Significance of Prediction Models for Post-Hepatectomy Liver Failure Based on Type IV Collagen 7s Domain in Patients with Hepatocellular Carcinoma.

Background: Previous studies have attempted to establish predictive models for post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) undergoing liver resection. However, a versatile and useful predictive model for PHLF remains to be developed. Therefore, we aimed to develop predictive models for PHLF based on type IV collagen 7s domain (7s collagen) in patients with HCC. Methods: We retrospectively collected data from 972 patients with HCC who had undergone initial curative liver resection between February 2000 and December 2020 at our hospital. Multivariate logistic regression analysis using a restricted cubic spline was performed to evaluate the effect of 7s collagen on the incidence of PHLF. A nomogram was developed based on 7s collagen. Results: PHLF grades B or C were identified in 104 patients (11%): 98 (10%) and 6 (1%) PHLF grades B and C, respectively. Multivariate logistic regression analysis revealed that the preoperative serum level of 7s collagen was significantly associated with a proportional increase in the risk of PHLF, which was confirmed in both laparoscopic and open liver resections. A nomogram was developed based on 7s collagen, with a concordance index of 0.768. The inclusion of 7s collagen values in the predictive model increased the predictive accuracy. Conclusion: The findings highlight the efficacy of the serum level of 7s collagen as a predictive factor for PHLF. Our novel nomogram using 7s collagen may be useful for predicting the risk of PHLF.

Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear. PATIENTS AND METHODS: This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies. RESULTS: Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group. CONCLUSIONS: Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs.

Impact of frailty on long-term outcomes after liver resection for hepatocellular carcinoma in elderly patients: A prospective study.

BACKGROUND: sFrailty affects short-term outcomes after liver resection in elderly patients. However, frailty's effects on long-term outcomes after liver resection in elderly patients with hepatocellular carcinoma (HCC) are unknown. METHODS: This prospective, single-center study included 81 independently living patients aged ≥65 years scheduled to undergo liver resection for initial HCC. Frailty was evaluated according to the Kihon Checklist, a phenotypic frailty index." We investigated and compared postoperative long-term outcomes after liver resection between patients with and without frailty. RESULTS: Of the 81 patients, 25 (30.9%) were frail. The proportion of patients with cirrhosis, high serum alpha-fetoprotein level (≥200 ng/mL), and poorly differentiated HCC was higher in the frail group than in the nonfrail group (n = 56). Among the patients with postoperative recurrence, the incidence of extrahepatic recurrence was higher in the frail group than in the nonfrail group (30.8% vs. 3.6%, P = 0.028). Moreover, the proportion of patients who underwent repeat liver resection and ablation for recurrence who met the Milan criteria tended to be lower in the frail group than in the nonfrail group. Although there was no difference in disease-free survival between the two groups, the overall survival rate in the frail group was significantly worse than that in the nonfrail group (5-year overall survival: 42.7% vs. 77.2%, P = 0.005). Results of the multivariate analysis indicated that frailty and blood loss were independent prognostic factors for postoperative survival. CONCLUSION: Frailty is associated with unfavorable long-term outcomes after liver resection in elderly patients with HCC.

Application of Indocyanine Green Fluorescence Imaging for Tumor Localization during Robot-Assisted Hepatectomy.

The efficacy of indocyanine green (ICG) fluorescence imaging for visualizing hepatic tumors in robot-assisted hepatectomy (RAH) should be validated. This study included 30 consecutive patients with 33 collective tumors who underwent RAH. ICG was administered at a dose of 0.5 mg/kg before surgery. ICG fluorescence imaging was performed intraoperatively. In total, 28 patients with a combined total of 31 tumors underwent ICG fluorescence imaging. Further, 26 (84%) tumors were identified on hepatic surfaces prior to hepatic transection. The fluorescence signals of eight tumors were detected on hepatic raw surfaces during parenchymal dissection, thereby enabling surgeons to adjust the transection planes to ensure appropriate surgical margins. One patient with intrahepatic cholangiocarcinoma tested positive for cancer cells at the dissected stump of the bile duct. However, in all patients in whom ICG fluorescence imaging was used, negative surgical margins were achieved at the site of the dissected hepatic parenchyma. On the other hand, one of two patients with ICG contraindications had a positive surgical margin surrounding the dissected hepatic parenchyma. The median operative time and volume of blood loss were 259 (range: 124-594) min and 150 (range: 1-1150) mL, respectively. ICG fluorescence imaging facilitates the easy identification of hepatic tumors, even in RAH. Hence, it can be useful for confirming appropriate surgical margins.

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

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

Deep Learning Model Based on Contrast-Enhanced Computed Tomography Imaging to Predict Postoperative Early Recurrence after the Curative Resection of a Solitary Hepatocellular Carcinoma.

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.

Development of intraductal papillary neoplasm of the bile duct in patients with occupational cholangiocarcinoma.

This study aimed to investigate the clinicopathological findings of intraductal papillary neoplasm of the bile duct (IPNB) in patients with occupational cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane to elucidate the development of IPNB to cholangiocarcinoma. The clinicopathological findings of 17 IPNB lesions according to the size (1.5-20 mm in diameter) and their comparison between type 1 (n = 9) and type 2 IPNBs (n = 8) were investigated. An IPNB of <5 mm in size was classified as micro IPNB (n = 7), while those ≥5 mm in size were classified as ordinary IPNB (n = 10). Both types 1 and 2 IPNBs were observed in micro IPNB, and their proportions were not different between micro and ordinary IPNBs. The clinicopathological characteristics of types 1 and 2 IPNBs were fundamentally similar to those previously reported. IPNB with invasive carcinoma was only found in ordinary IPNB although the proportions of low-grade and high-grade epithelium were not different between micro IPNB and ordinary IPNB. All IPNB exhibited γH2AX and S100P, indicating the occurrence of DNA injury and malignant transformation in micro and ordinary IPNBs. These results indicate that the carcinogens may induce micro IPNB with types 1 or 2 at the initiation and then develop ordinary IPNB with types 1 or 2, subsequently, progressing to IPNB with invasive carcinoma in patients with occupational cholangiocarcinoma.

Increasing incidence and severity of post-hepatectomy adhesion around the liver may be influenced by the hepatectomy-related operative procedures.

BACKGROUND: 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. METHODS: First hepatectomy-induced hard dense adhesions were evaluated from the surgical records and/or videos of 168 patients who underwent second hepatectomies. RESULTS: 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. CONCLUSION: 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.

Suppression of intrahepatic cholangiocarcinoma cell growth by SKI via upregulation of the CDK inhibitor p21.

Cholangiocarcinoma (CC) has a poor prognosis and different driver genes depending on the site of onset. Intrahepatic CC is the second-most common liver cancer after hepatocellular carcinoma, and novel therapeutic targets are urgently needed. The present study was conducted to identify novel therapeutic targets by exploring differentially regulated genes in human CC. MicroRNA (miRNA) and mRNA microarrays were performed using tissue and serum samples obtained from 24 surgically resected hepatobiliary tumor cases, including 10 CC cases. We conducted principal component analysis to identify differentially expressed miRNA, leading to the identification of miRNA-3648 as a differentially expressed miRNA. We used an in silico screening approach to identify its target mRNA, the tumor suppressor Sloan Kettering Institute (SKI). SKI protein expression was decreased in human CC cells overexpressing miRNA-3648, endogenous SKI protein expression was decreased in human CC tumor tissues, and endogenous SKI mRNA expression was suppressed in human CC cells characterized by rapid growth. SKI-overexpressing OZ cells (human intrahepatic CC cells) showed upregulation of cyclin-dependent kinase inhibitor p21 mRNA and protein expression and suppressed cell proliferation. Nuclear expression of CDT1 (chromatin licensing and DNA replication factor 1), which is required for the G1/S transition, was suppressed in SKI-overexpressing OZ cells. SKI knockdown resulted in the opposite effects. Transgenic p21-luciferase was activated in SKI-overexpressing OZ cells. These data indicate SKI involvement in p21 transcription and that SKI-p21 signaling causes cell cycle arrest in G1, suppressing intrahepatic CC cell growth. Therefore, SKI may be a potential therapeutic target for intrahepatic CC.

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

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

Indications of Laparoscopic Repeat Liver Resection for Recurrent Hepatocellular Carcinoma.

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.

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

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

The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size.

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. RESULTS: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07-1.59), 1.07 (95% CI 0.89-1.28), 1.31 (95% CI 1.06-1.62), and 1.81 (95% CI 1.03-3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69-2.14), 1.33 (95% CI 1.02-1.73), and 1.58 (95% CI 1.04-2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46-1.57), 1.34 (95% CI 1.01-1.8), and 1.57 (95% CI 1.03-2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83-4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98-5.54) in those with tumors measuring ≥5 cm. CONCLUSIONS: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

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

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

Impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma in patients with alcohol-related liver disease.

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.

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

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

Durable response after discontinuation of pembrolizumab therapy for intrahepatic cholangiocarcinoma: a case report.

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.

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma.

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.

Precancerous Lesions and Liver Atrophy as Risk Factors for Hepatolithiasis-Related Death after Liver Resection for Hepatolithiasis.

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.
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Prognostic value of expanded liver transplantation criteria-the 5-5-500 rule-in patients with hepatic resection for intermediate-stage hepatocellular carcinoma.

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.