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OBJECTIVE De novo aneurysms generally develop in healthy vessels after parent artery occlusion for large internal carotid artery (ICA) aneurysm, possibly owing to increased hemodynamic stress in the remaining vessels. In recent years, there has been a shift toward flow diverter stent treatment. However, there is a lack of direct evidence and data that prove this change in hemodynamic stress in healthy vessels after parent artery occlusion and flow diverter stent treatment. The authors compared hemodynamic stress in healthy-side vessels before and after parent artery occlusion and flow diverter treatments. METHODS The authors included patients who underwent 3D cine phase-contrast MRI before and after large ICA aneurysm treatment. Spatially and temporally averaged volume flow rates and spatially averaged systolic wall shear stress (WSS) in healthy-side ICA distal to the posterior communicating artery (C1 segment according to Fisher’s classification) were measured before and after parent artery occlusion and flow diverter treatments. RESULTS Seventeen patients were included (5 patients in the parent artery occlusion group and 12 in the flow diverter group). At 1–2 months after treatment, median volume flow rate in healthy-side ICA increased from 5.36 ml/sec to 6.28 ml/sec (total increase 117%, p = 0.04) in the parent artery occlusion group and from 4.65 ml/sec to 4.93 ml/sec (total increase 106%, p = 0.02) in the flow diverter group. In the parent artery occlusion group, median WSS in the C1 segment of the healthy-side ICA increased from 3.91 Pa to 5.61 Pa (total increase 143%, p = 0.08); however, no significant increase was observed in the flow diverter group (4.29 Pa to 4.57 Pa [total increase 107%, p = 0.21]). CONCLUSIONS Postoperatively, volume flow rate and WSS in the C1 segment of the healthy-side ICA significantly increased in the parent artery occlusion group. Therefore, the parent artery occlusion group was more prone to de novo aneurysm than the flow diverter group.

BACKGROUND Clinical tumor staging is essential information for making a therapeutic decision in cancer. This study aimed to identify the optimal tumor classification system for predicting resectability and survival probability in perihilar cholangiocarcinoma. METHODS Patients who were treated for perihilar cholangiocarcinoma between 2009 and 2018 were enrolled. Local tumor extension was staged radiologically according to a diameter-based classification system in addition to the AJCC, Blumgart, and Bismuth systems. Survival and resectability were compared between T subgroups, and the discriminability of the four systems was assessed with Harrell's concordance index (C-index). RESULTS Among 702 study patients, 559 (80.0%) underwent laparotomy, 489 (70.0%) of whom underwent resection. The resectability significantly decreased for more advanced tumors in all systems (P

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure.In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH).Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures.Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% (P = 0.432) and 24% versus 0% in advanced tumors (P = 0.011). Tumor size ≥18 mm (P = 0.041), portal vein invasion (P = 0.009), and conventional LH (P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years (P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group (P0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor (P = 0.009) along with ductal margin status (P = 0.030).The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.

OBJECTIVE To visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. BACKGROUND Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. METHODS Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. RESULTS A total of 4230 complications occurred in the 484 study patients (CDC grade I, n=27; II, n=132; IIIa, n=290; IIIb, n=4; IVa, n=21; IVb, n=1; and V, n=9). The trajectory was categorized into 3 patterns: mild (n=209), moderate (n=235), and severe (n=40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P

BACKGROUND The efficacy of adjuvant chemotherapy for biliary cancers remains controversial because of conflicting results from previous phase 3 studies that used different key drugs and enrolled patients with heterogeneous tumor sites and disease stages. Fluoropyrimidine seems more beneficial than gemcitabine (GEM) combination regimens in the adjuvant setting; however, data comparing the survival benefit between GEM- and fluoropyrimidine-based regimens are lacking. METHODS Patients who underwent resection for node-positive perihilar cholangiocarcinoma were included. The patients who underwent adjuvant chemotherapy were divided into the S-1 and GEM groups according to the regimen. The recurrence-free survival (RFS) and the overall survival (OS) were compared between the groups and adjusted with propensity scores generated from 14 potentially confounding clinicopathological factors. RESULTS In total, 186 patients (Surgery alone, n = 71; S-1, n = 60; GEM, n = 55) were included. The S-1 and GEM completion rates were 75% and 65%, respectively. Among the patients who underwent adjuvant therapy, the RFS was longer in the S-1 group patients than the GEM group patients (median, 24.4 months vs 14.9 months; P = .044) whereas the OS was not significantly different between the groups (median, 48.5 months vs 35.0 months; P = .324). After propensity score adjustment, the differences in RFS and OS between the groups were more evident (HR: 2.696, 95% CI: 1.739-4.180 P

Background: Nutritional status and tumor markers are important prognostic indicators for surgical decisions in pancreatic carcinoma. This study aimed to stratify the probability of surviving pancreatic carcinoma based on systematically chosen nonanatomic biomarkers. Methods: We included 187 consecutive patients that underwent surgical resections for pancreatic carcinoma. We performed multivariable analyses to evaluate prognostic indicators, including 4 blood-test indexes: the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index, and the modified Glasgow prognostic score; and 4 body-composition indexes: the normalized total psoas muscle area, the normalized total elector spine muscle area, the psoas muscle computed tomography value, and the elector spine muscle computed tomography value. Results: Poor survival was associated with 2 independent risk factors: neutrophil-to-lymphocyte ratio ≥3.0 (hazard ratio, 1.54) and prognostic nutritional index

Diagnosis and severity assessments of portosystemic shunts (PSSs) are important because the pathology sometimes results in severe hepatic encephalopathy, which can be treated almost completely by shunt embolization. At present, morphological assessment of PSS is performed mainly by computed tomography, and ultrasound is used for blood flow assessment. In two cases of PSS-related hepatic encephalopathy, we used time-resolved 3D cine phase-contrast (4D-flow) magnetic resonance imaging (MRI) to assess blood flow before and after shunt embolization. Before the intervention, blood flow in the main trunk of the superior mesenteric vein was mostly hepatofugal. However, post-interventional 4D-flow MRI revealed hepatopetal superior mesenteric vein flow with significantly increased portal vein blood flow. 4D-flow MRI is an ideal adjunct to Doppler ultrasonography, allowing for objective and visual assessment of morphology and blood flow of the portal venous system, including PSSs, and is useful in determining the indications for, and outcome of, PSS embolization.

We aimed to investigate the hypothesis that preoperative thickness of the abdominal cavity influenced on the gastrojejunostomy position and the incidence of delayed gastric emptying (DGE) after pancreatoduodenectomy.Between January 2009 and December 2018, consecutive patients who underwent subtotal stomach-preserving pancreatoduodenectomy were retrospectively reviewed. Thickness of the abdominal cavity at the level of the celiac axis (TACC) and umbilicus (TACU) were measured using computed tomography before surgery. The ventral deviation of the gastrojejunostomy was evaluated as the sagittal fundus anastomotic angle (SFAA) using sagittal computed tomography images taken after surgery.A total of 281 patients were included. Of these, clinically relevant DGE (CR-DGE) was observed in 47 patients. TACC was significantly correlated with SFAA (R = 0.53, P 0.001). Both TACC and SFAA were significantly greater in patients with CR-DGE compared to those without CR-DGE. In contrast, TACU was not associated with SFAA and the incidence of CR-DGE. Multivariate analysis revealed that TACC110 mm (odds ratio, 3.07; p = 0.002) and pancreatic fistula (odds ratio, 2.71; p = 0.013) were identified as independent risk factors for CR-DGE.Thickness of the upper abdominal cavity had a significant influence on gastrojejunal anatomic position and the development of CR-DGE after pancreatoduodenectomy.

The indications for neoadjuvant chemotherapy (NAC) in resectable colorectal liver metastases (CRLMs) remain unclear. Tumor burden score (TBS) is a prognostic tool based on tumor size and number of tumors. However, its utility in the NAC setting for initially resectable CRLM has never been investigated. TBS is a distance from the origin on a Cartesian plane to the coordinates (x, y) = (tumor size in centimeter, number of tumors). TBS

The aim of this study was to conduct a flow experiment using a cerebrovascular phantom and investigate whether magnetic resonance angiography (MRA) could replace three-dimensional rotational angiography (RA) and computed tomography angiography (CTA) to construct vascular models for computational fluid dynamics (CFD). We performed MRA and 3D cine phase-contrast (PC) MR imaging with a silicone cerebrovascular phantom of an internal carotid artery-posterior communicating artery aneurysm with blood-mimicking fluid, and controlled flow with a flowmeter. We also obtained RA and CTA data for the phantom. Four analysts constructed vascular models based on the three different modalities. These 12 constructed models used flow information based on 3D cine PC MR imaging for CFD. We compared RA-, CTA-, MRA-based CFD results using the micro-CT-based CFD result as the criterion standard to investigate whether MRA-based CFD was not inferior to RA- or CTA-based CFD. We also analyzed the inter-analyst variability. Wall shear stress (WSS) distributions and streamlines of RA- or MRA-based CFD and those of micro-CT-based CFD were similar, but the vascular models and WSS values were different. Accuracy in measurements of blood vessel diameter, cross-sectional maximum velocity, and spatially averaged WSS was the highest for RA-based CFD, followed by MRA-based and CTA-based CFD using micro-CT-based CFD result as the reference. Except maximum velocity from CTA, all other parameters had good inter-analyst agreement using different modalities. The results demonstrated that non-invasive MRA can be used for cerebrovascular CFD models with good inter-analyst agreements.

Although bile duct resection (BDR) in addition to pancreaticoduodenectomy (PD) is considered a surgical approach in patients with middle-third cholangiocarcinoma (MCC), available prognostic information after BDR remains very limited. The aim of this study was to reappraise BDR from the viewpoint of surgical oncology. Patients who underwent BDR or PD for MCC between 2001 and 2010 at 32 Japanese hospitals were included. Clinicopathological factors were retrospectively compared according to surgical procedure to identify a subset cohort who benefited most from BDR. During the study, 92 patients underwent BDR (n = 38) or PD (n = 54). BDR was characterized by a shorter operation time, less blood loss, less frequent complications, and lower mortality, than PD. The incidence of positive surgical margins was 26.3% versus 5.6% (P = 0.007). The survival rate after BDR was significantly worse than that after PD: 38.8% versus 54.8% at 5 years (P = 0.035), and BDR was independently associated with deteriorated survival [hazard ratio (HR), 1.76; P = 0.023] by multivariable analysis. In the BDR group, tumor length

In “anatomic” right hepatic trisectionectomy for advanced perihilar cholangiocarcinoma, the left hepatic duct is divided at the left side of the umbilical portion (UP) of the left portal vein (LPV). For this reason, the left hepatic duct is completely detached from the UP after all division of the portal branches arising cranially from the UP. However, little is known about these thin portal branches. Using 3D imaging processing software, we examined the portal branches arising cranially from the UP of the LPV in 100 patients who underwent multidetector row computed tomography (MDCT). Special attention was paid to the portal branch running to the left lateral sector, designated as the left cranio-lateral branch. The left cranio-lateral portal branch number was 0 in 57 patients, 1 in 32 patients, and 2 in 11 patients. Thus, 54 left cranio-lateral branches were identified, arising from near the cul-de-sac of the UP, from near the elbow of the LPV, or from the UP trunk. The median volume of the territory supplied by the left cranio-lateral portal branch was 21 mL (range, 5–47 mL), and the median ratio to the left lateral sector was 11.8% (range, 1.7–25.0%). Approximately 40% of patients had the left cranio-lateral portal branches arising cranially from the UP and running to the left lateral sector. When planning anatomic right hepatic trisectionectomy, the presence or absence of this branch should be checked by using 3D imaging with MDCT.

To date, five randomized controlled trials have assessed the clinical benefit of perioperative steroid administration in hepatectomy; however, all of these studies involved a substantial number of ‘minor’ hepatectomies. The benefit of steroid administration for patients undergoing ‘complex’ hepatectomy, such as major hepatectomy with extrahepatic bile duct resection, is still unclear. This study aimed to evaluate the clinical benefit of perioperative steroid administration for complex major hepatectomy. Patients with suspected hilar malignancy scheduled to undergo major hepatectomy with extrahepatic bile duct resection were randomized into either the control or steroid groups. The steroid group received hydrocortisone 500 mg immediately before hepatic pedicle clamping, followed by hydrocortisone 300 mg on postoperative day (POD) 1, 200 mg on POD 2, and 100 mg on POD 3. The control group received only physiologic saline. The primary endpoint was the incidence of postoperative liver failure. A total of 94 patients were randomized to either the control (n = 46) or steroid (n = 48) groups. The two groups had similar baseline characteristics; however, there were no significant differences between the groups in the incidence of grade B/C postoperative liver failure (control group, n = 8, 17%; steroid group, n = 4, 8%; p = 0.188) and other complications. Serum bilirubin levels on PODs 2 and 3 were significantly lower in the steroid group than those in the control group; however, these median values were within normal limits in both groups. Perioperative steroid administration did not reduce the risk of postoperative complications, including liver failure following major hepatectomy with extrahepatic bile duct resection.

Hilar cholangiocarcinoma is a highly intractable malignancy. One of the reasons for its intractability is that most patients with the disease are diagnosed with an advanced stage of the disease at their initial presentation. Surgical resection is the standard therapy for hilar cholangiocarcinoma, providing a chance for a cure, and an aggressive surgical approach substantially increases the number of resectable tumors that are initially regarded as unresectable tumors. The success and standardization of the aggressive approach is warranted by meticulous preoperative management that prevents fatal postoperative complications. Extended resection procedures, including hepatic trisectionectomy for Bismuth type IV tumors, hepatopancreaticoduodenectomy for tumors with extensive longitudinal tumor spreading, and combined vascular resection with reconstruction for tumors with the involvement of hepatic vascular structures, have been challenged to expand the surgical indication. Due to acceptable surgical/survival outcomes, the three extended procedures are currently regarded as extended but standard options in specialized hepatobiliary centers. Although it remains a controversial multidisciplinary approach, the combination of these extended procedures with an adjuvant/neoadjuvant treatment is a promising approach for further improving the resectability of tumors and the survival of patients.

Nodal metastasis is a leading attributable factor of poor survival in biliary tract cancer (BTC), and adjuvant chemotherapy targeting this high-risk feature has not been attempted to date. This study aimed to test the efficacy of adjuvant S − 1 for patients with node-positive BTC. This single-arm multicenter phase 2 trial enrolled patients who underwent resection for histologically proven node-positive BTC. In this trial, S − 1 was administered at a dose of 80–120 mg/day on 14 days of a tri-weekly cycle for 6 months. The primary end point of the trial was 3-year overall survival (OS), in which the result would be promising if the 90% confidence interval (CI) surpassed a threshold of 30% (alpha error, 0.1; beta error, 0.2). The secondary end points were relapse-free survival (RFS), feasibility, and toxicity. The trial included 50 patients with perihilar (n = 23) or distal (n = 20) cholangiocarcinoma, or gallbladder cancer (n = 7). The median numbers of positive lymph nodes and examined lymph nodes were respectively 2 and 15. The 3-year OS and RFS were respectively 50% (90% CI, 40.9–59.1%) and 32.0% (95% CI, 19.1–44.9%), with median survival times of 34.6 months (95% CI, 19.3–49.8 months) and 18.4 months (95% CI, 11.9–24.9 months). Although hematologic toxicity often occurred, grades 3 and 4 toxicity were rare. The completion rate of the test therapy was 64%, and the median relative dose intensity was 87.5% (interquartile range, 50–100%). Adjuvant chemotherapy with S − 1 may be promising for patients with node-positive BTC.

BACKGROUND Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

Background In situ cholangiocarcinoma is difficult to detect by imaging studies. Thus, cholangiocarcinoma is rarely resected with a preoperative definitive diagnosis, especially nonpapillary flat type in situ carcinoma, which is extremely rare. Case presentation A 70-year old man was diagnosed with gallbladder cancer and received open cholecystectomy with lymphadenectomy at a local hospital. Histologically, the tumor was localized in the mucosal layer, and no lymph node metastases were found. Three months later, hilar bile duct stricture due to delayed bile duct ischemia was found. Then, biliary drainage was performed with endoscopic biliary stenting. Three months later, the patient experienced cholangitis with septic shock, and percutaneous transhepatic biliary drainage (PTBD) into the left intrahepatic bile duct was performed. Unexpectedly, the aspiration bile cytology of the PTBD catheter showed malignant cells, and the patient was referred to our clinic for possible surgical treatment. According to additional studies, the hilar bile duct stricture was 3 cm in length. None of the imaging studies detected malignant cells in the bile duct around the hilar stricture. The left portal vein was obstructed due to inadvertent puncture of the PTBD. No findings indicated cholangiocarcinoma. We performed left hepatectomy with caudate lobectomy and extrahepatic bile duct resection. The postoperative course was uneventful. In the final pathology, flat type in situ carcinoma was found at the confluence of the right and left hepatic ducts, which was distant from the biliary stricture. Conclusions When a tumor is undetectable but cytology is positive, in situ cholangiocarcinoma may exist; thus, surgery should be carefully considered.

The border between segments VI and VII of the right posterior sector of the liver is controversial owing to lack of anatomical landmarks. This study aimed to examine the segmentation of the right posterior sector. Using three-dimensional software, ramification type of the right posterior portal vein (RPPV) was analysed in 100 patients. A bow-shaped anatomy, in which the RPPV exhibits a downward convex bow shape with several ramifications, was found in 50 patients. A bifurcation anatomy, in which the RPPV bifurcates into the cranial and caudal branches, was observed in 45 patients. In the bow-shaped anatomy, setting the segmentation was difficult due to lack of definite landmarks; thus, the downward portal branches were determined as segment VI branches, while horizontal and upward branches were determined as segment VII branches. In the bow-shaped anatomy, the incidence of full exposure of a thick branch of the right hepatic vein on virtual transection surface was 60.0%, while in the bifurcation anatomy, it was only 11.1%. No relations were observed between RPPV anatomy and main PV/right hepatic vein anatomy. The volumes of segments VI and VII were equal in both the bow-shaped and bifurcation anatomy. The bow-shaped and bifurcation types are commonly observed in RPPV anatomy. In the bifurcation anatomy, the right posterior sector is divided into segments VI and VII. In the bow-shaped anatomy, setting the segmentation was difficult, thus it may be compelled to be arbitrarily determined.

Background Traditional classifications for open liver resection are not always associated with surgical complexity and postoperative morbidity. The aim of this study was to test whether a three-level classification for stratifying surgical complexity based on surgical and postoperative outcomes, originally devised for laparoscopic liver resection, is superior to classifications based on a previously reported survey for stratifying surgical complexity of open liver resections, minor/major nomenclature or number of resected segments. Methods Patients undergoing a first open liver resection without simultaneous procedures at MD Anderson Cancer Center (Houston cohort) or the University of Tokyo (Tokyo cohort) were studied. Surgical and postoperative outcomes were compared among three grades: I (wedge resection for anterolateral or posterosuperior segment and left lateral sectionectomy); II (anterolateral segmentectomy and left hepatectomy); III (posterosuperior segmentectomy, right posterior sectionectomy, right hepatectomy, central hepatectomy and extended left/right hepatectomy). Results In both the Houston (1878 patients) and Tokyo (1202) cohorts, duration of operation, estimated blood loss and comprehensive complication index score differed between the three grades (all P < 0·050) and increased in stepwise fashion from grades I to III (all P < 0·001). Left hepatectomy was associated with better surgical and postoperative outcomes than right hepatectomy, extended right hepatectomy and right posterior sectionectomy, although these four procedures were categorized as being of medium complexity in the survey-based classification. Surgical outcomes of minor open liver resections also differed between the three grades (all P < 0·050). For duration of operation and blood loss, the area under the curve was higher for the three-level classification than for the minor/major or segment-based classification. Conclusion The three-level classification may be useful in studies analysing open liver resection at Western and Eastern centres.

This study investigated the correlation between the fecal profile and muscle mass, which has not been elucidated before. This study included patients who underwent hepatectomy, pancreatoduodenectomy, or esophagectomy and had fecal samples collected preoperatively and mesenteric lymph nodes (MLNs) harvested intraoperatively to determine the fecal profile and presence of bacteria in the MLNs. Total psoas area (TPA) was measured at the third lumbar vertebra using preoperative computed tomography images. TPA was standardized by body surface area (BSA) using the following equation: standardized TPA (mm2/m2) (stTPA) = TPA (mm2)/BSA (m2). The fecal concentrations of representative microorganisms and organic acids also were measured. A total of 127 patients undergoing hepatectomy (n = 48), pancreatoduodenectomy (n = 44), and esophagectomy (n = 35) were included. The fecal levels of predominant obligate anaerobes showed a positive correlation with stTPA, whereas that of pathogenic microorganisms showed a negative correlation with stTPA. The fecal concentrations of total short chain fatty acids (the sum of acetic acid, propionic acid, and butyric acid) also showed a positive correlation with stTPA. The stTPA was significantly lower in patients with positive microorganisms in the MLNs (patients with bacterial translocation) compared to those without microorganisms in the MLNs (p = 0.047). This study was the first to demonstrate the association between muscle mass and the fecal profile, as well as their association with bacterial translocation.

Background This study sought to investigate the utility of constant negative pressure for external drainage of the main pancreatic duct in preventing postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. Methods Only patients with soft pancreas were included. In the former period (July 2013 to May 2015), gravity dependent drainage was applied (gravity dependent drainage group), and in the latter period (June 2015 to November 2016), constant negative pressure drainage (negative pressure drainage group) was applied to the main pancreatic duct stent. Results There were 37 patients in the gravity dependent drainage group and 39 patients in the negative pressure drainage group. Clinically relevant POPF occurred in 21 patients (56.8%) in the gravity dependent drainage group and 13 patients (33.3%) in the negative pressure drainage group (p = 0.040). The incidence rate of major complications (Clavien-Dindo grade > III) was significantly lower in the negative pressure drainage group (13.2%) compared to the gravity dependent drainage group (48.7%) (p = 0.001). In-hospital stay was also significantly shorter in the negative pressure drainage group compared to the gravity dependent drainage group (median 25 vs. 33 days, p = 0.024). Multivariate analysis demonstrated that the gravity dependent drainage was one of the independent risk factors for the incidence of POPF (odds ratio, 3.33; p = 0.032). Conclusions In patients with soft pancreas, the incidence rate of clinically relevant POPF may be reduced by applying constant negative pressure to the pancreatic duct stent. It also has a potential to reduce overall incidence of major complications and shorten in-hospital stay after pancreatoduodenectomy.

Background Only 3 case reports have addressed pleural dissemination in association with percutaneous transhepatic biliary drainage. The aim of this study was to investigate recurrence after resection of cholangiocarcinoma after percutaneous transhepatic biliary drainage and to clarify the incidence of and the factors responsible for pleural dissemination. Methods Between 2001 and 2015, we reviewed retrospectively all consecutive patients who underwent resection for perihilar or distal cholangiocarcinoma after percutaneous transhepatic biliary drainage for recurrence, including pleural dissemination. Results During the study period, all consecutive patients underwent resection of cholangiocarcinoma after management with percutaneous transhepatic biliary drainage. Of these, 100 patients (32.1%) underwent left-sided percutaneous transhepatic biliary drainage alone, and 212 (67.9%) underwent right-sided percutaneous transhepatic biliary drainage with or without left-sided percutaneous transhepatic biliary drainage. Pleural dissemination, which developed exclusively on the right side of the thoracic cavity after resection, was found in 12 patients (3.8%); these patients underwent right-sided percutaneous transhepatic biliary drainage; computed tomography demonstrated that the percutaneous transhepatic biliary drainage catheter passed through the thoracic cavity in all 12 patients. The diagnosis of pleural dissemination was made at a median of 381 days (range, 44 to 2,944 days) after operation. Survival was poor, with a median survival time of 516 days. Statistically, right-sided percutaneous transhepatic biliary drainage was identified as a risk factor for pleural dissemination. Conclusion Pleural dissemination after right-sided percutaneous transhepatic biliary drainage is likely a procedure-related iatrogenic complication because of the “special route” by which the percutaneous transhepatic biliary drainage catheter must be passed through the right thoracic cavity.

Background Little is known about the effect of additional resection for a frozen-section-positive distal bile duct margin (DM) in perihilar cholangiocarcinoma. Methods Patients who underwent surgical resection for perihilar cholangiocarcinoma between 2001 and 2015 were analysed retrospectively, focusing on the DM. Results Of 558 consecutive patients who underwent frozen-section examination for a DM, 74 (13·3 per cent) had a frozen-section-positive DM with invasive cancer or carcinoma in situ. Eventually, 53 patients underwent additional resection (bile duct resection in 44 and pancreatoduodenectomy in 9), whereas the remaining 21 patients did not. Ultimately, R0 resection was achieved in 30 of the 53 patients (57 per cent). No patient who underwent additional resection died from surgical complications. The 44 patients with additional bile duct resection had a 5-year overall survival rate of 31 per cent. Overall survival of the nine patients who had pancreatoduodenectomy was better, with a 10-year rate of 67 per cent. Survival of the 21 patients without additional resection was dismal: all died within 5 years. Multivariable analyses identified nodal status and additional resection as independent prognostic factors (lymph node metastasis: hazard ratio (HR) 2·26, 95 per cent c.i. 1·26 to 4·07; bile duct resection versus no additional resection: HR 0·32, 0·17 to 0·60; pancreatoduodenectomy versus no additional resection: HR 0·08, 0·02 to 0·29). Conclusion Additional resection for frozen-section-positive DM in perihilar cholangiocarcinoma frequently yields R0 margins. It offers a better chance of long-term survival, and thus should be performed in carefully selected patients.

Background Intraductal papillary neoplasm of the bile-duct (IPNB) has recently been further subclassified into “so-called IPNBs” (Type-1) and “narrow-sense papillary cholangiocarcinomas” (Type-2), but their differential diagnosis is challenging. This study aimed to reevaluate Type-1 and Type-2 IPNBs. Methods Consecutive patients who underwent papillary bile-duct tumor resection were included. Using six pathological features (location, mucin secretion, histological architecture, histological type, presence of a low/intermediate-dysplasia component, and proportion of the invasive component), all papillary tumors were scored. Tumors scoring 5–6 were classified as Type-1, 0–1 as Type-2, and 2–4 as Type-Unclassifiable. Results The 181 papillary bile-duct tumor patients were divided into three groups, consisting of 12 Type-1, 46 Type-2, and 123 Type-Unclassifiable—gray-zone lesions between Type-1 and Type-2 that constituted the largest proportion of papillary tumors. Type-1 tumors were pathologically the least advanced, while the other types showed gradual advancement. The 5-year survival rate was better for patients with Type-1 tumors than for those with Type-Unclassifiable or Type-2 tumors. Conclusion The scoring system worked well to delineate a continuous spectrum of pathologic features ranging from Type-1, through Type-Unclassifiable, to Type-2, the latter two being challenging to differentially diagnose. Type-1 is regarded as an early neoplasm of Type-Unclassifiable and Type-2.

OBJECTIVE To evaluate the efficacy and safety of combined vascular resection (VR) in advanced perihilar cholangiocarcinoma (PHC). SUMMARY OF BACKGROUND DATA Hepatectomy combined with portal vein resection (PVR) and/or hepatic artery resection (HAR) is technically demanding but an option only for tumor eradication against PHC involving the hilar hepatic inflow vessels; however, its efficacy and safety have not been well evaluated. METHODS Patients diagnosed with PHC during 2001-2018 were included. Patients who underwent resection were divided according to combined VR. Patients undergoing VR were subdivided according to type of VR. Postoperative outcomes and OS were compared between patient groups. RESULTS Among the 1055 consecutive patients, 787 (75%) underwent resection (without VR: n = 484, PVR: n = 157, HAR: n = 146). The incidences of postoperative complications and mortality were 49% (without VR vs with VR, 48% vs 50%; P= 0.715) and 2.1% (without VR vs with VR, 1.2% vs 3.6%; P= 0.040), respectively. The OS of patients who underwent resection with VR (median, 30 months) was shorter than that of those who underwent resection without VR (median, 61 months; P < 0.0001); however, it was longer than that of those who did not undergo resection (median, 10 months; P < 0.0001). OS was not significantly different between those who underwent PVR and those who underwent HAR (median, 29 months vs 34 months; P = 0.517). CONCLUSION VR salvages a large number of patients from having locally advanced PHC that is otherwise unresectable and is recommended if the hilar hepatic inflow vessels are reconstructable, providing acceptable surgical outcomes and substantial survival benefits.

Objective To evaluate the impact of complications on long-term survival in patients with perihilar cholangiocarcinoma. Background Surgical resection for perihilar cholangiocarcinoma is vulnerable to postoperative complications. The prognostic impact of complications in patients with this disease is unknown. Methods The medical records of patients who underwent curative-intent hepatectomy for perihilar cholangiocarcinoma between 2010 and 2017 were reviewed retrospectively. The comprehensive complication index (CCI) was calculated based on all postoperative complications, which were graded by the Clavien-Dindo classification (CDC). Patients were divided into high and low CCI groups by the median score, and survival was compared between the two groups. Results Excluding 8 patients who died in hospital, 369 patients were analyzed. The CDC grade was I in 20 (5.4%), II in 108 (29.3%), III in 224 (60.7%), and IV in 17 (4.6%) patients. The CCI increased with increasing CDC grade; the median was 42.9 (range, 15.0-98.9). Overall survival (OS) differed significantly between the high (n = 187) and low (n = 182) CCI groups (41.2% versus 47.9% at 5 years; p = 0.041). However, multivariable analyses demonstrated that traditional clinicopathological factors were independent predictors of survival and that the dichotomized CCI was not. In addition, the CCI score as a continuous variable was not an independent prognostic factor for OS in the multivariable analyses (hazard ratio per 1 CCI score: 1.00, 95% confidence interval: 0.99-1.01, p = 0.775). Conclusion Cumulative postoperative complications after resection of perihilar cholangiocarcinoma only moderately deteriorate long-term survival, and should not be an argument to deny surgery in this high risk population.

We present a case of a patient who underwent portal vein (PV) stenting for PV stenosis after a living-donor liver transplantation. A pretreatment 3D cine phase-contrast (4D-flow) MRI showed decreased, though hepatopetal, blood flow in the PV. After stenting, 4D-flow MRI confirmed an improvement in PV flow, with a more homogeneous flow distribution to each hepatic segment. 4D-flow MRI are valuable for understanding the hemodynamics of this area, planning for treatments, and evaluating the outcome of the interventions.

This study focused on the Kuchikara Taberu Balance Chart (KTBC) as a tool for swallowing function evaluation. To clarify the relationship between videoendoscopic (VE) examination of swallowing function and the KTBC, we compared median KTBC scores with and without laryngeal penetration identified by VE. Sixty-five patients with a mean age of 84.3 ± 7.9 years were examined at the Towada City Hospital. The patients were classified into groups based on laryngeal penetration, including 28 patients with and 37 patients without penetration. We found no significant differences in patient backgrounds. The median KTBC score (interquartile range) was 36.5 (31–44.5) in the group with laryngeal penetration and 42 (35–48.5) in the group without penetration, but the scores were not significantly different (level of statistical significance at α = 0.0036 determined by the Bonferroni correction method) when compared with the Mann–Whitney U test (36.5 vs. 42, z = -2.33, p = 0.020). The median respiratory condition (3 vs. 4, z = − 3.23; p

Background The indications for major hepatectomy for gallbladder cancer either with or without pancreatoduodenectomy remain controversial. The clinical value of these extended procedures was evaluated in this study. Methods Patients who underwent major hepatectomy for gallbladder cancer between 1996 and 2016 were identified from a prospectively compiled database. Postoperative outcomes and overall survival were compared between patients undergoing major hepatectomy alone or combined with pancreatoduodenectomy (HPD). Results Seventy-nine patients underwent major hepatectomy alone and 38 patients had HPD. The patients who underwent HPD were more likely to have T4 disease (P < 0·001), nodal metastasis (P = 0·015) and periaortic nodal metastasis (P = 0·006), but were less likely to receive adjuvant therapy (P = 0·006). HPD was associated with a high incidence of grade III or higher complications (P = 0·002) and death (P = 0·037). Overall survival was longer in patients who underwent major hepatectomy alone than in patients who underwent HPD (median survival time 32 versus 10 months; P < 0·001). In multivariable analysis, surgery in the early period (1996–2006) (P = 0·002), pathological T4 disease (P = 0·005) and distant metastasis (P < 0·001) were associated with shorter overall survival, and cystic duct tumour (P = 0·002) with longer overall survival. Conclusion Major hepatectomy alone for gallbladder cancer contributes to favourable overall survival with low morbidity and mortality, whereas HPD is associated with poor overall survival and high morbidity and mortality rates. HPD may eradicate locally spreading gallbladder cancer; however, the indication for the procedure is questioned from an oncological viewpoint.

Background The survival impact of specific body composition changes during preoperative chemotherapy in patients with colorectal liver metastases undergoing curative-intent surgery remains unclear. This study aimed to determine the impact of changes in body weight and muscle mass during preoperative chemotherapy on survival after hepatectomy in patients with colorectal liver metastases. Methods Consecutive patients with colorectal liver metastases undergoing preoperative chemotherapy and curative hepatectomy during 2009–2013 were retrospectively analyzed. Recurrence-free and overall survival were examined according to body compositions, including muscle mass, as measured by skeletal muscle index (area of muscle [cm2]/square of height [m2]), and body weight before and after preoperative chemotherapy. Results The median follow-up duration in overall 169 patients was 47 months. Skeletal muscle index and body weight changed significantly during chemotherapy (skeletal muscle index: –0.52 cm2/m2, P = .03; body weight: +1.1 kg, P = .002). Patients with major muscle mass loss (≥7%) had significantly shorter median RFS than patients with no or minor muscle mass loss ( Conclusion Major loss of muscle mass but not body weight loss during preoperative chemotherapy is significantly associated with poor recurrence-free survival after hepatectomy in patients with colorectal liver metastases. The mechanisms mediating this association may inform future trials on maintaining muscle mass with dedicated nutrition and exercise programs to improve outcomes.

This study sought to identify any significant predictors of blood loss during pancreatoduodenectomy (PD) among preoperative variables, including the body composition indexes. The preoperative data of patients undergoing PD were retrospectively reviewed. The objective variable was the percentage of blood loss during PD to the estimated circulating blood volume (proportional blood loss: PBL). The circulating blood volume was estimated using Nadler’s formula. The total psoas area, average Hounsfield units of psoas area (psoas muscle density: PMD), and visceral to subcutaneous adipose tissue area ratio (VSR) were measured at the third vertebra using preoperative plain computed tomography images. A univariate analysis and multiple linear regression analysis for PBL were conducted using the preoperative variables. A total of 415 patients were analyzed. The median PBL was 24.5%. The PMD (coefficient − 0.267; 95% CI − 0.518, − 0.015), VSR (coefficient 2.719; 95% CI 0.238, 5.201), serum albumin level (coefficient − 8.458; 95% CI − 13.02, − 3.898), neoadjuvant therapy (coefficient 9.605; 95% CI 1.722, 17.49), and prothrombin time-international normalized ratio (PT-INR, coefficient 38.63; 95% CI 10.94, 66.31) were independently associated with PBL. The preoperative PMD, VSR, serum albumin level, neoadjuvant therapy, and PT-INR independently affected PBL. These factors could therefore be potential targets to reduce blood loss during PD.

In the clinical setting, mild bacteremia cannot be detected by conventional culture methods, only by a highly sensitive bacterial detection system. One of the major causes of mild bacteremia is bacterial translocation (BT) induced by a dysregulated intestinal microenvironment and increased intestinal epithelial permeability. This condition is called "occult-bacterial translocation (O-BT)"; however, the concept of O-BT is not yet fully recognized. In our previous studies, done using a highly sensitive bacterial detection system such as bacterium-specific ribosomal RNA-targeted reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), O-BT was commonly observed in patients who underwent highly invasive surgery. We collected blood and mesenteric lymph node (MLN) samples from patients undergoing esophagectomy for esophageal cancer, before and after they were subjected to surgical stress. The detection rate of bacteria in these samples increased from approximately 20% before surgical stress to more than 50% after surgical stress. Moreover, positivity for bacteria in the blood or MLN samples was associated with the incidence of postoperative infectious complications (POICs). Using the RT-qPCR system, it is possible to detect the specific bacteria that cause O-BT immediately after surgery. This may allow us to select the exact antibiotic that targets possible pathogenic bacteria of POICs.

Background The T system for distal cholangiocarcinoma has been revised from a layer-based to a depth-based approach in the current American Joint Committee on Cancer (AJCC) classification. In perihilar cholangiocarcinoma, tumour depth in the staging scheme has not yet been addressed. The aim of this study was to propose a new T system using measured tumour depth in perihilar cholangiocarcinoma. Methods Patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2001 and 2014 were reviewed retrospectively. The vertical distance between the top of the tumour and deepest invasive cells was measured as invasive tumour thickness (ITT) by two independent pathologists. Log rank statistics were used to determine cut-off points, and the concordance (C) index was used to assess survival discrimination of each T system. Results ITT was measurable in all 440 patients, with a median value of 6·0 (range 0–45) mm. The median difference in ITT between observers was 0·6 (range 0–20) mm. Cut-off points for prognosis were 1, 5 and 8 mm. Five-year survival decreased with increasing ITT (P < 0·001): 67 per cent for ITT less than 1 mm (25 patients), 54·9 per cent for ITT 1 mm and over to less than 5 mm (138 patients), 43·4 per cent for ITT 5 mm and over to less than 8 mm (118 patients), and 32·2 per cent for ITT 8 mm and over (159 patients). The C-index of this classification was comparable to that of the current AJCC T classification (0·598 versus 0·589). Conclusion ITT is a reliable approach for making a depth assessment in perihilar cholangiocarcinoma. A four-tier ITT classification with cut-off points of 1, 5 and 8 mm is an adequate alternative to the current layer-based T classification.

Introduction Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway and SMAD4 gene mutations are thought to play a critical role in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for colorectal liver metastases (CLM). Methods Between 2005 and 2015, all patients with known SMAD4 mutation status who underwent resection of CLM were identified. Patients with SMAD4 mutation were compared to those with SMAD4 wild type. Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone. Results Of 278 patients, 37 (13%) were SMAD4 mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse in SMAD4-mutant patients compared to SMAD4 wild type (OS rate at 3 years, 62% vs. 82%; P Conclusion SMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM.

Background Circumportal pancreas (CP) is an anatomical anomaly in the form of abnormal parenchymal fusion between the uncinate process and the pancreatic body, and it requires an additional parenchymal dissection during pancreaticoduodenectomy (PD). This study aimed to investigate the prevalence of CP in PD and to evaluate the incidence of postoperative pancreatic fistula (POPF) among CP patients. Methods Patients who underwent PD from 2002 to 2012 (n = 552) were included. Operative records and preoperative images were independently reviewed to identify the presence of CP. The incidence of POPF was compared between CP and non-CP patients and was evaluated via multivariate analysis. Results CP was confirmed from operative records in 7 (1.3%) patients, and abnormal parenchymal fusion was identified from preoperative images in 8 (1.4%) patients. The incidence of POPF was significantly higher in CP patients than in non-CP patients (71% vs 32%, P = 0.039). On multivariate analysis, CP was an independent predictive factor for POPF (odds ratio, 9.97; 95% confidence interval, 1.76–56.6; P = 0.009). Discussion Surgeons should heed the presence of CP in PD because this rare anomaly requires an additional parenchymal dissection and may increase the incidence of POPF.

Background The aim of this study was to review the surgical outcomes of patients who underwent major hepatectomy with extrahepatic bile duct resection after preoperative biliary drainage with a particular focus on the impact of preoperative biliary colonization/infection caused by multidrug-resistant pathogens. Methods Medical records of patients who underwent hepatobiliary resection after preoperative external biliary drainage between 2001 and 2015 were reviewed retrospectively. Prophylactic antibiotics were selected according to the results of drug susceptibility tests of surveillance bile cultures. Results In total, 565 patients underwent surgical resection. Based on the results of bile cultures, the patients were classified into three groups: group A, patients with negative bile cultures (n = 113); group B, patients with positive bile cultures without multidrug-resistant pathogen growth (n = 416); and group C, patients with multidrug-resistant pathogen–positive bile culture (n = 36). The incidence of organ/space surgical site infection, bacteremia, median duration of postoperative hospital stay, and the mortality rate did not differ among the three groups. The incidence of incisional surgical site infection and infectious complications caused by multidrug-resistant pathogens was significantly higher in group C than in groups A and B. Fifty-two patients had postoperative infectious complications caused by multidrug-resistant pathogens. Multivariate analysis identified preoperative multidrug-resistant pathogen–positive bile culture as a significant independent risk factor for postoperative infectious complications caused by multidrug-resistant pathogens (P Conclusion Major hepatectomy with extrahepatic bile duct resection after biliary drainage can be performed with acceptable rates of morbidity and mortality using appropriate antibiotic prophylaxis, even in patients with biliary colonization/infection caused by multidrug-resistant pathogens.

While preoperative chemotherapy is frequently utilized before resection of non-neuroendocrine liver metastases, patients with resectable neuroendocrine liver metastases typically undergo surgery first. FAS is a cytotoxic chemotherapy regimen that is associated with substantial response rates in locally advanced and metastatic pancreatic neuroendocrine tumors. All patients who underwent R0/R1 resection of pancreatic neuroendocrine liver metastases at a single institution between 1998 and 2015 were included. The outcomes of patients treated with preoperative FAS were compared with those of patients who were not. Of the 67 patients included, 27 (40.3%) received preoperative FAS, whereas 40 (59.7%) did not. Despite being associated with higher rates of synchronous disease, lymph node metastases, and larger tumor size, patients who received preoperative FAS had similar overall survival [overall survival (OS), 108.2 months (95% confidence interval (CI) 78.0–136.0) vs. 107.0 months (95% CI 78.0–136.0), p = 0.64] and recurrence-free survival [RFS, 25.1 months (95% CI 23.2–27.0) vs. 18.0 months (95% CI 13.8–22.2), p = 0.16] as patients who did not. Among patients who presented with synchronous liver metastases (n = 46), the median OS [97.3 months (95% CI 65.9–128.6) vs. 65.0 months (95% CI 28.1–101.9), p = 0.001] and RFS [24.8 months (95% CI 22.6–26.9) vs. 12.1 months (2.2–22.0), p = 0.003] were significantly greater among patients who received preoperative FAS compared with those who did not. The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.

Inchinkoto (ICKT) is a popular choleretic and hepatoprotective herbal medicine that is widely used in Japan. Geniposide, a major ingredient of ICKT, is metabolized to genipin by gut microbiota, which exerts a choleretic effect. This study investigates the relationship between stool genipin-producing activity and diversity of the clinical effect of ICKT in patients with malignant obstructive jaundice. Fifty-two patients with malignant obstructive jaundice who underwent external biliary drainage were included. ICKT was administered as three packets per day (7.5 g/day) for three days and 2.5 g on the morning of the fourth day. Stool samples were collected before ICKT administration and bile flow was monitored on a daily basis. The microbiome, genipin-producing activity, and organic acids in stools were analyzed. The Shannon-Wiener (SW) index was calculated to evaluate gut microbiome diversity. The stool genipin-producing activity showed a significant positive correlation with the SW index. Stool genipin-producing activity positively correlated with the order Clostridia (obligate anaerobes), but negatively correlated with the order Lactobacillales (facultative anaerobes). Moreover, stool genipin-producing activity was positively correlated to the concentration valeric acid, but negatively correlated to the concentration of lactic acid and succinic acid. The change of bile flow at 2 and 3 days after ICKT administration showed significant positive correlation with genipin-producing activity (correlation coefficient, 0.40 and 0.29, respectively, P < 0.05). An analysis of stool profile, including stool genipin-producing activity, may predict the efficacy of ICKT. Modification of the microbiome may be a target to enhance the therapeutic effect of ICKT.

To evaluate the optimal duration of antimicrobial prophylaxis in patients undergoing "complicated"' major hepatectomy with extrahepatic bile duct resection.To date, 4 randomized controlled trials (RCTs) have assessed the duration of antimicrobial prophylaxis after hepatectomy. However, all of these previous studies involved only "simple" hepatectomy without extrahepatic bile duct resection.Patients with suspected hilar obstruction scheduled to undergo complicated hepatectomy after biliary drainage were randomized to 2-day (antibiotic treatment on days 1 and 2) or 4-day (on days 1 to 4) groups. Antibiotics were selected based on preoperative bile culture. The primary endpoint was the incidence of postoperative infectious complications.In total, 86 patients were included (43 patients in each arm) without between-group differences in baseline characteristics. Bile culture positivity was similar between the 2 groups. No significant between-group differences were observed in surgical variables. The incidence of any infectious complications was similar between the 2 groups (30.2% in the 2-day group and 32.6% in the 4-day group). The positive rate of systemic inflammatory response syndrome and the incidence of additional antibiotic use were almost identical between the 2 groups. According to Clavien-Dindo classification, grade 3a or higher complications occurred in 23 patients (53.5%) in the 2-day group and 29 patients (67.4%) in the 4-day group (P = 0.186). Postoperative hospital stay was not different between the 2 groups.Two-day administration of antimicrobial prophylaxis is sufficient for patients undergoing hepatectomy with extrahepatic bile duct resection [Registration number: ID 000009800 (University Hospital Medical Information Network, http://www.umin.ac.jp)].

Background Risk factors for pathological diaphragmatic invasion from colorectal liver metastases (CRLM) and differences in recurrence patterns and survival between patients with true pathological diaphragmatic invasion versus inflammatory adhesions only remain poorly understood. This study aimed at identifying risk factors for and survival impact of pathological diaphragmatic invasion in patients with CRLM. Methods Patients with CRLM who underwent hepatectomy with or without diaphragmatic resection from 1998 to 2015 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and recurrence patterns were examined according to the presence or absence of pathological invasion. Results Of 1860 patients, 70 underwent hepatectomy with diaphragmatic resection and 1799 had hepatectomy only. Among the patients with gross diaphragmatic involvement, 15 (21%) had pathological invasion, and 55 (79%) had inflammatory adhesion only. Multiple tumors (p = 0.019) and RAS mutation (p = 0.047) were significantly associated with pathological invasion. Pathological invasion was associated with a higher incidence of peritoneal recurrence (33% vs. 11%, p = 0.041), worse median RFS (6 months vs. 11 months, p = 0.21) and OS (26 months vs. 51 months, p = 0.046) compared to inflammatory adhesion. Conclusion Multiple tumors and RAS mutant were predictors for pathological diaphragmatic invasion, which was associated with a higher incidence of peritoneal recurrence and worse OS.

Background Minor hepatectomy following liver partition between the right anterior and posterior sectors requires technical ingenuities. In such hepatectomy, we used three-dimensional (3D) print; therefore, our procedure was introduced. Methods Digital segmentation of anatomical structures from multidetector-row computed tomography images utilized the original software 'PLUTO', which was developed by Graduate School of Information Science, Nagoya University. After changing the final segmentation data to the stereolithography files, 3D-printed liver at 70% scale was produced. The support material was washed and mould charge was removed from 3D-printed hepatic veins. The surface of 3D-printed model was abraded and coated with urethane resin paint. After natural drying, 3D-printed hepatic veins were coloured by injection of a dye. The 3D-printed portal veins were whitish because mould charge remained. All procedures after 3D printing were performed by hand work. A 3D-printed model of the right posterior sector and a 3D-printed model of other parenchyma were produced, respectively. Measuring the length between the main structures on the liver surface and the planned partition line on the 3D-printed model, land mark between the right anterior and posterior sectors on the real liver surface was produced with scale adjustment. Results Minor hepatectomy following liver partition between the right anterior and posterior sectors was performed referring to 3D-printed model. The planned liver partition and resection were successful. Conclusions Application of 3D-printed liver to minor hepatectomy following liver partition between the right anterior and posterior sectors is easy and a suitable procedure.