: 69.2% vs. NPSS: 67.4%, p = 0.27). A subgroup analysis among patients who had small (≤ 2 cm) non-functional (NF) pNETs noted comparable long-term outcomes among patients who underwent PSS versus NPSS patients (5-year OS: 73.1% vs. 66.5%, p = 0.19; 5-year CSS: 98.5% vs. 95.2%, p = 0.14). CONCLUSIONS: Approximately 2 in 5 elderly patients with pNETs underwent PSS. While PSS was generally associated with prolonged OS and CSS among older patients, PSS was not associated with improved CSS among a subset of patients aged 80 or older, as well as among patients age ≥ 70 years with NF-pNET less than 2 cm.

Defining the Risk of Early Recurrence Following Curative-Intent Resection for Distal Cholangiocarcinoma.

BACKGROUND: Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgery for DCC. PATIENTS AND METHODS: Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop an ER risk score, and the predictive model was validated in an external dataset. RESULTS: Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1-2 points; 26.8%), or high (3-5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1-2 points); 32.7%, or high risk (3-5 points); 55.6% (p < 0.001)]. CONCLUSIONS: Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.

Significance of HMGA2 expression as independent poor prognostic marker in perihilar and distal cholangiocarcinoma resected with curative intent.

BACKGROUND: Extrahepatic cholangiocarcinoma requires invasive surgery and is associated with poor prognosis; thus, a prognostic biomarker is highly needed. Extrahepatic cholangiocarcinoma is sub-classified into two types based on their location, namely perihilar and distal. Perihilar cholangiocarcinoma requires lobectomy as curative surgical resection, whereas the distal requires pancreatoduodenectomy. HMGA2 overexpression is reported to correlate with progression, aggressiveness, dissemination and poor prognosis in several types of cancers. Although its association with extrahepatic cholangiocarcinoma has been reported, none of the previous studies assessed its significance in each subtype. METHODS: We assessed the expression of HMGA2 protein in surgical specimens after curative intent surgery in 80 patients including 41 with perihilar cholangiocarcinoma and 39 with distal cholangiocarcinoma by immunohistochemistry. We then examined its association with clinicopathological findings and patient survival outcomes. RESULTS: We found that HMGA2 was expressed in 51% (21 of 41) of perihilar cholangiocarcinoma and 41% (16 of 39) of distal cholangiocarcinoma samples. In perihilar cholangiocarcinoma, we found significant correlations between expression and vascular invasion and perineural invasion. In distal cholangiocarcinoma, we found that protein levels correlated with tumor grade. Univariate and multivariate analyses demonstrated that HMGA2 expression was an independent poor prognostic factor for patients with both subtypes of disease. CONCLUSIONS: Our results revealed that HMGA2 expression as an independent prognostic marker for both perihilar and distal cholangiocarcinoma that were resected with curative intent.

Defining and Predicting Early Recurrence after Resection for Gallbladder Cancer.

BACKGROUND: The optimal time interval to define early recurrence (ER) among patients who underwent resection of gallbladder cancer (GBC) is not well defined. We sought to develop and validate a novel GBC recurrence risk (GBRR) score to predict ER among patients undergoing resection for GBC. PATIENTS AND METHODS: Patients who underwent curative-intent resection for GBC between 2000 and 2018 were identified from the US Extrahepatic Biliary Malignancy Consortium database. A minimum p value approach in the log-rank test was used to define the optimal cutoff for ER. A risk stratification model was developed to predict ER based on relevant clinicopathological factors and was externally validated. RESULTS: Among 309 patients, 103 patients (33.3%) had a recurrence at a median follow-up period of 15.1 months. The optimal cutoff for ER was defined at 12 months (p = 3.04 × 10-18). On multivariable analysis, T3/T4 disease (HR: 2.80; 95% CI 1.58-5.11) and poor tumor differentiation (HR: 1.91; 95% CI 1.11-3.25) were associated with greater hazards of ER. The GBRR score was developed using ß-coefficients of variables in the final model, and patients were classified into three distinct groups relative to the risk for ER (12-month RFS; low risk: 88.4%, intermediate risk: 77.9%, high risk: 37.0%, p < 0.001). The external validation demonstrated good model generalizability with good calibration (n = 102: 12-month RFS; low risk: 94.2%, intermediate risk: 59.8%, high risk: 42.0%, p < 0.001). The GBRR score is available online at https://ktsahara.shinyapps.io/GBC_earlyrec/ . CONCLUSIONS: A novel online calculator was developed to help clinicians predict the probability of ER after curative-intent resection for GBC. The proposed web-based tool may help in the optimization of surveillance intervals and the counselling of patients about their prognosis.

Prophylactic drain management after pancreaticoduodenectomy without focusing on the drain fluid amylase level: A prospective validation study regarding criteria for early drain removal that do not include the drain fluid amylase level.

BACKGROUND/PURPOSE: Early drain removal (EDR) based on drain fluid amylase level (DFA) after pancreaticoduodenectomy excluded 15%-40% patients from EDR because of inappropriate DFA. METHODS: Of 198 pancreatoduodenectomy cases, we used the first 105 cases as an exploration cohort to construct the optimal criteria for EDR on postoperative day (POD)4 that were applied to the subsequent 93 cases used as the validation cohort. After that, we examined another 142 patients to further assess the efficacy of the new EDR criteria. RESULTS: Of the four independent predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) ([1] soft pancreas, [2] positive drain fluid culture on POD1, and [3] serum C-reactive protein [CRP] ≥13 mg/dL on POD4) in the exploration cohort, EDR was applied to cases in the validation cohort meeting the [2] and/or [3], enabling 96% (89/93) applicability of EDR. Outcomes were improved in the validation cohort compared to the exploration cohort; CR-POPF: 8.6% vs 25.7%, P = .005; Dindo-Clavien grade ≥ 3 complications: 23.7% vs 41.9%, P = .007; and median hospital stay (day): 21 vs 27, P = .005. The subsequent 142 patients showed 92% (131/142) applicability of EDR and 5.6% (8/142) incidence of CR-POPF. CONCLUSIONS: Our new criteria for EDR, without DFA, enabled ≥ 90% applicability of EDR and reduced CR-POPF.

A case of triple digestive tract reconstruction in chronic pancreatitis complicated with bile ductal stenosis, duodenal stenosis, and portal vein stenosis: a case report.

BACKGROUND: Although endoscopic interventions for chronic pancreatitis are highly developed, surgery for severe complicated cases such as the coexistence of bile duct, duodenum, and portal vein stenosis is a challenging issue for surgeons. In such instances, pancreaticoduodenectomy could lead to massive intraoperative bleeding due to severe collateral veins. A surgical drainage procedure, instead of pancreatic resection, may be a reasonable and safer option in such cases, but the literature on a surgical drainage technique to resolve all obstructions of the pancreatic duct, bile duct, and duodenum at once is limited. We devised a new surgical drainage method for such cases with consideration for a possible future second surgery for newly developed pancreatic cancer because chronic pancreatitis is a well-known high-risk factor for pancreatic cancer in the long term. Here, we report this surgical procedure. CASE PRESENTATION: A 55-year-old man was diagnosed with alcoholic chronic pancreatitis 15 years ago. Before surgery, he underwent regular endoscopic pancreatic stenting for pancreatic ductal stenosis for 3 years. Three months before surgery, his duodenal stenosis worsened, and he was referred to our department for surgery. Preoperative imaging revealed pancreatic and bile duct stenosis, duodenal stenosis, and portal vein stenosis. To avoid intraoperative bleeding caused by the development of collateral veins, we performed a triple drainage procedure: longitudinal pancreaticojejunostomy with coring-out of the pancreatic head, hepaticojejunostomy, and gastrojejunostomy. The patient did not develop postoperative complications, and he was discharged from the hospital on postoperative day 14. For 5 years after surgery, no abdominal pain or recurrent pancreatitis was observed. CONCLUSION: Our triple drainage procedure seems effective and minimally invasive for patients complicated with bile duct stenosis, duodenal stenosis, and portal vein stenosis.

Impact of intramuscular adipose tissue content on short- and long-term outcomes of hepatectomy for colorectal liver metastasis: a retrospective analysis.

BACKGROUND: Numerous reports regarding sarcopenia have focused on the quantity of skeletal muscle. In contrast, the impact of the quality of skeletal muscle has not been well investigated. METHODS: A retrospective analysis of 115 patients who underwent initial hepatectomy for colorectal liver metastasis between January 2009 and December 2016 in our hospital was performed. Intramuscular adipose tissue content (IMAC) was used to evaluate the quality of skeletal muscle by analysing computed tomography (CT) images at the level of the umbilicus. The impact of poor skeletal muscle quality on short-term and long-term outcomes after hepatectomy for colorectal liver metastasis was analysed. RESULTS: Patients were divided into two groups (high IMAC and normal IMAC) according to their IMAC values, and their backgrounds were compared. There were no significant differences in most factors between the two groups. However, both body mass index (P = 0.030) and the incidence of postoperative complications of Clavien-Dindo grade 3 or worse (P = 0.008) were significantly higher in the high-IMAC group. In multivariate analyses, an operative blood loss > 600 ml (P = 0.006) and high IMAC (P = 0.008) were associated with postoperative complications of Clavien-Dindo grade 3 or worse. Overall survival and recurrence-free survival were significantly lower (P < 0.001 and P = 0.045, respectively) in the high-IMAC group than in the normal IMAC group. In multivariate analyses for poor overall survival, high IMAC was associated with poor overall survival (P < 0.001). CONCLUSIONS: IMAC is a prognostic factor for poor short- and long-term outcomes in patients with colorectal liver metastasis.

Role of Conversion Surgery for Unresectable Pancreatic Cancer After Long-Term Chemotherapy.

BACKGROUND: Unresectable pancreatic cancer (UR-PC) has a poor prognosis. Although conversion surgery has been considered a promising strategy for improving prognosis in UR-PC, the clinical benefit offered to patients with UR-PC remains controversial. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PC. METHODS: We evaluated patients with UR-PC referred to our department for possible surgical resection between January 2008 and June 2017. Resectability was evaluated using multimodal imaging in patients who underwent chemotherapy for more than 6 months. Conversion surgery was performed only in patients who were judged eligible for R0 resection. RESULTS: In total, 90 patients were evaluated. Among them, only 22 (24.4%) could actually undergo conversion surgery, and the R0 resection rate was 72.7% (16/22). Although Evans grade ≥ IIB was noted in six patients (27.3%), none achieved complete response (CR). The median survival time was significantly longer among patients who underwent conversion surgery than in the unresected patients who underwent chemotherapy (21.3 months vs. 12.6 months; p < 0.001). Multivariate and Kaplan-Meier analyses revealed microvascular invasion to have a significant adverse effect on recurrence-free survival (RFS: 7 months vs. not reached, p = 0.004) and overall survival (OS: 21 months vs. 85 months, p = 0.047). CONCLUSIONS: After long-term chemotherapy, conversion surgery for UR-PC is associated with long-term survival. Microvascular invasion is predictive of poor prognosis in these patients; adjuvant protocols are therefore needed for patients with microvascular invasion.