The significance of CDT1 expression in non-cancerous and cancerous liver in cases with hepatocellular carcinoma.

We previously reported that chromatin licensing and DNA replication factor 1 (CDT1) expression was associated with the extent of proliferation of atypical hepatocytes and the time to postoperative recurrence in cases of hepatocellular carcinoma (HCC). This study aimed to clarify the clinical significance or pathogenesis of CDT1 expression in both non-cancerous and cancerous liver in HCC cases, including previously published data. We investigated the association between the expression of CDT1 in non-cancerous or cancerous liver tissues and histologic findings or biochemical examination results in 62 cases. We also examined the dual localization between CDT1 and FbxW7, P57kip2, P53 and c-Myc by confocal laser scanning microscopy. CDT1 mRNA expression was significantly higher in cancerous liver than in non-cancerous liver (p<0.0001). Elevated CDT1 mRNA expression indicates a significantly degree of inflammatory cell infiltration within lobules, along with elevated serum transaminase levels, and hepatic spare decline. CDT1 mRNA was highly expressed in a group of poorly differentiated cancer cells. CDT1 co-localized with P57kip2, Fbwx7, P53 and c-Myc in the nucleus or cytoplasm of hepatocytes and cancer cells. We found that CDT1 mRNA expression could represent the degree of hepatic spare ability and the high carcinogenic state.

[Experience of Using Immune Checkpoint Inhibitors and Chemotherapy in the Upper Gastrointestinal Tract at Our Hospital].

We investigated the gastric and esophageal cancer cases treated with immune checkpoint inhibitors and chemotherapy at our hospital. Out of 17 gastric cancer cases, 9 were treated with nivolumab(Nivo)plus S-1/oxaliplatin(SOX), 5 with Nivo plus 5-fluorouracil/Leucovorin/oxaliplatin(FOLFOX), and 3 with Nivo plus capecitabine/oxaliplatin(CapeOX), yielding a response rate of 35.3%. We also treated 3 cases of esophageal cancer. Two of these were treated with Nivo plus cisplatin/5- fluorouracil(CF)and 1 case with pembrolizumab(Pembro)plus CF, with a response rate of 33.3%. The incidence of Grade 3 or higher adverse events was 29.4% in gastric cancer and 33.3% in esophageal cancer, and no serious immune-related adverse events were observed. Further case accumulation and long-term studies are required to evaluate efficacy and adverse events in clinical practice.

Impact of Sarcopenic Obesity on Severe Postoperative Complications in Patients with Gastric Cancer Undergoing Gastrectomy.

INTRODUCTION: Several studies have indicated that sarcopenia affects the short- and long-term outcomes of cancer patients, including those with gastric cancer. In recent years, sarcopenic obesity and its effects have been reported in cancer patients. This study aimed to evaluate the impact of sarcopenic obesity on postoperative complications in patients with gastric cancer undergoing gastrectomy. METHODS: This single-center, retrospective study included 155 patients who underwent curative gastrectomy for gastric cancer from January 2015 to July 2021. Sarcopenia was defined by the psoas muscle index (<6.36 cm2/m2 in men and <3.92 cm2/m2 in women), which measures the iliopsoas muscle area at the lumbar L3 level using computed tomography. Obesity was defined by body mass index (≥25). Patients with both sarcopenia and obesity were defined as the sarcopenic obesity group and others as the non-sarcopenic obesity group. Severe postoperative complications were defined as Clavien-Dindo classification grade IIIa or higher. RESULTS: Of the 155 patients, 26 (16.8%) had sarcopenic obesity. The incidence of severe postoperative complications was significantly higher in the sarcopenic obesity group (30.8% vs. 10.9%; p = 0.014). Multivariate analysis indicated that sarcopenic obesity was an independent risk factor for severe postoperative complications (odds ratio, 3.950; 95% confidence interval, 1.390-11.200; p = 0.010). CONCLUSION: Sarcopenic obesity is an independent risk factor for severe postoperative complications.

Effect of blood product transfusion on the prognosis of patients undergoing hepatectomy for hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: Hepatectomy, the most common treatment for hepatocellular carcinoma, is associated with greater intraoperative blood loss than is resection of other malignancies. The effect of blood product transfusion (red blood cell [RBC], platelet, fresh frozen plasma [FFP], 5 and 25% albumin) on prognosis remains unclear. This study examined effects of blood product transfusion on prognoses of patients who underwent hepatectomy for hepatocellular carcinoma. METHODS: We included 2015 patients with pathologically confirmed hepatocellular carcinoma who underwent hepatectomy at our institution during 1990-2019. Patients (n = 534) who underwent repeat hepatectomy, non-curative hepatectomy, those with synchronous cancer in other organs, those who died within 1 month of surgery, and those with missing data were excluded. Finally, 1481 patients (1142 males, 339 females; median age: 68 years) with curability A or B were included. RESULTS: Intraoperative blood loss (> 500 mL) was an independent predictor of RBC transfusion (odds ratio, 8.482; P < 0.001). All transfusion groups had poorer recurrence-free survival (RFS) and overall survival (OS) than non-transfusion groups. After propensity score matching, the 5 year RFS rate was 13.4 and 16.3% in the RBC and no-RBC groups, respectively (P = 0.020). The RBC group had a significantly lower 5 year OS rate than the no-RBC group (42.1 vs. 48.8%, respectively; P = 0.035) and the FFP group (57.0%) than the no-FFP group (63.9%) (p = 0.047). No significant between-subgroup differences were found for other blood transfusion types. CONCLUSIONS: RBC transfusion promotes hepatocellular carcinoma recurrence and RBC/FFP transfusions reduced long-term survival and RFS and OS in patients who underwent radical liver resection of HCC.

A nationwide certification system to increase the safety of highly advanced hepatobiliary-pancreatic surgery.

BACKGROUND: To ensure that highly advanced hepatobiliary-pancreatic surgery (HBPS) is performed safely, the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons established a safety committee to monitor surgical safety. METHODS: We investigated postoperative mortality rates based on summary reports of numbers and outcomes of highly advanced HBPS submitted annually by the board-certified training institutions from 2012 to 2019. We also analyzed summary reports on mortality cases submitted by institutions with high 90-day post-HBPS mortality rates and recommended site visits and surveys as necessary. RESULTS: Highly advanced HBPS was performed in 121 518 patients during the 8-year period. Thirty-day mortality rates from 2012 to 2019 were 0.92%, 0.8%, 0.61%, 0.63%, 0.70%, 0.59%, 0.48%, and 0.52%, respectively (P < .001). Ninety-day mortality rates were 2.1%, 1.82%, 1.62%, 1.28%, 1.46%, 1.22%, 1.19%, and 0.98%, respectively (P < .001). Summary reports were submitted by 20 hospitals between 2015 and 2019. Mortality rates before and after the start of report submission and audit were 5.72% and 2.79%, respectively (odds ratio 0.690, 95% confidence interval 0.487-0.977; P = .037). CONCLUSIONS: Development of a system for designation of board-certified expert surgeons and safety management improved the mortality rate associated with highly advanced HBPS.

The proliferation of atypical hepatocytes and CDT1 expression in noncancerous tissue are associated with the postoperative recurrence of hepatocellular carcinoma.

Recently, we reported that extent of proliferation of atypical hepatocytes (atypical hepatocytes) was most important histological risk factor for development of hepatocellular carcinoma (HCC) from chronic hepatitis C or liver cirrhosis. Here, we aimed to clarify whether the atypical hepatocytes in noncancerous sections is also involved in postoperative recurrence. Furthermore, we investigated significant genes involved in the atypical hepatocytes. Association between the extent of atypical hepatocytes in noncancerous tissue and postoperative recurrence was validated in 356 patients with HCC. Next, we identified putative signature genes involved in extent of atypical hepatocytes. First, atypical hepatocytes or hepatocytes other than the atypical hepatocyte in noncancerous sections of 4 HCC patients were selectively collected by laser capture microdissection (LCM). Second, the gene expression profiles of the selected hepatocyte populations were compared using Ion AmpliSeq Transcriptome Human Gene Expression Kit (Thermo Fisher SCIENTIFIC, Waltham, MA, USA) analysis. Finally, we validated the mRNA expression of the extracted genes in noncancerous frozen liver tissue from 62 patients with HCC by RT-qPCR to identify the signature genes involved in both the extent of atypical hepatocytes and postoperative recurrence. Furthermore, the extent of atypical hepatocytes and CDT1 expression in noncancerous sections from 8 patients with HCC were also validated by selectively collecting samples using LCM. The extent of atypical hepatocytes was associated with postoperative recurrence. Of the genes that showed significant differences in expression levels between two populations, the expression of the chromatin licensing and DNA replication factor 1 (CDT1) gene was most strongly associated with the extent of atypical hepatocytes and was also associated with postoperative recurrence. Furthermore, CDT1-positive cells that exhibited stronger expression resembled those morphologically considered to be atypical hepatocytes. CDT1 and Ki-67 were colocalized in the nuclei of both hepatocytes and cancer cells. The hepatocytes in noncancerous livers were not uniform in each hepatocyte population, suggesting that the accumulation of genetic abnormalities was variable. We found that the strong degree of atypical hepatocytes and high CDT1 mRNA expression represent a high carcinogenic state of the liver. Thus, we consider the evaluation of degree of these could support the personalized medicine.

Surgery versus Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Randomized Controlled Trial (SURF Trial).

Introduction: It remains unclear which surgery or radiofrequency ablation (RFA) is the more effective treatment for small hepatocellular carcinoma (HCC). We aimed to compare survival between patients undergoing surgery (surgery group) and patients undergoing RFA (RFA group). Methods: We conducted a randomized controlled trial involving 49 institutions in Japan. Patients with Child-Pugh scores ≤7, largest HCC diameter ≤3 cm, and ≤3 HCC nodules were considered eligible. The co-primary endpoints were recurrence-free survival (RFS) and overall survival (OS). The current study reports the final result of RFS, and the follow-up of OS is still ongoing. Results: During 2009-2015, 308 patients were registered. After excluding ineligible patients, the surgery and RFA groups included 150 and 151 patients, respectively. Baseline factors did not differ significantly between the groups. In both groups, 90% of patients had solitary HCC. The median largest HCC diameter was 1.8 cm (interquartile range [IQR], 1.5-2.2 cm) in the surgery group and 1.8 cm (IQR, 1.5-2.3 cm) in the RFA group. The median procedure duration (274 vs. 40 min, p < 0.01) and the median duration of hospital stay (17 days vs. 10 days, p < 0.01) were longer in the surgery group than in the RFA group. RFS did not differ significantly between the groups as the median RFS was 3.5 (95% confidence interval [CI], 2.6-5.1) years in the surgery group and 3.0 (95% CI, 2.4-5.6) years in the RFA group (hazard ratio, 0.92; 95% CI, 0.67-1.25; p = 0.58). Discussion/Conclusion: Our study did not show which surgery or RFA is the better treatment option for small HCC.

Laparoscopic-assisted modified Kugel herniorrhaphy for obturator hernia: a case report.

Obturator hernia (OH) is a relatively rare disease and there are various surgical procedures for treating it. We report the case of a patient with an OH who underwent laparoscopic-assisted modified Kugel herniorrhaphy. The patient was a 74-year-old woman admitted to our hospital with nausea and abdominal distension. A diagnosis of intestinal obstruction was made because abdominal computed tomography revealed incarcerated right OH. No apparent strangulation findings were observed, and reduction was performed under ultrasound guidance. Laparoscopic-assisted modified Kugel herniorrhaphy for OH was performed. There were no signs of the bowel necrosis. Pneumoperitoneum was temporarily discontinued, and the OH was repaired by the modified Kugel herniorrhaphy. Laparoscopy confirmed that the direct Kugel patch was placed at the appropriate position. Laparoscopic-assisted modified Kugel herniorrhaphy is considered to be safe and useful for patients with OH and is considered as one of the treatment options.

Validity of the Algorithm for Liver Resection of Hepatocellular Carcinoma in the Caudate Lobe.

BACKGROUND: We aimed to validate our algorithm for resecting Hepatocellular carcinoma (HCC) in the caudate lobe based on tumor location, tumor size, and indocyanine green clearance rate. METHODS: Patients who underwent curative resections for solitary HCC in the caudate lobe were included. The surgical outcomes of patients with HCC in the caudate lobe were compared with those of patients with HCC in other sites of the liver. RESULTS: After one-to-one matching, the caudate-lobe group (n = 150) had longer operation time, greater amount of bleeding, lower weight of resected specimens, and shorter distance between tumor and resection line than the other-sites group (n = 150), but the complication rates were not different between the groups (38.0% vs. 34.1%, P = 0.719). After a median follow-up period of 3.0 years (range, 0.3-16.2 years), the median overall survivals were 6.5 (95% confidence interval [CI], 5.3-7.9) and 7.5 years (95% CI, 6.3-9.7) in the caudate-lobe and other-site groups, respectively (P = 0.430). Median recurrence-free survivals in the caudate-lobe group (1.9 years; 95% CI, 1.4-2.7) had a tendency to be shorter than those in the other-sites group (2.3 years; 1.7-3.4) (P = 0.052). CONCLUSIONS: Patients' survival and complication rates in the caudate-lobe group were comparable to those in the other-sites group; therefore, our algorithm for resecting HCC in the caudate lobe is of clinical use.

Evaluation of Safety-Related Outcomes of One-Segment and More-Than-One-Segment High-Level Hepatectomy in Hepatocellular Carcinoma Based on the Japanese Board Certification System.

BACKGROUND: We evaluated the impact of the Japanese board certification system for expert surgeons (JBCSES) on complications and survival outcomes in hepatectomy for hepatocellular carcinoma. METHODS: The postoperative outcomes of 493 patients who underwent high-level liver surgery involving one-segment (OSeg) hepatectomy and more-than-one-segment (MOSeg) resection were compared before and after JBCSES establishment. After the establishment of the JBCSES, the patients' postoperative outcomes were compared using propensity score matching (PSM) to determine the influence of expert surgeons. RESULTS: The establishment of the JBCSES was associated with a decrease in the overall postoperative complication rates after high-level liver surgery from 50.2 to 38.1% (P = 0.008) and a decrease in Clavien-Dindo class ≥ IIIb complications from 10.2 to 5.0% (P = 0.035). The 90-day mortality rate decreased from 5.1 to 0.7% (P = 0.003), and the 5-year survival rate increased from 51.4 to 63.9% (P = 0.009). Using PSM, a comparison of OSeg hepatectomies that involved expert surgeons (n = 48) and those that did not (n = 48) showed significantly lower intraoperative blood loss in surgeries involving an expert surgeon (mean, 340 vs. 473 mL; P = 0.033). There were no significant differences in complication rates or long-term prognosis between these groups. A comparison of MOSeg hepatectomies that involved expert surgeons (n = 26) and those that did not (n = 26) showed no significant difference in surgical factors, complications, or overall survival between the two groups. CONCLUSIONS: After establishment of the JBCSES, postoperative complication rates and mortality rates decreased and survival rates increased following liver surgery. Expert surgeon participation significantly decreased intraoperative blood loss during OSeg hepatectomies.

Magnetic resonance elastography-based prediction of hepatocellular carcinoma recurrence after curative resection.

BACKGROUND: Liver stiffness measurement using magnetic resonance elastography can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection for hepatocellular carcinoma. The aim of this prospective study was to investigate whether preoperative liver stiffness measurement by magnetic resonance elastograhy can predict recurrence after curative resection for hepatocellular carcinoma. METHODS: Patients who underwent preoperative liver stiffness measurement and curative resection for hepatocellular carcinoma were enrolled in this study. Potential associations between liver stiffness measurement, along with other clinical and pathologic variables, and intrahepatic hepatocellular carcinoma recurrence were analyzed. RESULTS: In total, 156 patients were included in this study. During a median follow-up period of 25.1 months (range, 6.0-60.5 months), 72 (46.1%) patients with hepatocellular carcinoma had an intrahepatic recurrence. The median disease-free period after resection was 17.9 months (range, 1.0-60.5 months). In the multivariate analysis, liver stiffness measurement (hazard ratio, 1.27; 95% confidence interval, 1.11-1.43; P <.001) and vascular invasion (hazard ratio, 1.96; 95% confidence interval, 1.15-3.25; P = .013) were identified as independent predictors of recurrence. When the optimal cutoff point was set at 4.53 kPa using the minimal P value approach, the disease-free period after curative resection in 71 patients with a liver stiffness measurement value ≥4.53 kPa (11.3 months [range, 2.0-60.5 months]) was significantly shorter than that of 85 patients with a liver stiffness measurement value <4.53 kPa (22.5 months [range, 1.1-60.5 months]; P <.001). CONCLUSION: Liver stiffness measurement using magnetic resonance elastography is a useful preoperative predictor of intrahepatic recurrence after curative resection for hepatocellular carcinoma.

Impact of patient age on outcome after resection for hepatocellular carcinoma.

There is little information on the impact of aging on liver resection of hepatocellular carcinoma (HCC). The aim of study was to evaluate the prognostic impact of the patient's age on the long-term survival after resection of HCC. The postoperative outcomes of the 291 elderly (≥ 70 years) and 340 younger (< 70 years) patients underwent curative liver resection for HCC were analyzed using multivariate and propensity-score matching. Risk score were calculated from the results of Cox regression analysis. The overall survival rate was significantly lower in the elderly group than that in the younger group (p = 0.01). Factors related to overall survival were vascular invasion (absent vs. present, HR 2.25; 95% CI 1.52-3.33, p = 0.0001), albumin level (< 3.0 vs. ≥ 3.0 g/dl, HR 2.23; 95% CI 1.31-3.79, p = 0.003), and number of tumors (solitary vs. multiple, HR 1.68; 95% CI 1.24-2.27, p = 0.001). The results of risk-score analysis with a Cox proportional-hazards model indicated that the proportion of poor-risk patients was significantly higher in the elderly than in the younger group. Propensity-score matching analysis yielded 234 pairs of patients. There were no significant differences in baseline profiles or risk scores between the two groups (p = 0.43). There were also no significant differences in the overall survival between the two groups (p = 0.23). Advanced age does not have a significant impact on the outcomes of patients after resection of HCC.

Algorithm for Resecting Hepatocellular Carcinoma in the Caudate Lobe.

OBJECTIVE: To propose an algorithm for resecting hepatocellular carcinoma (HCC) in the caudate lobe. BACKGROUND: Owing to a deep location, resection of HCC originating in the caudate lobe is challenging, but a plausible guideline enabling safe, curable resection remains unknown. METHODS: We developed an algorithm based on sublocation or size of the tumor and liver function to guide the optimal procedure for resecting HCC in the caudate lobe, consisting of 3 portions (Spiegel, process, and caval). Partial resection was prioritized to remove Spiegel or process HCC, while total resection was aimed to remove caval HCC depending on liver function. RESULTS: According to the algorithm, we performed total (n = 43) or partial (n = 158) resections of the caudate lobe for HCC in 174 of 201 patients (compliance rate, 86.6%), with a median blood loss of 400 (10-4530) mL. Postoperative morbidity (Clavien grade ≥III b) and mortality rates were 3.0% and 0%, respectively. After a median follow-up of 2.6 years (range, 0.5-14.3), the 5-year overall and recurrence-free survival rates were 57.3% and 15.3%, respectively. Total and partial resection showed no significant difference in overall survival (71.2% vs 54.0% at 5 yr; P = 0.213), but a significant factor in survival was surgical margin (58.0% vs 45.6%, P = 0.034). The major determinant for survival was vascular invasion (hazard ratio 1.7, 95% CI 1.0-3.1, P = 0.026). CONCLUSIONS: Our algorithm-oriented strategy is appropriate for the resection of HCC originating in the caudate lobe because of the acceptable surgical safety and curability.

High C-reactive protein/albumin ratio associated with reduced survival due to advanced stage of intrahepatic cholangiocarcinoma.

C-reactive protein (CRP)- and albumin (Alb)-based scoring systems are available for predicting the prognosis of patients with diverse forms of gastrointestinal cancer, but their utility for patients with intrahepatic cholangiocarcinoma (ICC) is still unclear. This study aimed to elucidate whether a high CRP/Alb ratio is associated with the surgical outcome of ICC patients. Patients who underwent initial and curative resection for ICC were included in this study, and were divided into the High and Low CRP/Alb groups based on their preoperative CRP and Alb values. The surgical outcomes were compared between the two groups. The median CRP/Alb ratio amongst 88 patients was 0.033 (range, 0.019-3.636); 44 patients with CRP/Alb > 0.033 were allocated to the High CRP/Alb group and 44 patients were allocated to the Low CRP/Alb group. The operative data did not differ between the two groups, while the tumor status was more advanced in the High CRP/Alb group. The median overall survival was 2.4 years (95% CI, 1.4-3.3) and 8.9 years (3.8-NA) in the High and Low CRP/Alb groups, respectively (P < 0.001), and recurrence-free survival was 0.5 years (95% CI, 0.3-0.7) and 7.7 years (1.3-NA), respectively (P < 0.001). In a multivariate analysis, the independent factors for overall survival were High CRP/Alb (P = 0.017) and multiple nodules (P = 0.008). Taken together, the survival of ICC patients in the High CRP/Alb group was reduced compared to that of patients in the Low CRP/Alb group due to the advanced stage of the tumor as well as malnutrition.

Favorable outcomes of surgical resection for extrahepatic recurrent hepatocellular carcinoma.

AIM: Repeat resection for intrahepatic recurrent hepatocellular carcinoma (HCC) is effective for the long-term survival of patients; however, little is known about the surgical outcomes of extrahepatic nodules. The aim of this study is to investigate whether resection can contribute to the survival of patients with extrahepatic recurrent HCC. METHODS: Under the conditions that intrahepatic recurrent HCC was absent or controlled by locoregional therapies, patients who had resectable extrahepatic recurrent HCC in the lymph nodes, adrenal gland, peritoneum, lung, or brain were included in this study. The survival of patients who did (Surgical group) and did not (Non-surgical group, underwent other therapies) undergo resection for extrahepatic recurrent HCC was compared. RESULTS: Thirty-eight and 26 patients were included in the Surgical and Non-surgical groups, respectively. No patient had severe postoperative complications. After a median follow-up of 1.2 (range, 0.2-8.8) years, the median cumulative incidence of extrahepatic recurrent HCC was 1.2 years (95% confidence interval [CI], 0.4-3.5) in the Surgical group. The median overall survival was 5.3 (95% CI, 2.5-8.8) and 1.1 (0.8-2.3) years in the Surgical and Non-surgical groups, respectively (P < 0.001). The 5-year rates of survival were 60.5% and 9.1% in the Surgical and Non-surgical groups, respectively. Surgical resection, α-fetoprotein, disease-free interval, and metastasis at the adrenal gland were the independent factors for overall survival. CONCLUSIONS: Due to the favorable surgical outcomes, resection should be considered as one of the therapeutic choices for patients with extrahepatic recurrent HCC if intrahepatic recurrent HCC can be controlled by locoregional therapies.

Impact of marginal resection for hepatocellular carcinoma.

PURPOSE: The surgical margin for liver resection to treat hepatocellular carcinoma (HCC) is occasionally < 1 mm. This study determined the impact of a surgical margin < 1 mm [marginal resection (MR)] on the types of recurrence and the prognosis in solitary HCC. METHODS: The data of 454 patients undergoing curative liver resection for solitary HCC in our institution were analyzed. The patients were divided into the MR (n = 90) and non-MR (n = 364) groups. The clinicopathological data and outcomes after liver resection were compared. A case-matching analysis using a propensity scoring method was also performed. RESULTS: The recurrence-free survival was significantly and overall survival was marginally significantly lower in the MR group than in the non-MR group (p = 0.012-0.051, respectively). According to a multivariate analysis, MR was not a significant independent factor for recurrence-free survival (p = 0.056). After propensity score matching, there were no significant differences in the recurrence-free and overall survival between the two groups (p = 0.375-0.496, respectively). Furthermore, there were no significant differences in the intrahepatic recurrence patterns between the two groups before and after matching. CONCLUSION: MR for solitary HCC might be sufficient in patients with a limited liver functional reserve.

Liver Resection Versus Embolization for Recurrent Hepatocellular Carcinoma.

BACKGROUND: Despite curative resection, hepatocellular carcinoma (HCC) has a high probability of recurrence. We validated the potential role of liver resection (LR) for recurrent HCC. METHODS: Patients with intrahepatic recurrence with up to three lesions were included. We compared survival times of patients undergoing their first LR to those of patients undergoing repeated LR. Then, survival times of the patients who had undergone LR and transcatheter chemoembolization (TACE) for recurrent HCC after propensity score matching were compared. RESULTS: After a median follow-up period of 3.1 years (range, 0.2-16.3), median overall survival times were 6.5 years (95% CI 6.0-7.0), 5.7 years (5.2-6.2), and 5.1 years (4.9-7.3) for the first LR (n = 1234), second LR (n = 273), and third LR (n = 90) groups, respectively. Severe complications frequently occurred in the first LR group (p = 0.059). Operative times were significantly longer for the third LR group (p = 0.012). After the first recurrence, median survival times after one-to-one pair matching were 5.7 years (95% CI 4.5-6.5) and 3.1 years (2.1-3.8) for the second LR group (n = 146) and TACE group (n = 146), respectively (p < 0.001). The median survival time of the third LR group (n = 41) (6.2 years; 95% CI 3.7-NA) was also longer than that of TACE group (n = 41) (3.4 years; 1.8-4.5; p = 0.010) after the second recurrence. CONCLUSIONS: Repeated LR for recurrent HCC is the procedure of choice if there are three or fewer tumors.

Patients' prognosis of intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma after resection.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC-CC who underwent resection in order to elucidate whether the classification of ICC and cHCC-CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC-CC who underwent liver resection from 2001 to 2017. Clinic-pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence-free survival (RFS) in both groups (P < .001 for both). Of note, for patients with ICC, tumor cut-off size of 5 cm showed statistical significance in median RFS (>5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC-CC, tumor cut-off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC-CC was 0.9 years (95% confidence interval: 0.3-1.6), which was poorer than that of patients with ICC (1.3 years, 0.5-2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC-CC into different categories because of a significant difference in RFS between the two.

Prior hepatitis B virus infection as a co-factor of chronic hepatitis C patient survival after resection of hepatocellular carcinoma.

BACKGROUND: Prior hepatitis B virus infection (PBI) may increase the risk of developing hepatocellular carcinoma (HCC), but the impact of PBI on clinical outcomes following treatment for HCC remains unknown. The aim of this study was to clarify whether PBI affects clinical outcomes after liver resection for hepatitis C virus (HCV)-related HCC by retrospective cohort study. METHODS: PBI patients were defined as those negative for hepatitis B surface antigen and positive for anti-hepatitis B core antibody. Surgical outcomes of HCV-related HCC patients with PBI were compared to those without PBI. Survival of patients with non-B non-C HCC with and without PBI were also compared. RESULTS: In the HCV group, the median overall survival of 165 patients with PBI was 4.7 years (95% confidence interval [CI], 3.9-5.9), and was significantly shorter compared with 263 patients without PBI (6.6 years [5.3-9.8]; p = 0.015). Conversely, there was no significant difference in recurrence-free survival between the two groups (1.8 years [95% CI, 1.4-2.0] vs 2.0 years [1.7-2.3]; p = 0.205). On Cox proportional hazards regression model, independent factors for overall survival were PBI (hazard ratio 1.38 [95% CI, 1.02-1.87]; p = 0.033), multiple tumors (p = 0.007), tumor size (p = 0.002), and liver cirrhosis (p <  0.001). On the other hand, in the non-B non-C HCC group, both the median overall survival (6.5 years [95% CI, 4.8-7.1]) and recurrence-free survival (2.4 years, [95% CI, 1.5-3.3]) in 104 patients with PBI were not significantly different from those (7.5 years [5.5 - NA; p = 0.932]; and 2.2 years [1.7-2.7; p = 0.983]) in 213 patients without PBI. CONCLUSIONS: PBI and HCV in conjunction with each other affect the survival of patients that have undergone resection for HCC.

Liver resection for recurrent hepatocellular carcinoma after radiofrequency ablation therapy.

AIM: Although radiofrequency ablation (RFA) is an effective local treatment of hepatocellular carcinoma (HCC), local recurrence is relatively frequent. We aimed to elucidate the validity of salvage liver resection for recurrent HCC after RFA. METHODS: Patients who underwent liver resection for recurrent HCC after RFA (LR after RFA) and those who underwent second liver resection for recurrent HCC (second LR) were included. The short-term outcomes were compared between the two groups. The survival rates between the two groups were compared after propensity-score matching to adjust for the variables, including patient background, liver function, and tumor status. RESULTS: Major resection was frequently carried out in the LR after RFA group, but there was no significant difference both in operative data and complication rate between LR after RFA (n = 54) and second LR (n = 266) groups. After a median follow-up period of 1.8 years (range, 0.2-10.5), the median overall survival was 4.4 years (95% confidence interval [CI], 2.2 - not applicable) and 5.6 years (95% CI, 4.5-7.3; P = 0.023) in the LR after RFA group (n = 54) and second LR group (n = 54), respectively, and recurrence-free survival was 1.3 years (0.4-2.2) and 1.2 years (0.5-1.8, P = 0.469), respectively. The only independent factor for overall survival of the LR after RFA group was local recurrence (hazard ratio, 2.73; 1.06-9.00). CONCLUSIONS: Salvage liver resection of recurrent HCC after RFA could be recommended due to the safety of the procedure, especially in patients without local tumor progression after RFA.