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Background: Survival in patients with retroperitoneal liposarcoma (RPLS) depends on the surgical management of the dedifferentiated foci. The present study investigated the diagnostic yield of contrast-enhanced CT, 18F-fluorodeoxyglucose positron emission tomography (PET), and diffusion-weighted MRI in terms of dedifferentiated foci within the RPLS. Methods: Patients treated with primary or recurrent RPLS who underwent the above imaging between January 2010 and December 2021 were retrospectively reviewed. The diagnostic accuracy of the three modalities for histologic subtype of dedifferentiated liposarcoma (DDLS) and French Federation of Cancer Center (FNCLCC) grade 2/3 were compared using receiver operating characteristic curves and areas under the curves (AUCs). Results: The cohort involved 32 patients with 53 tumors; 30 of which exhibited DDLS and 31 of which did FNCLCC grades 2/3. The optimal thresholds for predicting DDLS were mean CT value of 31 Hounsfield Unit (HU) (AUC = 0.880, 95% CI 0.775–0.984; p

The aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status.Seventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0-1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately.The rates of traditional R0 (RM 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005).Narrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.

Standardized criteria for drain removal in hepatobiliary resection are lacking. Here, we evaluated the outcomes of delayed removal policy in this extended surgery.Patients undergoing hepatectomy with biliary reconstruction between 2012 and 2018 were retrospectively reviewed. The drains were removed on postoperative day (POD) 7 when the drainage fluid was grossly serous, biochemically normal, and negative for bacterial contamination as assessed by Gram staining; additionally, no abnormal fluid collection was confirmed by computed tomography. Clinically relevant abdominal complications (CRACs), including biliary leakage, pancreatic fistula or intra-abdominal abscess, served as the primary outcome measure.Among 374 study patients, surgical drains were removed in 166 (44.3%) patients who met the criteria. Of these patients, 16 (9.6%) patients subsequently required additional drainage due to CRAC. Drains were retained and exchanged in 208 (55.6%) patients who did not meet the criteria. Of these, exchanged drains were soon removed in 34 patients due to no signs of CRAC. The diagnostic ability of the criteria revealed 0.916 sensitivity, 0.815 specificity, and 0.866 accuracy.The four findings on POD 7 worked well as criteria for drain removal, and these criteria may be helpful in drain management after hepatobiliary resection.

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.

Understanding the long-term redox conditions and the related carbon cycle in groundwater is essential for long-term safety assessment because they affect the performance of barrier systems and radionuclide transport in geological disposal. However, it is difficult to identify those long-term changes directly. To help understand this, we conducted a paleohydrogeological study on calcite mineralization associated with fracture-controlled groundwater flow-paths in the Toki Granite in central Japan, focusing on its carbon and oxygen stable isotope characteristics. Previous studies revealed four generations of fracture-filling calcite in the Toki Granite. Therefore, we conducted isotopic analysis on both bulk samples of calcite and spatially-resolved microsamples of discrete generations of calcite within zoned crystals. The δ18OVPDB of calcite ranging between −32.7‰ to −0.59‰ revealed that the groundwater that precipitated the calcite was derived from various origins over the geological history of the area, including early hydrothermal fluids associated with the late-stage cooling of the granite (less than −17.2‰); freshwater invasion from the surface following regional uplift (−18.5‰∼ −8.3‰), and; seawater that penetrated during periods of marine transgression (−8.7‰ ∼ −0.3‰). The range in δ13CVPDB values (−56.5‰ ∼ +6.0‰) was wider than the isotopic range of dissolved inorganic carbon (DIC) that originated from hydrothermal, meteoric, and seawater sources (−25‰ ∼ +2‰). Calcite with low δ13CVPDB values less than −25‰ is believed to have precipitated from groundwater with DIC that was provided by anaerobic oxidation of methane (AOM), whereas calcite with δ13CVPDB higher than +2‰ is believed to have precipitated from groundwater containing 13C-enriched DIC as a carbon source derived during methanogenesis. These processes influencing the formation of calcite mineralization in the Toki Granite are comparable to those at other crystalline rock sites in European countries. The AOM calcite and calcite associated with methanogenesis in the Toki Granite precipitated during the transition of the groundwater origin from meteoric to seawater. Understanding these redox processes and the related carbon cycle in granitic groundwater can provide important insights into processes relevant to assessing the long-term evolution of geoenvironmental systems.

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.

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.

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.

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.

Summary Late-onset postoperative pneumonia (LOPP) after esophagectomy is poorly understood. This study was designed to clarify the features and risk factors for this event. Patients who underwent esophagectomy for esophageal cancer between 2006 and 2016 were included. LOPP was defined as radiologically proven pneumonia that occurred over 3 months after surgery, and clinically relevant late-onset postoperative pneumonia (CR-LOPP) was defined as LOPP that required administration of oxygen and antibiotics in the hospital and/or more intensive treatment. The total psoas muscle area (TPA) was measured using preoperative and postoperative (at 3 months after surgery) computed tomography scan images. Potential risk factors for CR-LOPP were investigated. Among 175 study patients, 46 (26.3%) had LOPP, 29 (16.6%) of whom exhibited CR-LOPP with a cumulative incidence of 15.6% at 3 years and 22.4% at 5 years. Four (13.8%) of these patients died of LOPP. Univariable analysis showed that clinical stage ≥III (P = 0.005), preoperative prognostic nutritional index (PNI) 5% (HR 9.93, P

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.

The first total synthesis of three echinodermatous sialyl inositol phosphosphingolipids, which exhibit unusual neuritogenic activity in the absence of nerve growth factor, are reported. Highlights of the syntheses include 9- O-methylation on sialic acid, inter-residual amide bond formation between sialic acid residues, and highly stereo- and regioselective sialylation of inositol. A key phosphodiester linkage between the mono-, di-, and trisialyl inositols and ceramide was formed at a late state employing the phosphoramidite method.

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.

Familial Mediterranean fever (FMF) is an inherited autoimmune disease characterized by periodic fevers and serositis. Most cases have been diagnosed within 10 years or less; however, there have been no reports of cases in which diagnosis was delayed for several decades. In this study, we encountered a case of FMF in which the patient had recurrent unexplained fevers since childhood, but diagnosis was delayed for more than 30 years due to a psychiatric disorder. Our findings showed that a possible reasons for this delay are possibility of neglect or parenting skills issues, little knowledge of FMF in Japan and the lack of social connections due to the patient's underlying mental illness. We suggest that it is important to conduct a thorough medical interview to identify FMF, as it may go undiagnosed, especially when the patient has few social ties.

This study has focused on the formation sequence and Rare earth elements with yttrium (REY) of fracture-filling calcite in the Toki Granite in the Mizunami area, central Japan. The morphological, chemical, and isotopic characteristics of the calcite and chemistry of fluid inclusions reveal that the calcite in the Toki Granite can be differentiated into four discrete generations: Calcite I (oldest) to Calcite IV (most recent). The precipitation history of calcite reflects the changes in the hydrogeochemical regime of paleo-groundwaters, controlled by the evolution of groundwater by seawater infiltration associated with marine transgression and surface water infiltration associated with marine regression and uplift. The post-Archean average shale-normalized REY patterns in generations of calcite show no significant Ce anomaly, negative Eu anomaly, and light REY (LREY)-depleted pattern in dominates. These features are also common to the Toki Granite. The consistency of the features in each generation of calcite indicates that REY was supplied from the Toki Granite by water-rock interaction. The lack of a Ce anomaly in the calcite demonstrates that groundwaters have maintained reducing conditions during the calcite precipitation. However, the fractionation of LREY and heavy REY (HREY) in each generation of the calcite is more pronounced than in the granite. The fractionation process in the paleo-groundwaters from which each generation of calcite precipitated closely relates to the systematic variation of carbonate complex in REY series and/or pH in palaeo-groundwater. The findings of this study will be necessary for assessing the long-term safety of geological disposal of high-level radioactive waste.

The standard chemotherapy regimen for unresectable or recurrent biliary tract cancer is gemcitabine combined with cisplatin (GC). To evaluate the effectiveness and safety of chemotherapy in patients with unresectable or recurrent biliary tract cancer in the real world, we retrospectively analyzed the clinical courses of patients who underwent chemotherapy with GC from January 2015 to November 2019. Forty-eight patients underwent the GC regimen. One patient (2.1%) achieved a complete response, seven patients (14.6%) achieved a partial response, 26 patients (54.2) achieved stable disease, 11 patients (22.9%) achieved progressive disease, and 3 patients (6.3%) were not evaluable. The overall response rate was 16.7%. The median overall survival was 14.2 months (95% CI: 13.8–14.6), and the median progression-free survival was 7.7 months (95% CI: 4.2–11.2). Thirty-nine patients (81.3%) experienced grade 3 or higher severe adverse events as follows: 54.2% experienced neutropenia, 20.8% experienced anemia, 12.5% experienced thrombocytopenia and 20.8% experienced biliary tract infection. As a second-line chemotherapy, S-1 was used in seventeen patients, and stable disease was achieved in three patients (17.6%). The GC regimen for biliary tract cancer is effective and safe for unresectable or recurrent biliary tract cancer in routine clinical practice.

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.

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.

Redox-active porous ionic crystals based on polyoxometalate (POM) were utilized to form and stabilize small mixed-valence luminescent silver clusters via cation-coupled electron-transfer (CCET) reactions. Reduction-induced ion-exchange between Cs+ and Ag+via CCET took less than 1 min to complete and consisted of two steps: electron transfer from reduced POM to Ag+ and the subsequent formation of a silver cluster, and diffusion of the silver cluster and exchange with Cs+. Notably, the simple ion-exchange took more than 24 h. The compound containing the silver cluster showed high affinity toward unsaturated hydrocarbon guests.

BACKGROUND: In patients undergoing resection of intrahepatic cholangiocarcinoma (ICC), hypervascularity during the arterial phase of contrast-enhanced computed tomography (CT) is associated with better prognosis than hypovascularity. However, the prognostic implications of arterial enhancement pattern in patients with unresectable ICC are unknown. We assessed the prognostic implications of arterial enhancement pattern in patients with resectable and unresectable ICC. METHODS: Consecutive patients who underwent surgery or gemcitabine-plus-cisplatin chemotherapy for ICC during 2003–2015 and CT with dynamic enhancement for diagnosis were included. After review by 2 radiologists, tumors were categorized according to the percentage of the tumor exhibiting arterial enhancement as hypervascular (>50% of tumor exhibiting enhancement), peripherally enhancing(10%−50%), and hypovascular (