Replication of Akabane virus and related orthobunyaviruses in a fetal-bovine-brain-derived cell line.

Akabane virus (AKAV), Aino virus, Peaton virus, Sathuperi virus, and Shamonda virus are arthropod-borne viruses belonging to the order Elliovirales, family Peribunyaviridae, genus Orthobunyavirus. These viruses cause or may cause congenital malformations in ruminants, including hydranencephaly, poliomyelitis, and arthrogryposis, although their pathogenicity may vary among field cases. AKAV may cause relatively severe congenital lesions such as hydranencephaly in calves. Furthermore, strains of AKAV genogroups I and II exhibit different disease courses. Genogroup I strains predominantly cause postnatal viral encephalomyelitis, while genogroup II strains are primarily detected in cases of congenital malformation. However, the biological properties of AKAV and other orthobunyaviruses are insufficiently investigated in hosts in the field and in vitro. Here, we used an immortalized bovine brain cell line (FBBC-1) to investigate viral replication efficiency, cytopathogenicity, and host innate immune responses. AKAV genogroup II and Shamonda virus replicated to higher titers in FBBC-1 cells compared with the other viruses, and only AKAV caused cytopathic effects. These results may be associated with the severe congenital lesions in the brain caused by AKAV genogroup II. AKAV genogroup II strains replicated to higher titers in FBBC-1 cells than AKAV genogroup I strains, suggesting that genogroup II strains replicated more efficiently in fetal brain cells, accounting for the detection of the latter strains mainly in fetal infection cases. Therefore, FBBC-1 cells may serve as a valuable tool for investigating the virulence and tropism of the orthobunyaviruses for bovine neonatal brain tissues in vitro.

Laparoscopic and open minor liver resection for hepatocellular carcinoma with clinically significant portal hypertension: a multicenter study using inverse probability weighting approach.

BACKGROUND: Liver resection offers substantial advantages over open liver resection (OLR) for patients with hepatocellular carcinoma (HCC) in terms of reduced intraoperative blood loss and morbidity. However, there is limited evidence comparing the indications and perioperative outcomes with the open versus laparoscopic approach for resection. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection (LLR) and OLR for HCC with clinically significant portal hypertension (CSPH). METHODS: A total of 316 HCC patients with CSPH (the presence of gastroesophageal varices or platelet count < 100,000/ml and spleen diameter > 12 cm) undergoing minor liver resection at eight centers were included in this study. To adjust for confounding factors between the LLR and OLR groups, an inverse probability weighting method analysis was performed. RESULTS: Overall, 193 patients underwent LLR and 123 underwent OLR. After weighting, LLR was associated with a lower volume of intraoperative blood loss and the incidence of postoperative complications (including pulmonary complications, incisional surgical site infection, and paralytic ileus) compared to the OLR group. The 3-, 5-, and 7-year postoperative recurrence-free survival rates were 39%, 26%, and 22% in the LLR group and 49%, 18%, and 18% in the OLR group, respectively (p = 0.18). And, the 3-, 5-, and 7-year postoperative overall survival rates were 71%, 56%, and 44% in the LLR group and 76%, 51%, 44% in the OLR group, respectively (p = 0.87). CONCLUSIONS: LLR for HCC patients with CSPH is clinically advantageous by lowering the volume of intraoperative blood loss and incidence of postoperative complications, thereby offering feasible long-term survival.

Bilateral hibernomas in the femoral regions of a dog.

A 14-year-old intact male Chihuahua dog was presented with masses located between the biceps femoris and adductor muscles in both hind limbs. Based on histopathological, immunohistochemical, and ultrastructural findings, we diagnosed these masses as bilateral hibernomas in the femoral regions. The dog had no evidence of recurrence or metastasis of the hibernomas through a 4-month postoperative follow-up. This is apparently the first report of bilateral hibernomas in the femoral regions of a dog. Key clinical message: Bilateral hibernomas should be considered as a differential diagnosis for masses occurring in the femoral regions of dogs.

Hibernomes bilatéraux dans les régions fémorales d'un chien. Un chien Chihuahua mâle intact de 14 ans a été présenté avec des masses situées entre le biceps fémoral et les muscles adducteurs des deux membres postérieurs. Sur la base des résultats histopathologiques, immunohistochimiques et ultrastructuraux, nous avons diagnostiqué ces masses comme des hibernomes bilatéraux dans les régions fémorales. Le chien n'avait aucun signe de récidive ou de métastases des hibernomes au cours d'un suivi postopératoire de 4 mois. Il s'agit apparemment du premier rapport d'hibernome bilatéral dans les régions fémorales d'un chien.Message clinique clé:Les hibernomes bilatéraux doivent être considérés comme un diagnostic différentiel pour les masses survenant dans les régions fémorales des chiens.(Traduit par Dr Serge Messier).

The Prognostic Value of Preoperative Serum Markers and Risk Classification in Patients with Hepatocellular Carcinoma.

BACKGROUND: Complex hepatocellular carcinoma (HCC) prognostic biomarkers have been reported in various studies. We aimed to establish biomarkers that could predict prognosis, and formulate a simple classification using non-invasive preoperative blood test data. METHODS: We retrospectively identified 305 patients for a discovery cohort who had undergone HCC-related hepatectomy at four Japanese university hospitals between January 1, 2011 and December 31, 2013. Preoperative blood test parameter optimal cut-off values were determined using receiver operating characteristic curve analysis. Cox uni- and multivariate analyses were used to determine independent prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. Validation was performed with 267 patients from three other hospitals. RESULTS: In multivariate analysis, α-fetoprotein (AFP, p < 0.001), protein induced by vitamin K absence or antagonist-II (PIVKA-II, p = 0.006), and C-reactive protein (CRP, p < 0.001) were independent prognostic factors for overall survival (OS). AFP (p = 0.007), total bilirubin (p = 0.001), and CRP (p = 0.003) were independent recurrent risk factors for recurrence-free survival (RFS). CART analysis results formed OS (CRP, AFP, and albumin) and RFS (PIVKA-II, CRP, and total bilirubin) decision trees, based on machine learning using preoperative serum markers, with three risk classifications. Five-year OS (low risk, 80.0%; moderate risk, 56.3%; high risk, 25.2%; p < 0.001) and RFS (low risk, 43.4%; moderate risk, 30.8%; high risk, 16.6%; p < 0.001) risks differed significantly. These classifications also stratified OS and RFS risk in the validation cohort. CONCLUSION: Three simple risk classifications using preoperative non-invasive prognostic factors could predict prognosis.

Efficacy and safety of tazobactam/ceftolozane in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice.

INTRODUCTION: This single-center study evaluated the efficacy and safety of tazobactam/ceftolozane (TAZ/CTLZ) in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice. METHODS: This study included 50 patients, including 35 with intraabdominal abscess or peritonitis, 5 with liver abscess, 4 with cholecystitis, and 6 with cholangitis with sepsis. Of the 50 patients, 29 received TAZ/CTLZ and metronidazole after a prior antibacterial therapy failure, including tazobactam/piperacillin, cefmetazole, and levofloxacin. Source control was performed in 36 patients. RESULTS: The clinical response could be evaluated in 49 patients. The clinical cure rate at end-of-therapy was 91.8% (45 of 49 patients) and that at test-of-cure was 89.6% (43 of 48 patients). Of 5 patients in whom clinical response at test-of-cure was a failure, 1 developed infectious disease during chemoradiotherapy for recurrent cancer and 4 after liver resection or pancreatoduodenectomy. Three of the 4 patients were associated with pancreatic juice leakage. Isolated pathogens were eradicated or presumably eradicated in 27 of 31 (87.1%) patients in whom microbiological response at test-of-cure could be evaluated. The response rate for AmpC-producing Enterobacteriaceae was 87.5%. Nausea was observed in two patients. Aspartate and alanine aminotransferase activities were increased in 3 of the 50 (6.0%) patients. The activities improved after the antibiotic discontinuation. CONCLUSIONS: This observational study demonstrated that TAZ/CTLZ in combination with metronidazole has a favorable effect without major drug-related adverse events for intraabdominal infection in the hepato-biliary-pancreatic field in clinical practice although the efficacy of TAZ/CTLZ may decrease in compromised patients.

Pancreaticoduodenectomy with celiac artery resection (PD-CAR) for unresctable locally advanced pancreatic ductal adenocarcinoma.

PURPOSE: Locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) involving the celiac artery (CeA), the common hepatic artery and the gastroduodenal artery (GDA) is considered unresectable. We developed the novel procedure of pancreaticoduodenectomy with celiac artery resection (PD-CAR) for such LA-PDACs. METHODS: From 2015 to 2018, we performed curative pancreatectomy with major arterial resection for 13 LA-PDACs as a clinical study (UMIN000029501). Of those, four patients with pancreatic neck cancer involving the CeA and GDA were candidates for PD-CAR. Prior to surgery, blood flow alterations were performed to unify the blood flow to the liver, stomach, and pancreas, resulting in feeding from the cancer-free artery. During PD-CAR, arterial reconstruction of the unified artery was performed as needed. Based on the records of PD-CAR cases, we retrospectively analyzed the validity of the operation. RESULTS: R0 resection was achieved in all patients. Arterial reconstruction was performed in three patients. In another patient, the hepatic arterial flow was maintained by preserving of the left gastric artery. The mean operative time was 669 min, and the mean blood loss was 1003 ml. Although Clavien-Dindo classification III-IV postoperative morbidities occurred in three patients, no reoperations nor mortalities occurred. Although two patients died of cancer recurrence, one patient survived for 26 months without recurrence (died of cerebral infarction), and another is alive at 76 months without recurrence. CONCLUSION: PD-CAR, which enabled R0 resection and preservation of the residual stomach, pancreas, and spleen, provided acceptable postoperative outcomes.

Interleukin-8 produced from cancer-associated fibroblasts suppresses proliferation of the OCUCh-LM1 cancer cell line.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort. METHODS: We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines on cancer cell proliferation. RESULTS: PDAC patients with positive αSMA expression showed significantly shorter overall survival and recurrence-free survival than αSMA-negative patients (p = 0.003, p = 0.009, respectively). BTC patients with positive αSMA expression showed better recurrence-free survival than αSMA-negative patients (p = 0.03). CAF-conditioned medium suppressed the proliferation of cancer cells for only OCUCh-LM1 cells and not PDAC cells. Blockage of Interleukin-8 (IL-8) or its receptor C-X-C motif chemokine receptor 2 (CXCR2) by antibodies canceled the suppressive effect of the IL-8. CONCLUSIONS: CAFs are a good prognostic factor in BTC, but not for PDAC. Moreover, CAF-produced Interleukin-8 suppresses the proliferation of OCUCh-LM1 cell lines.

Laparoscopic liver resection reduces postoperative infection in patients with hepatocellular carcinoma: a propensity score-based analysis.

BACKGROUND: This study is aimed to compare the occurrence of postoperative infections between patients with hepatocellular carcinoma (HCC) undergoing laparoscopic liver resection (LLR) and those undergoing open liver resection (OLR). METHODS: This study included 446 patients who underwent initial curative liver resection for HCC 5 cm or less in size without macroscopic vascular invasion. To adjust for confounding factors between the LLR and OLR groups, propensity score matching and inverse probability weighting (IPW) analysis were performed. The incidence rates of postoperative infection, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI), were compared between the two groups. RESULTS: An imbalance in several confounding variables, including period of surgery, extent of liver resection, difficult location, proximity to a major vessel, tumor size ≥ 3 cm, and multiple tumors, was observed between the two groups in the original cohort. After matching and weighting, the imbalance between the two groups significantly decreased. Compared with OLR, LLR was associated with a lower volume of intraoperative blood loss (140 vs. 350 mL, P < 0.001 in the matched cohort; 120 vs. 320 mL, P < 0.001 in the weighted cohort) and reduced risk of postoperative infection (2.0% vs. 12%, P = 0.015 in the matched cohort; 2.9% vs. 14%, P = 0.005 in the weighted cohort). Of the types of postoperative infections, organ/space SSI and RI were less frequently observed in the LLR group than in the OLR group in the matched cohort (1.0% vs. 6.0%, P = 0.091 for organ/space SSI; 0% vs. 6.0%, P < 0.001 for RI) and in the weighted cohort (1.2% vs. 7.8%, P < 0.001 for organ/space SSI; 0.3% vs. 5.1%, P = 0.009 for RI). CONCLUSIONS: Compared with OLR, LLR for HCC might reduce postoperative infections, including organ/space SSI and RI.

Prognostic Factors and Lymph Node Metastasis Patterns of Primary Duodenal Cancer.

BACKGROUND: The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. METHODS: Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. RESULTS: The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. CONCLUSIONS: Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

Treatment strategy for resectable colorectal cancer liver metastases from the viewpoint of time to surgical failure.

PURPOSE: The efficacy of pre or postoperative chemotherapy for resectable colorectal cancer liver metastases (CRLM) is disputed. This study aimed to examine the risk factors for time to surgical failure (TSF) and analyze the efficacy of pre or postoperative chemotherapy prior to liver resection for CRLM. METHODS: The clinicopathological factors of 567 patients who underwent initial hepatectomy for CRLM at 7 university hospitals between April 2007 and March 2013 were retrospectively analyzed. The prognostic factors were identified and then stratified into two groups according to the number of preoperative prognostic factors: the high-score group (H-group, score 2-4) and the low-score group (L-group, score 0 or 1). RESULTS: Patients who experienced unresectable recurrence within 12 months after initial treatment had a significantly shorter prognosis than other patients (p < 0.001). Multivariate analysis identified age ≥ 70 (p = 0.001), pT4 (p = 0.015), pN1 (p < 0.001), carbohydrate antigen 19-9 ≥ 37 U/ml (p = 0.002), Clavien-Dindo grade ≥ IIIa (p = 0.013), and postoperative chemotherapy (p = 0.006) as independent prognostic factors. In the H-group, patients who received chemotherapy had a better prognosis than those who did not (p = 0.001). CONCLUSION: Postoperative chemotherapy is beneficial in colorectal cancer patients with more than two of the following factors: age ≥ 70, carbohydrate antigen 19-9-positivity, pT4, and lymph node metastasis.

Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma.

BACKGROUND: We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin × Lymphocyte)/(CRP × 104). Patients with a CALLY index ≥5 (n = 200) were compared to those with an index <5 (n = 184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort). RESULTS: The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p = 0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5: 71% vs. <5: 46%; p < 0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p < 0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort. CONCLUSION: The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.

Preoperative Risk Assessment for Loss of Independence Following Hepatic Resection in Elderly Patients: A Prospective Multicenter Study.

OBJECTIVE: To establish a preoperative risk assessment method for loss of independence after hepatic resection. SUMMARY BACKGROUND DATA: Hepatic resection often results in loss of independence in preoperatively self-sufficient elderly people. Elderly patients should therefore be carefully selected for surgery. METHODS: In this prospective, multicenter study, 347 independently-living patients aged ≥65 years, scheduled for hepatic resection, were divided into study (n = 232) and validation (n = 115) cohorts. We investigated the risk factors for postoperative loss of independence in the study cohort and verified our findings with the validation cohort. Loss of independence was defined as transfer to a rehabilitation facility, discharge to residence with home-based healthcare, 30-day readmission for poor functionality, and 90-day mortality (except for cancer-related deaths). RESULTS: In the study cohort, univariate and multivariate analyses indicated that frailty, age ≥ 76 years, and open surgery were independent risk factors for postoperative loss of independence. Proportions of patients with postoperative loss of independence in the study and validation cohorts were respectively 3.0% and 0% among those with no applicable risk factors, 8.1% and 12.5% among those with 1 applicable risk factor, 25.5% and 25.0% among those with 2 applicable risk factors, and 56.3% and 50.0% among those with all 3 factors applicable (P < 0.001 for both cohorts). Areas under the receiver operating characteristic curves for the study and validation groups were 0.777 and 0.783, respectively. CONCLUSIONS: Preoperative risk assessments using these 3 factors may be effective in predicting and planning for postoperative loss of independence after hepatic resection in elderly patients.

Postoperative direct-acting antiviral treatment after liver resection in patients with hepatitis C virus-related hepatocellular carcinoma.

AIM: We investigated effects of direct-acting antiviral (DAA)-induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) for postoperative recurrence and survival. METHODS: Surgical outcomes in 18 patients with postoperative DAA-induced SVR (HCC-DAA group) were compared with those in 23 patients with preoperative DAA-induced SVR (DAA-HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence <1 year after surgery were excluded. RESULTS: Serum concentrations of aminotransferases improved 1 year after surgery in both the HCC-DAA and DAA-HCC groups. The number of HCC-DAA patients with albumin-bilirubin (ALBI) grade 1 increased from 11 to 15. The disease-free survival rate did not differ between HCC-DAA group (3 years, 60%) and the other two groups (DAA-HCC group, 92% and control group, 60%). The 3-year overall survival rates were better in the DAA-HCC group (84%) and HCC-DAA group (100%) than in the control group (46%; all ps < 0.05 according to Holm's test). Multivariable analysis revealed that tumor stage was an independent risk factor for postoperative recurrence, and ALBI grade at 1 year after surgery was predictive of postoperative survival, but DAA-induced SVR was neither. CONCLUSIONS: Although postoperative DAA-induced SVR itself may not suppress postoperative recurrence, improvement in liver function as a result of DAA administration after surgery may prolong postoperative survival.

Impact of Advancing Age on the Status and Risk of Postoperative Infections After Liver Resection.

BACKGROUND: Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status. METHODS: This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively). RESULTS: Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29). CONCLUSIONS: Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years.

Multifocal origin of occupational cholangiocarcinoma revealed by comparison of multilesion mutational profiles.

Recently identified occupational cholangiocarcinoma among printing workers is characterized by chronic bile duct injuries and precancerous or early cancerous lesions at multiple sites of the bile ducts. These observations suggested the potential multifocal carcinogenesis of the disease. We performed whole-exome analysis of multiple lesions, including the invasive carcinomas and precancerous lesions of four occupational cholangiocarcinoma cases. A much higher mutation burden was observed in both the invasive carcinomas (mean 76.3/Mb) and precancerous lesions (mean 71.8/Mb) than in non-occupational cholangiocarcinomas (mean 1.6/Mb). Most somatic mutations identified in 11 of 16 lesions did not overlap with each other. In contrast, a unique trinucleotide mutational signature of GpCpY to GpTpY was shared among the lesions. These results suggest that most of these lesions are multiclonal in origin and that common mutagenic processes, which may be induced by exposure to haloalkanes or their metabolites, generated somatic mutations at different sites of the bile ducts. A similarly high mutation rate had already been identified in the precancerous lesions, implying an increased potential for carcinogenesis throughout the biliary tree. These genomic features support the importance of ongoing close follow-up of the patients as a group at high risk of recurrence.

Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis.

BACKGROUND & AIMS: Treatment allocation in patients with hepatocellular carcinoma (HCC) on a background of Child-Pugh B (CP-B) cirrhosis is controversial. Liver resection has been proposed in small series with acceptable outcomes, but data are limited. The aim of this study was to evaluate the outcomes of patients undergoing liver resection for HCC in CP-B cirrhosis, focusing on the surgical risks and survival. METHODS: Patients were retrospectively pooled from 14 international referral centers from 2002 to 2017. Postoperative and oncological outcomes were investigated. Prediction models for surgical risks, disease-free survival and overall survival were constructed. RESULTS: A total of 253 patients were included, of whom 57.3% of patients had a preoperative platelet count <100,000/mm3, 43.5% had preoperative ascites, and 56.9% had portal hypertension. A minor hepatectomy was most commonly performed (84.6%) and 122 (48.2%) were operated on by minimally invasive surgery (MIS). Ninety-day mortality was 4.3% with 6 patients (2.3%) dying from liver failure. One hundred and eight patients (42.7%) experienced complications, of which the most common was ascites (37.5%). Patients undergoing major hepatectomies had higher 90-day mortality (10.3% vs. 3.3%; p = 0.04) and morbidity rates (69.2% vs. 37.9%; p <0.001). Patients undergoing an open hepatectomy had higher morbidity (52.7% vs. 31.9%; p = 0.001) than those undergoing MIS. A prediction model for surgical risk was constructed (https://childb.shinyapps.io/morbidity/). The 5-year overall survival rate was 47%, and 56.9% of patients experienced recurrence. Prediction models for overall survival (https://childb.shinyapps.io/survival/) and disease-free survival (https://childb.shinyapps.io/DFsurvival/) were constructed. CONCLUSIONS: Liver resection should be considered for patients with HCC and CP-B cirrhosis after careful selection according to patient characteristics, tumor pattern and liver function, while aiming to minimize surgical stress. An estimation of the surgical risk and survival advantage may be helpful in treatment allocation, eventually improving postoperative morbidity and achieving safe oncological outcomes. LAY SUMMARY: Liver resection for hepatocellular carcinoma in advanced cirrhosis (Child-Pugh B score) is associated with a high rate of postoperative complications. However, due to the limited therapeutic alternatives in this setting, recent studies have shown promising results after accurate patient selection. In our international multicenter study, we provide 3 clinical models to predict postoperative surgical risks and long-term survival following liver resection, with the aim of improving treatment allocation and eventually clinical outcomes.

Selective Convergence to Atropisomers of a Porphyrin Derivative Having Bulky Substituents at the Periphery.

Four kinds of possible atropisomers of a porphyrin derivative (1), having mesityl groups at one of the o-positions of each meso-aryl group, can be selectively converged to targeted atropisomers among the four isomers (αααα, αααß, αßαß, and ααßß) under appropriate conditions for each atropisomer. For example, protonation and subsequent neutralization of a free base porphyrin (H2-1) induces a convergence reaction to the αßαß atropisomer, H2-1-αßαß, from an atropisomeric mixture. The αααα isomer, H2-1-αααα, was also obtained by heating a solution of H2-1 in CHCl3 in 60% isolated yield, probably owing to a template effect of the solvent molecule. Remarkably, when an atropisomeric mixture of its zinc complex, Zn-1, was heated at 70 °C in a ClCH2CH2Cl/MeOH mixed solvent, crystals composed of only Zn-1-αααα were formed. The hydrophobic space formed by the four mesityl groups in the αααα isomer can be used for repeatable molecular encapsulation of benzene, and the encapsulation structure was elucidated by powder X-ray diffraction analysis. Heating the solid of an atropisomeric mixture of Zn-1 to 400 °C afforded the ααßß isomer almost quantitatively. On the other hand, the solid of H2-1-αααα can be converted by heating, successively to H2-1-αααß at 286 °C and then to H2-1-ααßß at 350 °C.

Surgical outcomes for hepatocellular carcinoma detected after hepatitis C virus eradiation by direct-acting antivirals.

OBJECTIVE: To investigate the postoperative recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after liver resection in patients with and without the achievement of sustained virologic response (SVR) through the administration of direct-acting antivirals (DAA). METHODS: Among 28 patients with HCC detected after DAA-SVR (DAA group) and 197 patients with HCC who did not receive treatment for HCV infection or who did not achieve an SVR (control group) between January 2000 and July 2019, we performed propensity score matching (PSM) to avoid confounding differences between the two groups. RESULTS: After PSM, 28 patients in each group were selected for analysis. The DAA-SVR patients showed improved liver function at operation and at recurrence in comparison to the control group. The disease-free survival rate at 3 years after surgery was 69% in the DAA group and 35% in the control group, respectively (P = .021). In the DAA group, all three patients with recurrence met the Milan criteria and could be managed by curative treatments and none died of liver failure during the follow-up period. CONCLUSIONS: SVR status suppresses postoperative recurrence of HCV-related HCC detected after DAA-SVR. Improved liver function may contribute to the successful treatment and prevention of liver failure.

Identification and characterization of a novel orbivirus, Yonaguni orbivirus, isolated from cattle on the westernmost island of Japan.

A novel orbivirus (genus Orbivirus, family Reoviridae), designated Yonaguni orbivirus (YONOV), was isolated from bovine blood collected on a subtropical island of Japan in 2015. The YONOV genome (20,054 nucleotides in total) has a coding arrangement similar to those of mosquito-borne orbiviruses. YONOV has a close genetic relationship to mosquito-borne orbiviruses, especially to Mobuck virus (MBV), which was isolated in North America. However, YONOV and MBV share less than 74% nucleotide sequence identity in the major subcore protein (T2) coding sequence, which satisfies the criterion for species demarcation. It is still uncertain whether YONOV should be assigned to a novel species in the genus Orbivirus.

Validation and performance of three-level procedure-based classification for laparoscopic liver resection.

BACKGROUND: A procedure-based laparoscopic liver resection (LLR) classification (IMM classification) stratified 11 different LLR procedures into 3 grades. IMM classification assessed the difficulty of LLR differently than an index-based LLR classification (IWATE criteria), which scored each procedure on an index scale of 12. We validated the difference of 3 IMM grades using an external cohort, evaluated the IMM classification using the scores of the IWATE criteria, and compared the performance of IMM classification with the IWATE criteria and the minor/major classification. METHODS: Patients undergoing LLR without simultaneous procedures were selected from a prospectively maintained database at the Institut Mutualiste Montsouris (IMM cohort) and from the database of 43 Japanese institutions (JMI cohort). Surgical and postoperative outcomes were evaluated according to the 3 IMM grades using the JMI cohort. The 11 LLR procedures included in the IMM classification were scored according to the IWATE criteria. The area under the curves (AUCs) for surgical and postoperative outcomes were compared. RESULTS: In the JMI (n = 1867) cohort, operative time, blood loss, conversion rate, and major complication rate were significantly associated with a stepwise increase in grades from I to III (all, P < 0.001). In the IMM (n = 433) and JMI cohorts, IMM grades I, II, and III corresponded to three low-scoring, two intermediate-scoring, and six high-scoring LLR procedures as per the IWATE criteria, respectively. Mean ± standard deviation among the IMM grades were significantly different: 3.7 ± 1.4 (grade I) versus 7.5 ± 1.7 (grade II) versus 10.2 ± 1.0 (grade III) (P < 0.001) in the IMM cohort and 3.6 ± 1.4 (grade I) versus 6.7 ± 1.5 (grade II) versus 9.3 ± 1.4 (grade III) (P < 0.001) in the JMI cohort. The AUCs for surgical and postoperative outcomes are higher for the 3-level IMM classification than for the minor/major classification. CONCLUSIONS: The difference of 3 IMM grades with respect to surgical and postoperative outcomes was validated using an external cohort. The 3-level procedure-based IMM classification was in accordance with the index-based IWATE criteria. The IMM classification performed better than the minor/major classification for stratifying LLR procedures.