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Anatomic liver resection (ALR) has been established to eliminate the tumor-bearing hepatic region with preservation of the remnant liver volume for liver malignancies. Recently, laparoscopic ALR has been widely applied; however, there are few reports on laparoscopic segmentectomy 2. This study aimed to present the standardization of laparoscopic segmentectomy 2 with surgical outcomes.This study included seven patients who underwent pure laparoscopic segmentectomy 2 by the Glissonean approach from January 2020 to December 2021. Four of them had hepatocellular carcinoma, two had colorectal liver metastasis, and one had hepatic angiomyolipoma, which was preoperatively diagnosed with hepatocellular carcinoma. In all patients, preoperative three-dimensional (3D) simulation images from dynamic CT were reconstructed using a 3D workstation. The layer between the hepatic parenchyma and the Glissonean pedicle of segment 2 (G2) was dissected to encircle the root of G2. After clamping or ligation of the G2, 2.5 mg of indocyanine green was injected intravenously to identify the boundaries between segments 2 and 3 with a negative staining method under near-infrared light. Parenchymal transection was performed from the caudal side to the cranial side according to the demarcation on the liver surface, and the left hepatic vein was exposed on the cut surface if possible.The mean operative time for all patients was 281 min. The mean blood loss was 37 mL, and no transfusion was necessary. Estimated liver resection volumes significantly correlated with actual liver resection volumes (r = 0.61, P = 0.035). After the operation, one patient presented with asymptomatic deep venous and pulmonary thrombosis, which was treated with anticoagulant therapy. The mean length of hospital stay was 8.9 days.Laparoscopic segmentectomy 2 by the Glissonean approach is a feasible and safe procedure with the preservation of the nontumor-bearing segment 3 for liver tumors in segment 2.

Sorafenib was previously considered a first-line treatment for hepatocellular carcinoma (HCC) patients with macroscopic portal vein tumor thrombus (PVTT). This case-matched analysis was performed to evaluate the best first-line treatment for HCC in patients with macroscopic PVTT.The HCC patients with Vp2 (PVTT invaded into a second-order portal branch), Vp3 (first-order portal branch), and Vp4 (main trunk or contralateral portal vein) PVTT who underwent hepatectomy and those treated with sorafenib were included. Treatment results were compared between the two modalities for each PVTT category, and a propensity analysis was performed for patients with Vp3 and Vp4 (Vp3/4).The median survival times (MSTs) of patients with Vp2, Vp3, and Vp4 PVTT who underwent hepatectomy were 21.4, 13.6, and 14.9 months, respectively; the MSTs for those with Vp2, Vp3, and Vp4 PVTT who received sorafenib treatment were 6.9, 5.5, and 3.6 months, respectively, with a significant difference. In a propensity-matched cohort of patients with Vp3/4 PVTT (36 patients in each), the MST of patients who underwent hepatectomy (15.1 months) was significantly better than the patients treated with sorafenib (4.5 months).Hepatectomy can be associated with prolonged survival in HCC patients with macroscopic PVTT.

Introduction: Although the relationship between systemic inflammatory responses and prognosis has been known in various cancers, it remains unclear which scores are most valuable for determining the prognosis of extrahepatic cholangiocarcinoma. We aimed to verify the usefulness of various inflammation-based scores as prognostic factors in patients with resected extrahepatic cholangiocarcinoma. Methods: We analyzed consecutive patients undergoing surgical resection for extrahepatic cholangiocarcinoma at our institution between January 2000 and December 2019. The usefulness of the following inflammation-based scores as prognostic factor was investigated: glasgow prognostic score (GPS), modified GPS, neutrophil-to-lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutrition index, C-reactive protein to albumin ratio (CAR), controlling nutritional status (CONUT), and prognostic index. Results: A total of 169 patients were enrolled in this study. Of the nine scores, CAR and CONUT indicated prognostic value. Furthermore, multivariate analysis for overall survival revealed that high CAR (>0.23) was an independent prognostic factor (hazard ratio: 1.816, 95% confidence interval: 1.135–2.906, p = 0.0129), along with lymph node metastasis and curability. There was no difference in tumor staging and short-term outcomes between the low CAR (≤0.23) and high CAR groups. Conclusions: CAR was the most valuable prognostic score in patients with resected extrahepatic cholangiocarcinoma.

BACKGROUND Optimal treatment strategies for advanced hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) remain controversial. Therefore, this study aimed to assess the impact and predictive factors of hepatectomy for HCC with macroscopic PVTT. METHODS This study included 100 patients who presented with intraoperatively confirmed PVTT extending to the first portal branch (Vp3), main portal trunk, or opposite-side portal branch (Vp4) between June 2000 and December 2019. Their postoperative outcomes and predictive factors for survival were evaluated. RESULTS Of the 100 patients, 37 (37%) and 63 (63%) had Vp3 and Vp4 PVTTs, respectively. Moreover, 42 (42%) and 58 (58%) patients underwent R0/1 and R2 hepatectomies, respectively. The median survival time (MST) of all patients with Vp3/4 PVTT was 14.5 months; the 1- and 3-year overall survival rates were 59.6 and 16.8%, respectively. The MSTs of patients with Vp3 and Vp4 PVTTs were 16.1 and 14.3 months, respectively (P = 0.7098). The MSTs of patients who underwent R0/1 and R2 hepatectomies were 14.3 and 14.9 months, respectively (P = 0.3831). All assessed tumor factors (including the Vp status [Vp3 or Vp4], type of resection [R0/1 or R2], intrahepatic maximal tumor size, intrahepatic tumor number, and the existence of extrahepatic metastasis) did not influence the overall survival significantly. CONCLUSIONS Tumor factors, such as the presence of a Vp3/4 PVTT, have a strong impact on survival; however, other multiple tumor factors have a limited impact. Hepatectomy can be an effective treatment option for HCC with Vp3/4 PVTT, and its indications should be considered.

Introduction With the aging of the population in Japan, gallbladder cancer (GBC) in the elderly is increasing. However, the available clinical data are limited, and the optimal treatment is still controversial. The aim of this study was to evaluate the benefit of surgical resection in GBC patients ≥75 years of age. Methods A retrospective single center analysis of patients who had undergone surgical resection for GBC between 2000 and 2019 was carried out. Patients aged ≥75 years (elderly group, n = 24) or Results Both younger and elderly patients exhibited similar clinicopathological characteristics, but comorbidity in the latter was significantly greater, as was the frequency of less invasive surgery. Nonetheless, the incidence of postoperative complications was similar in elderly and younger patients. The proportion of patients receiving adjuvant chemotherapy was lower in the elderly. Overall survival of elderly and younger patients was not significantly different (65.0 vs 62.4% at 5 years, P = .600). In multivariate analysis, residual tumor status but not age was an independent prognostic factor. Discussion This study demonstrated that appropriate surgical treatment of elderly GBC patients was safe and effective, despite their having more comorbidities and lower rates of adjuvant chemotherapy than younger patients.

Atezolizumab plus bevacizumab and lenvatinib are the key drugs in the current systemic chemotherapeutic regimen for hepatocellular carcinoma (HCC). Studies have reported the potential effectiveness of lenvatinib introduction after an atezolizumab plus bevacizumab treatment; however, the therapeutic effectiveness of a lenvatinib rechallenge after an atezolizumab plus bevacizumab treatment remains unclear.Thirteen consecutive patients who were rechallenged with lenvatinib after clinical failure following treatments with lenvatinib and atezolizumab plus bevacizumab were included. A comparative study was conducted on the duration and treatment efficacy of the first and second lenvatinib treatments and on the pre- and post-treatment liver function.The median ratios of the 1-month post-treatment alpha-fetoprotein (AFP) levels to the pretreatment AFP levels were 0.750 and 0.667 for the first and second lenvatinib treatments, respectively, without significant difference (p=0.9327). Meanwhile, the median ratios of the 1-month post-treatment albumin-bilirubin (ALBI) scores to the pretreatment ALBI scores were 1.063 and 0.827 for the first and second lenvatinib treatments, respectively, with significant difference (p=0.015). The median duration of the second lenvatinib treatment was significantly shorter than that of the first lenvatinib treatment [2.8 months (range=0.9-4.7 months) vs. 8.7 months (range=3.1-29.7 months)].Lenvatinib re-administration after atezolizumab plus bevacizumab treatment can act as a double-edged sword, as it exerts an anti-tumor effect while being associated with potential liver function deterioration. However, this treatment sequence can be useful, and requires careful monitoring of the transitions in the liver function and the patient's performance status.

Bile leakage is a major complication after liver transplantation and remains as a significant source of morbidity and mortality. In 2011, the International Study Group of Liver Surgery (ISGLS) defined bile leakage as a drain/serum bilirubin ratio ≥3. However, to our knowledge there is no literature assessing serum and drain bilirubin concentrations after liver transplantation. The aim of this study was to describe the natural postoperative changes in serum and drain fluid bilirubin concentrations in patients after liver transplantation.We included 32 patients who underwent liver transplantation at Kobe University Hospital from January 2007 to December 2020. We enrolled 34 living donors who had no complications as the control group.The recipient serum total/direct bilirubin concentration were higher compared with the donors from postoperative day (POD) 1 to 5 with a statistical difference (P.05). The recipient drain/serum total bilirubin ratio was lower than donors on POD 3 (0.89 ± 0.07 vs 1.53 ± 0.07: P.0001), which was also confirmed by the recipient drain/serum direct bilirubin ratio (0.64 ± 0.10 vs 1.18 ± 0.09: P.0001). On POD 3, the drain fluid volume (647.38 ± 89.47 vs 113.43 ± 86.8 mL: P.001) and serum total bilirubin concentration (6.73 ± 0.61 vs 1.23 ± 0.60 mg/dL: P.001) was higher in the recipients than in donors. Categorized in 2 groups, the higher drain fluid volume and bilirubin concentration recipients showed lower drain/serum total bilirubin ratio compared with the other group (P = .03) CONCLUSION: The drain/serum bilirubin ratio in the transplanted patients could be calculated lower compared with the hepatectomy patients because of high drain fluid volume and hyperbilirubinemia. Great care should be taken when assessing the bile leakage in liver transplant recipients using the ISGLS definition.

Background/aim Few studies have established a definite conclusion regarding the limitation of surgical treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC). Patients and methods A retrospective analysis was performed on 717 consecutive patients who underwent initial hepatectomy for HCC. Results Reductive hepatectomy was performed in 103 patients, with a median survival time (MST) of 18.0 months. Total bilirubin and albumin levels were identified as independent prognostic factors. The predictive score of these factors ranged from 0 to 2. Subsequent local treatment was performed in 91.0, 75.0, and 25.0% of patients who scored 0, 1, and 2, respectively. The MST for patients with a score of 0, 1, and 2 was 20.1, 14.8, and 2.7 months, respectively, with a significant difference. Conclusion Patients with BCLC stage B and C could be properly treated with reductive hepatectomy and subsequent local treatments.

Right-sided ligamentum teres (RSLT) is a rare congenital anomaly in which the fetal umbilical vein is connected to the right paramedian trunk of the portal vein. An 80-year-old woman underwent curative sigmoidectomy for sigmoid cancer 3 years prior to presentation. After 1 year, small solitary liver metastasis was noted in segment 4. Because the patient experienced recurrence of the same lesion after chemotherapy and radiofrequency ablation, she was referred to our hospital. CT revealed an anomaly of the liver with RSLT, classified as an independent posterior branch type. The tumor in the left paramedian section was located in the right umbilical portion (RUP), and BDTT was advanced to the common bile duct. Because the estimated future remnant liver volume was 35.2%, transileocecal portal vein embolization (PVE) for the portal branches from the RUP increased it to 43.5% in 3 weeks. Left trisectionectomy with extrahepatic bile duct resection and hepaticojejunostomy were performed. The patient was discharged on postoperative day 75. We successfully performed a left trisectionectomy after PVE in a patient with RSLT. Understanding the vascular and biliary anomalies of patients with RSLT is essential. When the future remnant liver is small, PVE can be considered for safe hepatectomy.

Purpose: Posthepatectomy liver failure (PHLF) is a major complication of hepatectomy. Although the extent of liver resection and fibrosis stages were previously identified as predictors of the development of PHLF, fibrosis stages were diagnosed using samples from resected livers. We evaluated the association between preoperative/intraoperative liver biopsies and final fibrosis stages.Methods: We included 272 patients who underwent an initial hepatectomy at our facility between January 2014 and December 2018.Results: PHLF occurred in 70 patients (25.7%) and decreased their overall survival (p = 0.0001). Preoperative/intraoperative liver biopsies showed a significant correlation with final fibrosis stages (p < 0.0001). The underestimation rates of preoperative and intraoperative F0/F1/F2 were 16.9% and 28.2%, respectively. Among the preoperative factors, 99mTc-GSA scintigraphy LHL < 0.91 was significantly associated with the resected liver fibrosis stages (hazard ratio [HR], 2.38; 95% confidence interval [CI]: 1.37–4.21; p = 0.0022). The underestimation rates of preoperative F0/F1/F2 with 99mTc-GSA scintigraphy LHL > 0.91 and Conclusions: The fibrosis stages of the resected livers were associated with preoperative and intraoperative liver biopsies. Successful hepatectomies could be performed in accordance with findings from preoperative liver biopsies, 99mTc-GSA scintigraphy, and intraoperative liver biopsies without the incidence of PHLF.

Purpose The aim of this study was to investigate the risk factors for delayed gastric emptying (DGE) and the impact of DGE on postoperative nutritional status after subtotal stomach-preserving pancreatoduodenectomy (SSPPD). The pathophysiology of DGE after SSPPD is still unknown, and the precise impact of DGE on various nutritional markers has been scarcely reported. Methods The risk factors for DGE were analyzed using a database created for a previously reported randomized controlled trial (UMIN000005827). To investigate the impact of DGE, data on patient nutrition were analyzed. Results Data from 196 patients were analyzed. DGE occurred in 30 patients (15.3%). Hand-sewn gastrojejunostomy was found to be significantly associated with DGE (P = 0.005). Serum levels of albumin (3.16 g/dL in patients with DGE versus 3.4 g/dL in patients without DGE) and total cholesterol (125.1 mg/dL in patients with DGE versus 147.2 mg/dL in patients without DGE) in DGE patients were lower at postoperative month (POM) one. There was no statistically significant difference in any of the nutritional parameters at POM three or later. On multivariate analysis, preoperative serum albumin P = 0.002) and DGE (Odds ratio, 2.68; P = 0.043) were significantly associated with decreased serum albumin level (

Background Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation. Methods Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015. Results Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients. Conclusions In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor.

Resecting liver tumors located in Couinaud's segment VII is challenging; the efficacy and safety of laparoscopic liver resection for segment VII lesions compared to open liver resection remain unclear.Medical records of 84 patients who underwent liver resection of segment VII at Kobe University Hospital and Hyogo Cancer Center between 2010 and 2021 were retrospectively analyzed. Surgical outcomes were compared between laparoscopic liver resection and open liver resection groups using propensity matching analysis.Thirty-one and 53 patients underwent laparoscopic liver resection and open liver resection, respectively. After propensity matching, 29 patients were included in each group. The laparoscopic liver resection group had a significantly longer operation time (407 vs. 305 min, P = 0.002), lower blood loss (100 vs. 230 mL, P = 0.004), and higher postoperative alanine aminotransferase levels (436 vs. 252 IU/L, P = 0.008) than the open liver resection group. In patients with liver cirrhosis, the proportion of patients with postoperative liver-specific complications was higher in the laparoscopic liver resection group than in the open liver resection group (57% vs 11%, P = 0.049), although there was no significant difference in postoperative liver-specific complication rates between the groups in patients without liver cirrhosis.For liver resection of segment VII, laparoscopic liver resection led to higher postoperative liver damage than open liver resection. Open liver resection may be better for patients with liver cirrhosis to avoid postoperative liver-specific complications. Laparoscopic liver resection could be an acceptable procedure for patients without liver cirrhosis, with some merits such as less blood loss.

Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan.In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018.Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads.THIS NATIONWIDE SURVEY REVEALED FOR THE FIRST TIME HOW LIVING DONOR LIVER AND KIDNEY: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

Undifferentiated pleomorphic sarcoma(UPS)is a non-epithelial malignant tumor with a high rate of recurrence and metastasis. The frequent metastasis site is lung, lymph node, liver and bone. Pancreatic metastasis is rare. 71-year-old woman whose course after right foot UPS resection had been followed up at our hospital. But multiple bone and muscle metastasis occurred 1 year after operation. She had resection or radiation for the recurrence. 3 years after the first operation, PET-CT and EUS-FNA revealed pancreatic tail metastasis. The tumor grew up in 6 months, so we performed laparoscopic distal pancreatectomy. The patient recovered uneventfully and was discharged on post-operative day 14. Currently 5 years and 6 months have passed since the first surgery and she is alive. Function-preserving and minimally invasive surgery for UPS pancreatic metastasis is considered to be essential.

A woman in her 80s was diagnosed with pancreatic tail cancer by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We performed laparoscopic distal pancreatectomy followed by adjuvant chemotherapy with S-1 for 6 months. One year after surgery, contrast-enhanced computed tomography revealed a 15 mm mass in the posterior wall of the gastric body. EUS showed a hypoechoic mass in the muscular layer in the gastric wall, which was diagnosed as adenocarcinoma by FNA. We diagnosed gastric wall recurrence due to needle tract seeding(NTS)following EUS-FNA and performed partial gastrectomy. Histopathological diagnosis was gastric wall recurrence of pancreatic cancer. Since NTS following EUS-FNA can be proven only by the presence of gastric wall recurrence after surgery for pancreatic body or tail cancer, the actual risk of NTS including peritoneal dissemination is not clear and may have been underestimated. In case of resectable pancreatic body or tail cancer, indication for EUS-FNA should be carefully considered.

A 73-year-old woman underwent a subtotal stomach-preserving pancreaticoduodenectomy, wedge resection of the portal vein, and partial resection of the transverse colon for pancreatic cancer at the age of 71. After 18 months, a computed tomography image showed an 8 mm tumor in the ascending jejunal mesentery. Six months later, the tumor grew to 20 mm and had an increased FDG uptake. The tumor was diagnosed as metastasis of pancreatic cancer to the ascending jejunal mesentery. Since no metastasis was found in the other organs, resection was performed. The pathological results showed adenocarcinoma with proximal lymph node metastasis. The patient was diagnosed with ascending jejunal mesentery metastasis of pancreatic cancer. The patient has remained healthy without recurrent disease 1 year 6 months after the resection. Ascending jejunal mesentery metastasis of pancreatic cancer is a type of distant metastasis. In the absence of metastasis to other organs, it is tolerable and radical resection is possible.

Stapling is the standard method for pancreatic transection during laparoscopic distal pancreatectomy. Although most surgeons use a 60 mm cartridge stapler, space limitations created by laparoscopic surgery make the instrument difficult to handle, especially during pancreatic transection at the neck. Therefore, we currently use a 45 mm cartridge stapler for laparoscopic pancreatic transection at the neck. Between October 2019 and December 2020, we performed pancreatic transection using a 45 mm cartridge stapler in 27 patients. Fifteen patients experienced biochemical leakage, but no patients developed clinically relevant pancreatic fistula. The compactness of the 45 mm cartridge has several benefits: (1) less space is required for flexing, opening, and closing the device; (2) it enables easy insertion of the lower jaw behind the pancreas, even if the dissected space behind the pancreas is narrow; (3) less obstruction of the surgeons' view prevents accidental injury to the surrounding tissues and vessels. These benefits may enable safe pancreatic transection.

Background Hepatocellular carcinoma (HCC) with major portal vein tumor thrombus (Vp4 PVTT) is an extremely advanced tumor with limited treatment options. Systemic chemotherapy is the only recommended treatment option, and atezolizumab plus bevacizumab has recently emerged as a first-line treatment option. Case presentation We describe the case of an 82-year-old man with unresectable advanced HCC with Vp4 PVTT who achieved a significant response to atezolizumab plus bevacizumab treatment. A single administration of atezolizumab plus bevacizumab ensured significant anti-tumor effects (regression in the tumor size and PVTT, portal vein recanalization, and serum alfa-fetoprotein levels decreased from 90,770 to 89 ng/mL). The patient continued with atezolizumab monotherapy, and after nine consecutive regimens, there was no apparent sign of residual tumor. Conclusions This case demonstrates the powerful anti-tumor effect of atezolizumab plus bevacizumab treatment for advanced HCC with Vp4 PVTT, suggesting that these agents can be a promising treatment option for such refractory tumors.

The prognosis of hepatocellular carcinoma (HCC) presenting with inferior vena cava tumor thrombus (IVCTT) is extremely poor. The aim of this study was to reveal the postoperative course and to identify patients who have survived surgical hepatectomy among HCC patients with IVCTT. Between January 2006 and December 2018, 643 patients underwent surgical hepatectomy for HCC at Kobe University Hospital. Among them, 20 patients were categorized as Vv3 according to the Japanese staging system. We retrospectively collected detailed data on these patients. The statistical, clinical, and pathological data were recorded prospectively and analyzed retrospectively. The median survival time was 9.8 months. Among all patients, 11 (55%) achieved R0 resection, and only two survivors were from this group. The number of tumors (solitary vs. multiple; p=0.050) and pathological Vp (pVp0 vs. other; p=0.009) were identified as risk factors for overall survival in the univariate analysis. In the multivariate analysis, pathological Vp (pVp0 vs. other; p=0.037) was identified as a significant prognostic factor for survival. Pathological Vp affected overall survival among IVCTT patients; the median survival time was 53.7 months with pVp0, 10.2 months with pVp1, and 8.8 months with pVp2–4 (p=0.035). For patients with IVCTT, surgical hepatectomy should be indicated only for those who do not have portal vein invasion and could achieve R0 resection.

Background/aim While there is increasing evidence supporting the role of several first- and second-line treatment regimens for advanced hepatocellular carcinomas (HCC), the clinical relevance of rechallenge treatment with previously administered drugs, however, remains to be explored. Patients and methods Five consecutive patients with advanced HCC who received lenvatinib rechallenge treatment after ramucirumab were assessed. Results All patients were clinically diagnosed with failure after ramucirumab treatment, and the frequencies of ramucirumab administration before lenvatinib re-administration ranged from 3 to 11. The alfa-fetoprotein level in four of five patients decreased 1 month after the lenvatinib rechallenge. Radiological findings via the modified Response Evaluation Criteria in Solid Tumors showed stable diseases in four patients and a partial response in one. Conclusion Rechallenge treatment with lenvatinib after ramucirumab can be effective, and may be a treatment option for HCC in cases wherein the disease progressed after an initial response to lenvatinib treatment.

This study aimed to evaluate the clinical relevance of hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stages B and C advanced hepatocellular carcinoma (HCC). A total of 314 patients (149 and 165 BCLC stages B and C, respectively) who underwent hepatectomy were included. Complete hepatectomy (without residual tumors after hepatectomy) and reductive hepatectomy (apparent residual tumors after hepatectomy) were performed for 212 and 102 patients, respectively. Short-term operative and postoperative outcomes, as well as long-term outcomes, were evaluated. The median survival times of patients with stage B disease undergoing complete hepatectomy and reductive hepatectomy were 48.9 and 20.1 months, respectively (p = 0.0075), whereas those of patients with stage C disease were 19.5 and 17.6 months, respectively (p = 0.0140). The 3-year overall survival rates of patients with stage B disease undergoing reductive hepatectomy with and without subsequent local treatments after surgery were 47.5% and 0%, respectively, whereas those of patients with stage C diseases were 18.6% and 0%, respectively. Survival benefits are obvious for both BCLC stages B and C HCC when complete hepatectomy can be performed safely. Reductive hepatectomy is also acceptable for BCLC stages B and C when subsequent local treatment for remnant liver tumors can be performed safely after reductive hepatectomy. Without subsequent local treatment, reductive hepatectomy has little clinical relevance. Thus, a cautious approach to patient selection is required for this aggressive strategy.

Purpose We investigated the status of deceased organ donation and transplantation through a questionnaire distributed to transplant centers in Japan during the COVID-19 pandemic. Methods The questionnaire was distributed electronically to 206 transplant centers for heart (n = 11), lung (n = 10), liver (n = 25), kidney (n = 130), pancreas (n = 18), and small intestine (n = 12) transplantation. Organ donations and organ transplantation data were extracted from the Japan Organ Transplant Network website. Results We received questionnaire responses from 177 centers (response rate, 86%). In 2020, the number of brain-dead donors (BDDs) decreased to 68 (69% of the year-on-year average) and the number of donors after cardiac death (DCDs) decreased to 9 (32% of the year-on-year average). Eighty-five (48%) transplant centers (heart, n = 0; lung, n = 0; liver, n = 4; kidney, n = 78; pancreas, n = 22; and small intestine, n = 0) suspended transplant surgeries in response to the COVID-19 pandemic. Consequently, the number of organ transplantations from deceased donors was significantly lower in 2020 than in 2019. Conclusion Although the COVID-19 pandemic has had less impact in Japan than in other countries, it has affected transplantation activity significantly, suspending transplantation surgeries in 48% of the transplantation centers, including 78% of the kidney transplantation centers, and reducing the number of organ donations to 61% of the year-on-year average.

BACKGROUND Although liver transplantation is widely accepted as the therapeutic strategy for end-stage liver failure, complication of hepatic venous outflow obstruction remains lethal. Currently, ensuring a single wide orifice in both the graft and recipient inferior vena cava has been proposed to avoid hepatic venous outflow obstruction with no theoretical concept. METHODS We herein report a standardization technique for the reconstruction of the hepatic vein based on the causal analysis. RESULTS During the put-in process, the graft must be positioned in contact with the recipient diaphragm and slightly pushed to the cranial direction to simulate the state after abdominal closure. Because there is no extra space between the graft and diaphragm, the graft could not rotate about the anastomotic site of the inferior vena cava toward the diaphragm after abdominal closure as the intestinal pressure increases, and accordingly hepatic venous outflow obstruction does not develop. CONCLUSIONS With this concept, all transplant surgeons can successfully and easily perform hepatic vein reconstruction without total clamping of the inferior vena cava and without outflow block.

This study aims to validate Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) and confirm the feasibility of performing transplantation.We included 60 patients with acute liver injury. Demographic and clinical features were retrospectively collected, and the primary outcome was compared among 4 types: acute liver failure (ALF) with hepatic coma (n = 23), ALF without hepatic coma (n = 12), acute liver injury (n = 20), and ACLF (n = 5). Moreover, 80 transplanted patients were enrolled to compare the difficulty of transplantation between ALF (n = 8) vs non-ALF (n = 72) patients.Seven patients in the ALF with hepatic coma group and 1 patient in the ACLF with hepatic coma group were transplanted. Ten patients who could not be registered for transplantation died. In univariate analysis, liver failure type (P.0001), total bilirubin level (P = .05), and prothrombin time internationalized ratio (P.0001) were associated with patient survival. In multivariate analysis, liver failure type was associated with patient survival (P.0001). The respective 1-, 3-, and 5-year patient survival rates were 45.9%, 45.9%, and 45.9% for ALF patients with hepatic coma; 100.0%, 100.0%, and 100.0% for ALF patients without hepatic coma and acute liver injury; and 80.0%, 80.0%, and 80.0% for ACLF patients (P.0001). Chronic liver disease did not affect operation time (P = .46) and bleeding volume (P = .49).Patients diagnosed with ACLF via Japanese criteria presented significantly higher survival rates than ALF patients with hepatic coma.

We compared surgical outcomes, with a focus on tumor characteristics, of laparoscopic repeat hepatectomy (LRH) and open repeat hepatectomy (ORH) to identify recurrent hepatocellular carcinoma (HCC) cases where the LRH procedure would be more favorable than ORH. Eighty-one HCC patients who underwent repeat hepatectomy in our hospital from 2008 to 2019 were retrospectively analyzed in this study. Of these patients, 30 and 51 patients underwent LRH and ORH, respectively. We analyzed surgical outcomes of LRH and ORH, focusing on tumor characteristics such as tumor size, location, distance from major vessels, and contralateral or ipsilateral tumor recurrence to determine what factors could affect surgical outcomes. Subsequently, using a propensity-matched cohort, we compared the impact of those factors on LRH and ORH outcomes. In the entire cohort, the LRH operation time was significantly shorter in contralateral recurrent HCC cases than in ipsilateral recurrent HCC cases (252 vs. 398 min, P = 0.008); however, such a difference was not observed in the ORH operation time. We subsequently compared the surgical outcomes, in terms of the location of tumor recurrence, between the LRH and ORH groups in a propensity-matched cohort. In total, 23 patients were included in each of these groups. We found that the LRH procedure had significantly shorter operative time than the ORH procedure in the contralateral recurrent HCC cases (253 vs. 391 min, P = 0.018); however, we did not observe such a difference in the ipsilateral recurrent HCC cases (372 vs. 333 min, P = 0.669). LRH had lower blood loss, similar postoperative complications and shorter hospital stay than ORH in both contralateral and ipsilateral recurrent HCC cases. LRH is likely considered a more favorable approach than ORH in treating patients with contralateral recurrent HCC.

Although surgical resection is the first-line treatment for biliary tract cancer(BTC), elderly patients often have underlying diseases and decreased cardiopulmonary function that place them at a high risk of undergoing surgery. We examined the safety and efficacy of surgical resection in elderly BTC patients. Among the BTC cases that underwent surgical resection at Kobe University Hospital from 2009 to 2015, the safety and prognosis ofthose aged 75 years or older(Group 1)were compared to those younger than 75 years(Group 2)at the time ofsurgery. Fifty-two patients with perihilar cholangiocarcinoma( Bp), 29 patients with intrahepatic cholangiocarcinoma(ICC), and 40 patients with ampulla ofVater cancer(AV) were included. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲor above, while surgery-related death was more common in Bp and ICC ofGroup 1. The median survival ofGroup 1 following hepatectomy for Bp and ICC(22 months)was significantly shorter than that of Group 2(40 months)(p=0.023). There was no significant difference in overall survival of Group 1 and Group 2 patients with AV(p=0.094). Surgical resection for BP and ICC for elderly patients has a higher risk of hepatectomy; therefore, precise assessment of oncologic and patient risk factors should be performed. As we can expect to achieve similar prognoses between non-elderly and elderly patients with AV, aggressive treatments should be considered for elderly patients with AV.

Optimal management for liver metastases from colorectal mucinous adenocarcinoma is still controversial. Here, we report such a case of liver metastases that developed twice with 10-year intervals after curative resection. An 84-year-old man had undergone a radical left hemicolectomy for descending colon cancer at age 63 years. The histopathologic diagnosis was mucinous adenocarcinoma. Ten years later, he was found to have a cystic tumor in liver and underwent partial hepatectomy of segment 5. Moreover, 10 years after that hepatic resection, computed tomography showed a low-density tumor with calcification in remnant liver, and partial hepatectomy of segment 8 was performed. Histopathologic and immunohistochemical findings of each liver tumor indicated metastasis from primary colon mucinous adenocarcinoma. It is rare for colorectal mucinous adenocarcinoma to recur twice after long intervals of 10 years. However, in a patient with a history of colorectal mucinous adenocarcinoma, possibility of recurrence more than 10 years after curative surgery also must be kept in mind. Long-term clinical follow-up after curative surgery for primary colon cancer or liver metastases may be necessary to detect early signs of recurrence of colorectal mucinous adenocarcinoma.

Background: This study evaluated the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases who can undergo hepatectomy. Methods: A total of 32 patients who underwent hepatectomy for HCC with extrahepatic metastases, including lymph node and/or distant metastases were recruited for this study. Results: Fourteen patients had lymph node metastasis only, 16 had distant metastasis only, and 2 had both metastasis types during preoperative diagnosis. The 3-year overall survival (OS) rate of all patients was 17.9%, and the median survival time (MST) was 11.8 months. Univariate analysis revealed that intrahepatic maximal tumor size, intrahepatic tumor number, and intrahepatic tumor control after hepatectomy were significant factors influencing OS (p < 0.05). Multivariate analysis revealed that independent risk factors for OS were intrahepatic maximal tumor size and intrahepatic tumor number (p < 0.05). The MST and 3-year OS rate of patients with maximal tumor size Conclusions: Hepatectomy is not recommended for HCC patients with extrahepatic metastasis with ≥3 intrahepatic tumors, even when all intrahepatic tumors can be eliminated via hepatectomy. Aggressive surgery may be justified for HCC patients with ≤2 intrahepatic tumors and maximal tumor size

Background The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). Methods The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients. Results Of the study subjects, 37 patients had Child–Pugh class A (CPA) liver function, and 14 patients had Child–Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1–2 months, or 2–3 months (p = 0.2368, 0.9368, and 0.9293). Conclusion The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment.

Background The albumin-bilirubin (ALBI) grade, stratified from the ALBI score, may have prognostic value in patients with hepatocellular carcinoma. We aim to evaluate the prognostic abilities of the ALBI score/grade among living-donor liver transplantation patients. Methods We retrospectively collected data of 81 patients who underwent living-donor liver transplant at Kobe University Hospital between June 2000 and October 2018. The efficacy of the ALBI score/grade as a prognostic factor was assessed and compared with that of the well-established Model for End-Stage Liver Disease (MELD) score. Main findings Multivariate analysis indicated that recipient age (P = .003), donor age (P = .003), ALBI score ≥ -1.28 (P = .002), and ALBI grade III (P = .004) were independently associated with post-transplant survival. A high MELD score was not associated with post-transplant survival in univariate or multivariate analyses. Although there was no significant difference in the overall survival rate relative to recipient and donor age, ALBI score/grade was significantly associated with the 1- and 5-year survival rates (P = .023, P = .005). ALBI scores specifically detected fatal complications of post-transplant graft dysfunction (P = .031) and infection (P = .020). Conclusion ALBI score/grade predicted patient survival more precisely than the MELD score did, suggesting that it is a more useful prognostic factor compared to the MELD score in living-donor liver transplantation cases.

IntroductionIn-vivo fluorescence imaging techniques using indocyanine green (ICG) to identify liver tumours and hepatic segment boundaries have been recently developed. The purpose of this study is to evaluate the efficacy of fusion ICG-fluorescence imaging for navigation during hepatectomy.Methods and analysisThis will be an exploratory single-arm clinical trial; patients with liver tumours will undergo hepatectomy using the ICG-fluorescence imaging system. In total, 110 patients with liver tumours scheduled for elective hepatectomy will be included in this study. Preoperatively, ICG will be intravenously injected at a dose of 0.5 mg/kg body weight within 2 days. To detect liver tumours intraoperatively, the hepatic surface will be initially observed using the ICG-fluorescence imaging system. After identifying and clamping the portal pedicle corresponding to the hepatic segments, including the liver tumours to be resected, additional ICG will be injected intravenously at a dose of 0.5 mg/kg body weight to identify the boundaries of the hepatic segments. The primary outcome measure will be the success or failure of the ICG-fluorescence imaging system in identifying hepatic segments. The secondary outcomes will be the success or failure in identifying liver tumours, liver function indicators, operative time, blood loss, rate of postoperative complications and recurrence-free survival. The findings obtained through this study are expected to help to establish the utility of ICG-fluorescence imaging systems, and therefore contribute to prognostic outcome improvements in patients undergoing hepatectomy for various causes.Ethics and disseminationThe protocol has been approved by the Kobe University Clinical Research Ethical Committee. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberUMIN000031054 and jRCT1051180070

We assessed the predictive value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients who underwent a two-stage treatment combining reductive surgery and percutaneous isolated hepatic perfusion for multiple hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Forty-two patients underwent the two-stage treatment between January 2000 and December 2014 at Kobe University Hospital (Hyogo, Japan). The NLR was calculated from lymphocyte and neutrophil counts in the preoperative routine blood test. Clinical data and overall survival were compared statistically and multivariate analysis was done to identify prognostic factors.The median survival of patients with a preoperative NLR 2.3 was 14.9 months (n = 13), whereas that of patients with a preoperative NLR ≤ 2.3 was 26.1 months (n = 29; P = 0.022). A preoperative NLR 2.3 was an independent prognostic factor in patients with multiple HCC with PVTT [hazard ratio (HR) 2.329; 95 % confidence interval (CI) 1.058-5.667; P = 0.036].Based on the results of this study, an elevated preoperative NLR is an independent predictive risk factor for patients undergoing two-stage treatment for multiple HCC with PVTT.

Although several publications have reported donor morbidities, deterioration of liver function, which may cause posthepatectomy liver failure (PHLF), was not assessed specifically. The incidence of PHLF proposed by the International Study Group of Liver Surgery (ISGLS-PHLF) was analyzed among 257 living donors. ISGLS-PHLF was defined by an increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5. ISGLS-PHLF was identified in 21 donors (8 %), of which 18 (85.7 %) were grade A, 2 (9.5 %) were grade B, and 1 (4.8 %) was grade C. The average hospital stay without ISGLS-PHLF was 15 ± 1 days, which extended along with increasing grades (p = 0.03). In univariate analysis, right hepatectomy was significantly associated with the incidence of ISGLS-PHLF (p = 0.02), and right hepatectomy (p = 0.002) and operation time (p = 0.01) in multivariate analysis. Of 176 right lobe donors, 19 (10.8 %) developed ISGLS-PHLF, of which 16 (84.2 %) were grade A, 2 (10.5 %) were grade B, and 1 (5.3 %) was grade C. Operation time was significantly associated with the incidence of ISGLS-PHLF in univariate (p = 0.002) and multivariate (p = 0.003) analyses. Right lobe donation surgery is associated with a higher incidence of ISGLS-PHLF.

A 44-year-old woman underwent surgical resection and received preoperative and postoperative chemotherapy for conventional osteosarcoma in the right fibular head. Three years later, follow-up PET-CT revealed accumulation ofFDG in the tail ofthe pancreas. Contrast-enhanced computed tomography showed a 13mm well-circumscribed hypovascular tumor. EUS showed a heterogeneous solid tumor, which was diagnosed as metastasis ofosteosarcoma to the pancreas. Laparoscopic spleen preserving distal pancreatectomy(LAP-SPDP)was performed. Pathologically, the tumor was diagnosed as metastasis ofconventional osteosarcoma to the pancreas. Cells from pancreas islet tissue were detected in the tumor, suggesting invasion ofthe tumor into the pancreatic body and surrounding adipose tissue. Although postoperative chemotherapy was administered, lung metastasis was detected 1.1 years after surgery. Laparoscopic partial resection of the lung metastasis was performed, and the patient is still alive. Metastasis ofosteosarcoma to the pancreas is rare, and there is no report oflaparoscopic approach as a treatment. Herein, we report a case with several references.

Pharmacologic agents to enhance liver regeneration after injury would have wide therapeutic application. Based on previous work suggesting inhibition of bone morphogenetic protein (BMP) signaling stimulates liver regeneration, we tested known and novel BMP inhibitors for their ability to accelerate regeneration in a partial hepatectomy (PH) model. Compounds were produced based on the 3,6-disubstituted pyrazolo[1,5-a] pyrimidine core of the BMP antagonist dorsomorphin and evaluated for their ability to inhibit BMP signaling and enhance liver regeneration. Antagonists of the BMP receptor activin receptor–like kinase 3 (ALK3), including LDN-193189 (LDN; 4-[6-[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline), DMH2 (4-(2-(4-(3-(quinolin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenoxy)ethyl)morpholine; VU0364849), and the novel compound VU0465350 (7-(4-isopropoxyphenyl)-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine; VU5350), blocked SMAD phosphorylation in vitro and in vivo, and enhanced liver regeneration after PH. In contrast, an antagonist of the BMP receptor ALK2, VU0469381 (5-(6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinolone; 1LWY), did not affect liver regeneration. LDN did not affect liver synthetic or metabolic function. Mechanistically, LDN increased serum interleukin-6 levels and signal transducer and activator of transcription 3 phosphorylation in the liver, and modulated other factors known to be important for liver regeneration, including suppressor of cytokine signaling 3 and p53. These findings suggest that inhibition of ALK3 may be part of a therapeutic strategy for treating human liver disease.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication after transplantation. A living donor liver transplantation was performed on a 31-year-old man for fulminant hepatitis. He again developed liver dysfunction after 7 months. He was diagnosed as having acute cellular rejection and the steroid pulse therapy introduced resulted in little improvement. He gradually developed a high fever and right axillary lymphadenopathy appeared. Chest computed tomography (CT) was performed revealing small lung nodules and axillary lymphadenopathy. Because his serological status for Epstein-Barr virus was positive, PTLD was highly suspected and immunosuppression treatment was withdrawn with little improvement. One week later, he developed tachycardia. Chest CT was re-performed revealing an infiltration to the left cardiac chamber. For diagnosis, axillary lymph node biopsy was performed and during the procedure, he developed ventricular tachycardia (VT). Immunohistological staining revealed PTLD of T lymphocytes, and chemotherapy was introduced on the same day he developed VT. After two cycles of tetrahydropyranyl, adriamycin, cyclophosphamide, vincristine, prednisolone and etoposide treatment, he completely recovered. This is a first case report of severe PTLD with VT, and our case implies the feasibility of chemotherapy after the appearance of dissemination symptoms.

Recent progress in medical technology, perioperative management, and surgical technique has contributed greatly to the safety of hepatobiliary surgery. In particular, imaging techniques, including intraoperative imaging, have played a major role in advancing the success of these operations. Precise assessment of biliary anatomy before and during surgery reduces biliary complications. More than 42% of the population is reported to have anatomical variations of the biliary tree. If a biliary anatomical variation is suspected before surgery, confirmatory intraoperative cholangiography (IOC) is recommended. Using radiography and iodinated contrast medium, IOC was first reported by Mirizzi in 1937 and has been widely used to define the biliary tree in surgery for benign and malignant diseases. However, radiographic IOC has several drawbacks; it exposes patients and medical staff to radiation, it requires a large C-arm machine for fluoroscopy and an attendant to operate it, and it requires special techniques to generate 3-dimensional (3D) images. Intraoperative ultrasonography, specifically, contrast-enhanced intraoperative ultrasonic cholangiography (CE-IOUSC), can address these issues. Intraoperative ultrasonography has become an essential tool for the identification of intrahepatic vessels, tumor location, and definition of surgical margins for safe and effective hepatic surgery. Its diagnostic accuracy has been enhanced by the introduction of intravascular ultrasound contrast agents. However, it is still limited in visualization of nondilated bile ducts.

IntroductionMultimodal treatment prolongs the survival of patients with biliary tract cancer (BTC). However, the chemotherapy choices for this disease are few, and completing each chemotherapy session is important. Adjuvant chemotherapy has been attempted for BTC, but has only had a 75% completion rate. Body weight loss and cholangitis are reasons for the interruption of chemotherapy. Previous reports suggested that nutritional intervention with omega-3 fatty acids maintained body weight and improved the completion rate for chemotherapy. Moreover, omega-3 fatty acids have an anti-inflammatory effect. Therefore, we theorised that omega-3 fatty acids would improve the completion rate of adjuvant chemotherapy in patients with BTC. The aim of this study is thus to evaluate the effectiveness of omega-3 fatty acids for patients planning adjuvant chemotherapy for BTC.Method and analysisThis study is a single-centre, open-label, single-arm, historically controlled study with a planned enrolment of 55 participants. Protocol treatment consists of four courses of S-1 adjuvant chemotherapy and an oral omega-3 fatty acid pharmaceutic adjuvant (LOTRIGA 2 g (Takeda Pharmaceutical Co.)), which includes 2 g of omega-3 fatty acids from day 1 until day 168 of the treatment period. The primary endpoint is the completion rate of four total courses of S-1. Secondary endpoints are postoperative cholangitis, time to recurrence or distant metastasis, changes in nutritional index, changes in the lymphocyte blast transformation test induced by phytohaemagglutinin, and concanavalin A and diamine oxidase serum activity during adjuvant chemotherapy. All adverse events will be evaluated.Ethics and disseminationThis protocol was approved by the Institutional Review Board of Kobe University Hospital. The findings from this study will be presented at national and international conferences and published in peer-reviewed journals.Trial registration numberUMIN000031247.

Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients. We retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. The median follow-up period after hepatectomy was 35.2 months. Thirty-nine (18.6 %) patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at 1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and 45.1/57.8 %, respectively (P = 0.002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and 15.7/20.3 %, respectively (P = 0.003). Multivariate analysis revealed that PHLF was significantly associated with both OS (P = 0.047) and RFS (P = 0.019). Extent of resection (P

Tight junctions (TJs) and adherens junctions (AJs) form an apical junctional complex at the apical side of the lateral membranes of epithelial cells, in which TJs are aligned at the apical side of AJs. Many cell adhesion molecules (CAMs) and cell polarity molecules (CPMs) cooperatively regulate the formation of the apical junctional complex, but the mechanism for the alignment of TJs at the apical side of AJs is not fully understood. We developed a cellular system with which epithelial-like TJs and AJs were reconstituted in fibroblasts and analyzed the cooperative roles of CAMs and CPMs. We exogenously expressed various combinations of CAMs and CPMs in fibroblasts that express negligible amounts of these molecules endogenously. In these cells, the nectin-based cell-cell adhesion was formed at the apical side of the junctional adhesion molecule (JAM)-based cell-cell adhesion, and cadherin and claudin were recruited to the nectin-3- and JAM-based cell-cell adhesion sites to form AJ-like and TJ-like domains, respectively. This inversed alignment of the AJ-like and TJ-like domains was reversed by complementary expression of CPMs Par-3, atypical protein kinase C, Par-6, Crb3, Pals1 and Patj. We describe the cooperative roles of these CAMs and CPMs in the apico-basal alignment of TJs and AJs in epithelial cells.

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P<0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.

Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT. Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types. The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively. BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.

Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are frequently used as tumor markers in hepatocellular carcinoma (HCC). The authors hypothesized different patient populations with varying tumor sizes would influence the predictive power of tumor markers for survival in HCC patients. The authors investigated the influence of tumor size on predictive powers of AFP and DCP. 181 patients underwent hepatectomy for HCC from 2003 to 2008 at Kobe University Hospital. Tumor markers were measured before and at 1 month post-hepatectomy. The Cox proportional-hazards model revealed that preoperative serum AFP was associated with survival; its effects depended on tumor size. Hazard ratios (HRs) for preoperative AFP were maximum for medium-sized HCC, and for DCP, HRs were maximum in small-sized tumors. Post-hepatectomy, both tumor markers were associated with survival, revealing significant interactions with tumor size. HRs for postoperative AFP were greater than 1 for relatively wide range tumors (3-11 cm). HRs for postoperative DCP increased with tumor size, with a strong prognostic predictive power for tumors5 cm. The predictive power of serum tumor markers varied by tumor size in HCC patients. By selecting the appropriate tumor marker, its predictive power can be improved.