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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

Aim This study aimed to evaluate the indications of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma from the viewpoint of its difficulty. Methods One hundred and one patients who underwent LRLR and 59 patients who underwent open repeat liver resection (ORLR) were included. The difficulty was classified according to the preoperative predictive factors for difficult LRLR, including an open approach during previous liver resection, history of two or more previous liver resections, history of previous major liver resection, tumor near the resected site of the previous liver resection, and intermediate or high difficulty with the difficulty scoring system. We compared the surgical outcomes between the LRLR and ORLR groups based on the difficulty class (low‐ or intermediate difficiulty class, 0 to 3 predictive factors; high difficiulty class, 4 or 5 factors). Results In the low‐ or intermediate difficiulty class, intraoperative blood loss and the proportion of patients with postoperative complications were significantly lower in LRLR than in ORLR, and the duration of the postoperative hospital stay was significantly shorter in LRLR than in ORLR. In the high difficiulty class, total operative time and operative time before starting hepatic parenchymal resection were significantly longer in LRLR than in ORLR, and there were no significant differences in other surgical outcomes between the two groups. Conclusion LRLR is recommended for patients in the low or intermediate difficulty class. However, LRLR does not have an advantage with longer operative time for patients in the high difficulty class compared with ORLR., Laparoscopic repeat liver resection (LRLR) is recommended for patients in our suggested low or intermediate difficulty class. On the other hands, LRLR does not have an advantage with longer operative time for patients in the high difficulty class, compared with open repeat liver resection.

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. 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). 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). 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.

Background Extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection. Methods The participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping. Results Extrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively. Conclusion We have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.

We aimed to develop the deep learning (DL) predictive model for postoperative early recurrence (within 2 years) of hepatocellular carcinoma (HCC) based on contrast-enhanced computed tomography (CECT) imaging. This study included 543 patients who underwent initial hepatectomy for HCC and were randomly classified into training, validation, and test datasets at a ratio of 8:1:1. Several clinical variables and arterial CECT images were used to create predictive models for early recurrence. Artificial intelligence models were implemented using convolutional neural networks and multilayer perceptron as a classifier. Furthermore, the Youden index was used to discriminate between high- and low-risk groups. The importance values of each explanatory variable for early recurrence were calculated using permutation importance. The DL predictive model for postoperative early recurrence was developed with the area under the curve values of 0.71 (test datasets) and 0.73 (validation datasets). Postoperative early recurrence incidences in the high- and low-risk groups were 73% and 30%, respectively (p = 0.0057). Permutation importance demonstrated that among the explanatory variables, the variable with the highest importance value was CECT imaging analysis. We developed a DL model to predict postoperative early HCC recurrence. DL-based analysis is effective for determining the treatment strategies in patients with HCC.

研究グループは、肝細胞癌の腫瘍分化度による予後不良リスクは腫瘍サイズとともに増大することを明らかにしました。近年国内でも増加している生活習慣病などが原因となって発症する肝細胞癌ですが、肝細胞癌における腫瘍分化度と予後との関連性は一定の見解が得られておらず、欧州肝臓学会のガイドラインでも「結論に至っていない」と示されています。今回1,107例の肝細胞癌肝切除症例を対象に検討したところ、低分化型は術後予後不良因子であり、腫瘍サイズ5cmまでは予後不良リスクが急激に上昇することが分かりました。腫瘍サイズを, Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). / Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size....

Background Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. Methods The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P. Results In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively. Conclusions Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors. .

Background Occupational cholangiocarcinoma (CCA) was first described in patients who were working at a printing company in Osaka, Japan. Recently, the therapeutic efficacy and safety of a PD1 inhibitor nivolumab are being evaluated in patients with occupational CCA in an investigator-initiated clinical trial. The therapeutic effects of immune checkpoint inhibitors are closely associated with immune cells. Methods Immunohistochemical analysis was performed to characterize immune cells in the tumor microenvironment of occupational CCA. The status of mismatch repair (MMR)/microsatellite instability (MSI) was also examined. Results The tumor stroma of occupational CCA was characterized by abundant infiltration of immune cells expressing CD3, CD4, CD8, CD163, FOXP3, and granzyme B. Additionally, lymphocytes expressing immune checkpoint receptors, such as PD1, CTLA4, LAG3, TIM3, and TIGIT, were frequently infiltrated. The loss of immunohistochemical expression of the MMR proteins (MLH1, MSH2, PMS2, and MSH6) was not observed in cases of occupational CCA, and MSI was not detected. Conclusions The tumor microenvironment of occupational CCA had features of immunosuppression, and the occurrence of T-cell dysfunction or exhaustion was suggested. The results provide supportive evidence for the efficacy of immune checkpoint inhibitor therapy for this disease.

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).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.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).Compared with OLR, LLR for HCC might reduce postoperative infections, including organ/space SSI and RI.

The incidence of postoperative adhesions is directly correlated with the difficulty level of repeat hepatectomies. However, the incidence, location, and severity of postoperative adhesions in relation to hepatectomy-related operative procedures are yet unclear.First hepatectomy-induced hard dense adhesions were evaluated from the surgical records and/or videos of 168 patients who underwent second hepatectomies.The incidence of postoperative hard dense adhesions around the liver was significantly associated with locations, such as the hepatic cut surface, dissected areas around the liver, and peri-incision peritoneum, and hepatectomy-related operative procedures, such as Pringle maneuver and cholecystectomy. The incidence of hard dense adhesions after dissection was higher around the right liver than in the left infraphrenic space. Further, the incidence of hard dense adhesions around the hepatoduodenal ligament or Morison pouch was greater than 30% even in patients who did not undergo Pringle maneuver, cholecystectomy, or hepatorenal ligament dissection. Although the incidence of hard dense adhesions of the peritoneum around the incision was higher after open hepatectomy than after laparoscopic hepatectomy, adhesion barrier use reduced the incidence of such adhesions in patients after open hepatectomy.Hepatectomy-related operative procedures such as peri-hepatic dissection, Pringle maneuver and cholecystectomy are directly associated with postoperative hard dense adhesions. However, the incidence of postoperative hard dense adhesions around the hepatoduodenal ligament and Morison pouch was high even when the above-mentioned operative procedures were not performed. These findings may help inform clinical decisions regarding the indications and sites for adhesion barrier use during hepatectomies.

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. 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. 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. 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.

Background This study aimed to evaluate the prognostic impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma (HCC) in patients with alcohol-related liver disease (ALD). Patients and methods In total, 92 patients with ALD-HCC who underwent initial and curative hepatic resection were identified, including 56 and 36 patients with and without alcohol abstinence, respectively. Results The 3-, 5-, and 7-year recurrence-free survival (RFS) were 46%, 43%, and 37% in the abstinence group, and 61%, 36%, and 36% in the non-abstinence group, respectively (p = 0.71). The 3-, 5-, and 7-year overall survival (OS) were 91%, 76%, and 66% in the abstinence group, and 87%, 57%, and 44% in the non-abstinence group, respectively (p = 0.023). Multivariate analysis revealed that non-abstinence was an independent prognostic factor for OS (P = 0.026). The incidence rate of liver-related death including HCC-specific death, liver failure, and renal failure in cirrhosis (hepatorenal syndrome) between the non-abstinence and abstinence groups were 41.7% vs. 19.6% (p = 0.032). Worsening of the Child–Pugh grade at intrahepatic recurrence was more frequently observed in the non-abstinence (33.3%) than that in the abstinence group (6.5%) (p = 0.039). Conclusions Alcohol abstinence might improve the long-term survival of patients with ALD-HCC undergoing hepatic resection., Highlights • Non-abstinence after surgery was an independent prognostic factor for overall survival with a 2.2-fold increased risk. • Worsening of Child–Pugh grade at intrahepatic recurrence was less frequently observed in the abstinent patients. • Hepatic resection tended to be more frequently performed for the treatment of HCC recurrence in the abstinent patients. • The incidence rate of liver-related death was significantly lower in the abstinent patients.

Introduction This study aimed to investigate the predictive factors and classifications for difficulty of laparoscopic repeated liver resection (LRLR) in patients with recurrent hepatocellular carcinoma. Methods Sixty patients who underwent LRLR were included. Potential predictive factors for difficult LRLR included the approach of the previous liver resection (laparoscopic or open), the number of previous liver resections, a history of cholecystectomy in previous liver resection, the operative procedure of previous liver resection, whether the tumor was near the resected site of the previous liver resection, non-surgical treatments before the present surgery, and the difficulty scoring system for laparoscopic liver resection. The relationship between these factors and perioperative outcomes were evaluated to investigate the predictive factor for difficult LRLR. Results Univariate and multivariate analyses demonstrated that an open approach during previous liver resection, two or more previous liver resections, a history of previous liver resection with not less than sectionectomy, tumor near the resected site of the previous liver resection, and intermediate or high difficulty in the difficulty scoring system were independent risk factors for prolonged operative time and/or severe adhesion of LRLR. Three difficulty classifications were then suggested based on the number of these five predictive factors. The difficulty classification reflected operative time, intraoperative blood loss, and incidence of postoperative complication. Conclusion The difficulty of LRLR may be predicted by three difficulty classifications using five preoperative predictive factors.

Introduction We investigated the indications for laparoscopic liver resection (LLR) of mass-forming intrahepatic cholangiocarcinoma (MF-ICC), including the need for lymph node dissection for improved postoperative prognosis. Methods This study involved 36 patients who underwent surgery for solitary peripheral MF-ICC. Fifteen patients underwent LLR, and 21 underwent open liver resection (OLR). Surgical outcomes and prognostic factors were investigated to determine the indications for LLR. Results No significant differences were observed in perioperative outcomes between patients who underwent LLR and OLR. A significantly worse disease-free survival (DFS) rate was observed in patients who preoperatively had a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels. A significantly worse overall survival (OS) rate was observed in patients with a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 levels. Therefore, a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels were determined to be preoperative prognostic factors. DFS and OS rates were significantly better in patients without these factors. Moreover, in six patients without these factors who underwent LLR, neither lymph node metastasis nor postoperative recurrence was observed. Conclusion A tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels are preoperative prognostic factors for peripheral MF-ICC. LLR is indicated for patients without these factors.

A 82-year-old female had received radiofrequency ablation for hepatocellular carcinoma(HCC)in segment 2 30 months before surgery. One month before surgery, enhanced CT showed enhanced lesion about 20 mm in diameter in the abdominal wall along the needle-tract. There was no other recurrent lesion including liver. We diagnosed the lesion as needle-tract implantation and she underwent surgical resection of the abdominal rectus muscle and sheath including needle-tract. The pathological findings revealed well differentiated HCC. After the surgery, she underwent transcatheter arterial embolization for the recurrent HCC in segment 3 and segment 4. Twenty one months after the surgery, she has been alive without recurrence. Our case demonstrated that surgical resection of the needle-tract implantation of the HCC is one of the useful therapeutic options for the selected patients.

A 66-year-old female with upper abdominal pain was diagnosed the pancreatic tail cancer infiltrating into the stomach and transverse colon by computed tomography(CT). Umbilical metastasis(so called Sister Mary Joseph's nodule)and peritoneal metastases in pouch of Douglas were detected by FDG-PET. The patient was diagnosed as unresectable pancreatic cancer with distant metastases. Thus, she received FOLFIRINOX therapy. After 9 courses of FOLFIRINOX therapy and 15 courses of FOLFIRI therapy, the pancreatic tumor shrunk on CT. In addition, umbilical metastasis and peritoneal metastases disappeared on FDG-PET. Therefore, conversion surgery was scheduled. Fourteen months after the initial treatment, we performed distal pancreatectomy with left adrenalectomy partial gastrectomy, transverse colectomy, and umbilical resection. The patient was discharged 15 days after the operation without serious complications. Histopathological findings revealed the presence of adenocarcinoma infiltrating into the preperitoneal adipose tissue in the umbilicus. Histological therapeutic effect was Grade Ⅰb according to the 7th Edition of the General Rules for the Study of Pancreatic Cancer. Seven months after the operation, local recurrence was showed. The patient is still alive 2 years and 5 months since the initial treatment.

Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19-9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma.

A 76-year-old man was referred to our hospital for advanced hepatocellular carcinoma(HCC)with chronic hepatitis type B. Although he underwent right anterior sectionectomy and S3 segmentectomy, multiple recurrences were found in the hepatic remnant after 2 months. Transcatheter arterial chemoembolization(TACE)and transcatheter arterial infusion (TAI)were performed separately. One and a half month after the last TAI, AFP and PIVKA-Ⅱ levels markedly elevated, and multiple early enhancing nodules with portal vein tumor thrombosis were detected on CT. A half dose of sorafenib(400mg/ day)was administered to the patient who was refractory to TACE. Sorafenib was discontinued after 4 weeks because the patient developed general fatigue and anorexia(Grade 3). Furthermore, these adverse events became worse, and ascites appeared. He was hospitalized in the palliative care unit for best supportive care for 3 weeks and also received outpatient treatment for more than 14 months. Fifteen months after discontinuing sorafenib administration, his condition improved dramatically, and CT revealed that the multiple HCC had reduced in size. Moreover, the portal vein tumor thrombosis disappeared. As his performance status and liver function were well preserved, he underwent partial hepatectomy for residual HCC. The patient remains alive without recurrence at 18 months, despite no administration of sorafenib.This case demonstrates that sorafenib administration combined with surgical treatment could possibly cure advanced HCC refractory to TACE.

A 67-year-old woman was diagnosed with borderline resectable pancreatic cancer and obstructive jaundice. A covered self-expandable metallic stent(SEMS)was placed endoscopically. Neoadjuvant chemotherapy with gemcitabine plus nabpaclitaxel was provided. Forty-seven days after the SEMS placement, she presented with hematemesis. Computed tomography revealed migration of SEMS into the small bowel. No pseudoaneurysms were detected. Upper digestive endoscopy demonstrated hemobilia without obvious causes of bleeding in the stomach or duodenum. As hemorrhage recurrence was confirmed in the bile duct, we performed pancreaticoduodenectomy. Thus, bile duct hemorrhage can occur in patients with pancreatic cancer after SEMS placement.

The patient was an 81-year-old woman. She had undergone extended cholecystectomy with lymph node dissection for primary gallbladder cancer. The pathological diagnosis was moderately differentiated tubular adenocarcinoma(pT2, N0, M0, pStage Ⅱ). Eleven months after the initial surgery, dynamic CT revealed a solitary low-enhanced tumor in S5 ofthe liver. As the tumor was detected with abnormal FDG uptake by PET-CT, we diagnosed the patient with a metastatic liver tumor from gallbladder cancer. Although chemotherapy was considered, conservative treatment was selected as the patient did not want to undergo chemotherapy. Therefore, laparoscopic partial liver resection was performed 15 months after the initial surgery with the consideration that no other distant metastasis was found, and tumor markers were within normal ranges. The postoperative course was uneventful, and the patient was discharged 13 days after liver resection without any morbidities. The resected tumor was pathologically diagnosed as a metastatic liver tumor from gallbladder cancer. She has achieved 18 months recurrence free survival after the liver resection without adjuvant chemotherapy. Although liver resection for a metastatic liver tumor from gallbladder cancer is not a standardized treatment, it may be a therapeutic option in cases of limited metastasis.

Background This study aimed to evaluate the prognostic impact of the 5-5-500 rule in patients after hepatic resection for the intermediate stage of hepatocellular carcinoma (HCC; The Barcelona Clinic Liver Cancer classification [BCLC] B). Methods 177 patients had hepatic resection for BCLC-B HCC. The 5-5-500 rule was defined by tumor size ≤5 cm in diameter, tumor number ≤5, and α-fetoprotein ≤500 ng/mL. Results The 3-, 5-, and 7-year recurrence-free survival rates were 22%, 14%, and 11% in patients within the 5-5-500 rule, and 16%, 10%, and 10% in patients beyond the 5-5-500 rule, respectively (P = .015). The 3-, 5-, and 7-year overall survival rates were 72%, 47%, and 34% in patients within the 5-5-500 rule, and 52%, 31%, and 25% in patients beyond the 5-5-500 rule, respectively (P = .035). Being beyond the 5-5-500 rule and liver cirrhosis were independent prognostic factors for recurrence-free survival. For overall survival, being beyond the 5-5-500 rule, age ≥65 years, Child-Pugh class B, and anti-hepatitis C antibody positive were identified as independent prognostic factors. Conclusions The 5-5-500 rule could predict prognosis in BCLC-B patients with hepatic resection. Hepatic resection might provide survival benefit for selected patients with BCLC-B HCC within the 5-5-500 rule.

A 74-year-old woman presented with epigastric pain. Imaging revealed a tumor measuring 80 mm, with internal necrosis, originating from the gallbladder and invading the liver. We performed extended anterior segmentectomy of the liver and lymph node resection following a preoperative diagnosis of gallbladder cancer. Histologically, the tumor was diagnosed as an undifferentiated carcinoma of the gallbladder. Although curative resection was performed, the patient developed recurrence with liver metastasis and peritoneal dissemination after 6 postoperative weeks and died after 10 postoperative weeks.

In June 2018, a 75-year-old woman was admitted for right upper quadrant pain. She had a history of radical mastectomy for left breast cancer in April 2009. The axillary lymph node, bone, gastric, and pleural metastases had been treated with hormonal therapy for 2 years from April 2016. Based on the examination findings, we diagnosed her with acute calculous cholecystitis and performed emergency percutaneous transhepatic gallbladder drainage(PTGBD). Eleven days after PTGBD, we performed laparoscopic cholecystectomy. Pathological examination revealed a metastatic tumor from breast cancer in her gallbladder. Although her postoperative course was uneventful, the patient died of progression of the other organ metastasis 7 months after cholecystectomy. Gallbladder metastasis should be considered in patients with advanced breast cancer who present symptoms of cholecystitis.

Background: Although studies have reported on long-term (10-year) survival after hepatic resection for hepatocellular carcinoma (HCC), they did not focus on patients with hepatitis C virus (HCV)-related HCC, and the contribution of antiviral therapy to long-term survival (especially ≥15 years) has not been adequately examined. We investigated the long-term outcome after hepatic resection for HCV-related HCC, including the effects of interferon (IFN) therapy, and the changes in prognostic factors according to postoperative duration. Methods: The data of 207 patients who underwent hepatic resection for HCV-related HCC between January 1992 and December 2001 were retrospectively reviewed. We investigated the disease-free and overall survival rates after surgery and analyzed the prognostic factors at 5, 10, and 15 years postoperatively. Results: The proportion of patients who survived at 5, 10, and 15 years after hepatic resection was 52% (n = 107), 18% (n = 38), and 9% (n = 19). The overall survival rate was significantly higher in patients who achieved sustained virological response (SVR) with IFN therapy than in those without SVR. Tumor-related factors such as multiple tumor, microscopic vascular invasion, and a high indocyanine green retention rate at 15 min (ICGR15) were unfavorable prognostic factors for 5-year survival. Conversely, a low ICGR15 and SVR were favorable prognostic factors at 10 years, and SVR alone was a favorable prognostic factor at 15 years postoperatively; no tumor-related factors were prognostic factors at 10 and 15 years postoperatively. Conclusion: The prognostic factors varied according to the duration after hepatic resection for HCV-related HCC. Tumor-related factors were unfavorable prognostic factors in the early postoperative period, whereas SVR and good liver function were favorable prognostic factors at 10 and 15 years postoperatively. Achievement of SVR with IFN therapy is essential for long-term (≥15 years) survival after hepatic resection for HCV-related HCC.

A cluster of cholangiocarcinoma among printing company workers who were exposed to 1,2‐dichloropropane and/or dichloromethane was classified by the Ministry of Health, Labour and Welfare of Japan on 1 October 2013 as “occupational cholangiocarcinoma”. At the time of the diagnosis of cholangiocarcinoma, levels of γ‐glutamyl transferase, and aspartate and alanine aminotransferases were elevated, and had been elevated in some patients several years prior to the diagnosis. Regional dilatation of intrahepatic bile ducts without tumor‐induced obstruction was characteristic in diagnostic imaging. Pathological examination found chronic bile duct injury with DNA damage, precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct in various sites of the large bile ducts, and invasive cholangiocarcinoma such as mass‐forming type and intraductal growth‐type intrahepatic cholangiocarcinoma and mainly papillary‐type extrahepatic cholangiocarcinoma. Whole‐exome analysis of the cancerous tissues showed hypermutation, substantial strand bias, and unique trinucleotide mutational changes. Patients seemed to suffer high incidence of postoperative complications including intra‐abdominal, which might be related to chronic bile duct injury. Postoperative recurrence from multicentric origins occurred in some patients, as DNA‐injured bile ducts have high carcinogenic potential. Aggressive treatment, including second resections for such multicentric recurrences, appeared to be effective. In 2014, the International Agency for Research on Cancer classified 1,2‐dichloropropane as Group 1 (carcinogenic to humans) and dichloromethane as Group 2A (probably carcinogenic to humans) carcinogens.

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma.

Background Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. Methods Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. Results Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. Conclusions The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective.

Summary These occupational cholangiocarcinoma cases shared a high mutation burden, strand bias and unique trinucleotide mutational signatures, suggesting that the patients might have been exposed to a common strong mutagen. The underlying mechanisms of mutagenesis should be further investigated., Cholangiocarcinoma is a relatively rare cancer, but its incidence is increasing worldwide. Although several risk factors have been suggested, the etiology and pathogenesis of the majority of cholangiocarcinomas remain unclear. Recently, a high incidence of early-onset cholangiocarcinoma was reported among the workers of a printing company in Osaka, Japan. These workers underwent high exposure to organic solvents, mainly haloalkanes such as 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. We performed whole-exome analysis on four cases of cholangiocarcinoma among the printing workers. An average of 44.8 somatic mutations was detected per Mb in the genome of the printing workers’ cholangiocarcinoma tissues, approximately 30-fold higher than that found in control common cholangiocarcinoma tissues. Furthermore, C:G-to-T:A transitions with substantial strand bias as well as unique trinucleotide mutational changes of GpCpY to GpTpY and NpCpY to NpTpY or NpApY were predominant in all of the printing workers’ cholangiocarcinoma genomes. These results were consistent with the epidemiological observation that they had been exposed to high concentrations of chemical compounds. Whole-genome analysis of Salmonella typhimurium strain TA100 exposed to 1,2-DCP revealed a partial recapitulation of the mutational signature in the printing workers’ cholangiocarcinoma. Although our results provide mutational signatures unique to occupational cholangiocarcinoma, the underlying mechanisms of the disease should be further investigated by using appropriate model systems and by comparison with genomic data from other cancers.

BACKGROUND An outbreak of cholangiocarcinoma has been reported among workers of an offset color proof-printing department at a printing company in Japan. In this study, we compared the clinicopathological findings of this type of intrahepatic cholangiocarcinoma (occupational ICC) and non-occupational ICC. METHODS The clinical records of 51 patients with perihilar-type ICC who underwent liver resection, including five patients with occupational ICC were retrospectively reviewed. The clinicopathological features were compared. RESULTS In the occupational group, the patients were significantly younger (P

A 73-year-old man was diagnosed with essential thrombocythemia and treated with acetylsalicylic acid and hydroxyurea for 15 years. He was referred to our hospital for treatment of esophageal cancer detected by endoscopy. The cancer stage was T1N1M0, cStage IIB according to the classification of the Union for International Cancer Control, 7th edition. After administering two courses of preoperative chemotherapy (5-fluorouracil + cisplatin), the patient underwent video-assisted thoracoscopic radical esophagectomy. Hydroxyurea administration was discontinued during anticancer therapy and restarted to control the platelet count. Heparin was continuously infused during the perioperative period, and hydroxyurea was restarted through a jejunostomy tube on the postoperative day 2. No thrombosis or hemorrhage developed, and the patient was discharged from the hospital on the postoperative day 33. This is the first case report of video-assisted thoracoscopic radical esophagectomy for esophageal cancer in a patient with essential thrombocythemia.

Background This study aimed to investigate the association between non-alcoholic steatohepatitis (NASH) and intrahepatic cholangiocarcinoma (ICC). Methods This was a case control study of patients who underwent surgical resection either for ICC or for a metastatic liver tumor (the control group). We assessed their clinical characteristics, pathological findings, and the prevalence of known ICC risk factors. For patients without known risk factors, we compared other factors including the prevalence of NASH. Results In the patients without known risk factors, 15 of 34 patients in the ICC group and 13 of 69 patients in the control group were diagnosed with NASH. Univariate analysis showed significantly higher values in the ICC group for age (P = 0.0478), prevalence of obesity (P = 0.0365) and NASH (P = 0.0078), and serum levels of albumin (P = 0.0051), and gamma-glutamyl transpeptidase (γ-GTP) (P = 0.0006) compared with the control group. Multivariate analysis showed that age and serum levels of γ-GTP and NASH were independent risk factors for ICC. In patients with NASH, the proportion of patients with hepatic fibrosis was significantly higher in the ICC group than in the control group (P = 0.0014). Conclusion NASH is a possible risk factor for ICC development. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

The aim of the present study was to retrospectively identify prognostic factors for long-term cumulative survival following liver resection in patients with primarily unresectable colorectal cancer who had previously received conversion therapy. A multicentre study was designed to ascertain the appropriate indication for conversion therapy. The study included 34 patients who underwent conversion therapy at 5 university hospitals. Patients' background, operative factors, recurrence rate and survival rate were evaluated, and factors influencing therapy outcomes were identified. The median duration of preoperative chemotherapy was 3 months and the response rate was 39.8%. Upon resection, the median tumour size was 47 mm and the median number of tumours was 4. The recurrence-free and cumulative survival rates 5 years after liver resection were 13.7 and 39.3%, respectively. Postoperative complications developed in 12 patients. A response rate >40% was indicated with regards to the assessed prognostic factors for long-term cumulative survival following liver resection and an absence of postoperative complications was noted. It was revealed that conversion therapy should be considered prior to liver resection, particularly for patients with response rates exceeding 40%. Absence of postoperative complications is also an independent predictor of long-term cumulative survival after liver resection. In light of these findings, it was consisted that an optimal response rate >40% could be used as an indicator for surgical resection in conversion therapy. In addition, meticulous intra- and postoperative managements are important for decreasing postoperative complications and improving long-term cumulative survival.

Objective: The present study aimed to identify the clinical significance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in patients with occupational cholangiocarcinoma. Methods: This study included 10 men with occupational cholangiocarcinoma who were former or current workers at a printing company in Osaka, Japan. Of the 10 patients, 2 had 2 main tumors and 1 had 3 main tumors. Twelve FDG-PET imaging findings in the 10 patients could be analyzed. We evaluated the relationships between FDG-PET imaging parameters and clinicopathological findings of occupational cholangiocarcinoma. Results: Abnormal FDG uptake was observed in 8 of the 14 main tumors, with maximum standardized uptake values ranging from 2.9 to 11.0, and the sensitivity was 57.1%. Four patients had lymph node metastases, and abnormal marrow uptake was detected in all these patients. Although precancerous lesions, such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) without any invasion, were not detected, abnormal FDG uptake was demonstrated in 2 of 4 patients with IPNB having an associated invasive carcinoma.Conclusions: Although FDG-PET may be useful for assessing tumor progression factors, such as lymph node metastasis, it cannot accurately detect precancerous lesions, such as BilIN and IPNB without invasive carcinoma.

Background We aimed to identify the pathological characteristics of occupational cholangiocarcinoma. Methods We examined the location and distribution of the carcinomas: atypical epithelium including biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB); and chronic bile duct injuries in operative or autopsy liver specimens from 16 patients. We examined the detailed pathological findings and diagnostic imaging of three patients. Immunohistochemical analysis using primary antibodies against γH2AX and S100P was performed. Results BilIN and chronic bile duct injury were observed in 16 patients, and IPNB or invasive IPNB was observed in 11 patients. BilIN, IPNB, and/or chronic bile duct injury were observed in almost all the large bile ducts. Regional dilatation of the bile ducts without tumor-induced obstruction revealed such pathological changes. Highly positive results for the γH2AX and S100P markers were noted in invasive carcinoma, BilIN, and IPNB, whereas positive results for γH2AX and negative results for S100P were noted in non-neoplastic biliary epithelium. Conclusions The carcinogenic process of occupational cholangiocarcinoma comprised chronic bile duct injury and DNA damage in almost all the large bile ducts, along with induction of precancerous lesions and development of invasive carcinoma. Such pathological findings reflected radiological changes on diagnostic imaging.

Background Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor and is very rarely complicated by hemorrhage or rupture. Although thought to be extremely rare, there have been several reports of hemorrhage caused by ruptured FNH. Herein, we report the case of a patient with ruptured FNH, who subsequently developed hemorrhage during follow-up. Case presentation A 32-year-old man was admitted to our department for an asymptomatic hepatic tumor in segments 4 and 5 (S4/5), which measured 8 cm in diameter and observed to project from the liver. Imaging and pathologic examination of a biopsy specimen confirmed the diagnosis of FNH. Three years after the diagnosis, the patient was readmitted to our hospital because of sudden onset of upper abdominal pain. Dynamic abdominal computed tomography revealed ascites around the tumor with high-density areas that were considered to represent hematoma caused by ruptured FNH. Transcatheter arterial embolization (TAE) was performed to stop the hemorrhage. One month after TAE, S4/5 of the liver was resected; macroscopic findings revealed that a large part of the tumor was composed of necrotic tissue and hematoma. Pathological examination using hematoxylin–eosin staining and immunohistochemical examination indicated a final diagnosis of FNH rupture and hemorrhage. Conclusion Although a well-established diagnosis of FNH usually requires no treatment or surveillance, careful examination remains necessary when the FNH is large and projects from the liver because of the possibility of rupture and hemorrhage.

Objectives: A cholangiocarcinoma outbreak among workers of an offset color proof-printing department in a printing company was recently reported. It is important to understand the clinical course leading to occupational cholangiocarcinoma development for investigation of the carcinogenesis process and for surveillance and early detection. We evaluated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma. Methods: We investigated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma in 2 patients because the data were available. Results The clinical courses observed in the 2 participating patients showed persistent elevation of serum γ-glutamyl transpeptidase levels with or without elevated serum levels of alanine aminotransferase and/or aspartate aminotransferase before cholangiocarcinoma detection. Dilatation of the bile ducts without tumor-induced stenosis was observed several years before cholangiocarcinoma detection and progressed gradually in both patients. The serum concentration of carbohydrate 19-9 also increased prior to cholangiocarcinoma detection in both patients. Eventually, observation of stenosis of the bile duct and a space-occupying lesion strongly suggested cholangiocarcinoma. Pathological examination of the resected specimens showed chronic bile duct injury and neoplastic lesions, such as “biliary intraepithelial neoplasia” and “intraductal papillary neoplasm of the bile duct” in various sites of the bile ducts, particularly in the dilated bile ducts. Conclusions: The changes in laboratory test results and diagnostic imaging might be related to the development of cholangiocarcinoma. It is important to monitor diagnostic imaging presentation and laboratory test results in workers with extended exposure to organic solvents.(J Occup Health 2014; 56: 317-322)

Although several studies have reported the outcomes of surgery for the treatment of liver metastases of gastric cancer (GLM), indications for liver resection for gastric metastases remain controversial. This study was designed to identify prognostic determinants that identify operable hepatic metastases from gastric cancer and to evaluate the actual targets of surgical therapy. Retrospective analysis was performed on outcomes for 24 consecutive patients at five institutions who underwent gastrectomy for gastric cancer followed by curative hepatectomy for GLM between 2000 and June 2012. Overall 5-year survival and median survival were 40.1 % and 22.3 months, respectively. Uni- and multivariate analyses showed that liver metastatic tumour size less than 5 cm was the most important predictor of overall survival (OS, p = 0.03). Four patients survived >5 years. Repeat hepatectomy was performed in three patients. Two of these patients have remained disease-free since the repeat hepatectomy. GLM patients with metastatic tumour diameter less than 5 cm maximum are the best candidates for hepatectomy. Hepatic resection should be considered as an option for gastric cancer patients with liver metastases.

Background An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. Methods This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. Results The cholangiocarcinoma was diagnosed at 25–45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. Conclusions The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents.

A 63-year-old man was admitted to our hospital owing to weight loss and vertigo. Endoscopic examination revealed advanced gastric cancer type 2. Abdominal CT showed a 62mm liver tumor in segment 4 and a 26mm tumor in segment 8. Distal gastrectomy and D2 lymph node dissection were performed. After surgery, he was administered chemotherapy with S- 1. After 2 courses of treatment, the tumors' in segments 4 and 8 were reduced to 52mm and 16mm, respectively. No other metastases were detected. Left lobectomy and partial resection of segment 8 were performed. The pathological therapeutic effects were rated as Grade 1b for the tumor in segment 4 and Grade 3 for the tumor in segment 8. After hepatectomy, he was administered adjuvant chemotherapy with S-1 for 1 year. No recurrence has been detected for 4 years and 6months after hepatectomy.

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma.