Evaluation of two-stage hepatectomy using portal vein embolization for colorectal liver metastasis: a retrospective nationwide cohort survey in Japan.

INTRODUCTION: Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM) which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM. METHODS: We conducted a retrospective cohort study using the nationwide database that included clinical information of 12,519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher's exact test, chi-squared test and Mann-Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan-Meier method and log-rank test. RESULTS: Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rate at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95%CI 1.224-14.99, P= 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P= 0.004). CONCLUSION: In the Japanese cohort, TSH was confirmed to be a safety procedure with acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcome of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH.

Carbon-ion radiotherapy for hepatocellular carcinoma with major vascular invasion: a retrospective cohort study.

BACKGROUND: Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. METHODS: This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan-Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. RESULTS: In total, 76 patients with a median age of 71 years (range, 45-86 years) were evaluated. Among them, 68 had Child-Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5-180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7-79.4%), 32.7% (95% CI: 22.0-43.8%), and 8.9% (95% CI: 1.7-23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. CONCLUSIONS: C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.

Prognostic impact of proximal ductal margin status in perihilar cholangiocarcinoma according to the presence or absence of lymph node metastasis.

BACKGROUND: Although both proximal ductal margin status and lymph node metastasis status influence the survival of patients with perihilar cholangiocarcinoma, the effect of proximal ductal margin status on survival according to lymph node metastasis status is unclear. The aim of this study was, thus, to evaluate the prognostic impact of proximal ductal margin status in perihilar cholangiocarcinoma according to the presence or absence of lymph node metastasis. METHODS: Consecutive patients with perihilar cholangiocarcinoma who underwent major hepatectomy between June 2000 and August 2021 were retrospectively reviewed. Patients with Clavien-Dindo grade V complications were excluded from the analysis. Overall survival was assessed according to the combination of lymph node metastasis and proximal ductal margin status. RESULTS: Of the 230 eligible patients, 128 (56%) were lymph node metastasis negative, and 102 (44%) were lymph node metastasis positive. Overall survival was significantly better in lymph node metastasis negative than lymph node metastasis positive patients (P < .0001). Of the 128 lymph node metastasis-negative patients, 104 (81%) were proximal ductal margin negative, and 24 (19%) were proximal ductal margin positive. In lymph node metastasis-negative patients, overall survival was worse in the proximal ductal margin positive than the proximal ductal margin negative group (P = .01). Of the 102 lymph node metastasis-positive patients, 72 (71%) were proximal ductal margin negative and 30 (29%) were proximal ductal margin positive. In these patients, overall survival was similar between the 2 groups (P = .10). CONCLUSION: In patients with perihilar cholangiocarcinoma, the prognostic impact of proximal ductal margin positivity on survival might differ according to the presence or absence of lymph node metastasis.

High-risk HPV-related squamous cell carcinoma in the temporal bone: a rare but noteworthy subtype.

High-risk human papillomavirus (HPV) is a risk factor for the development of several head and neck squamous cell carcinomas (SCCs). However, there have been few reports of high-risk HPV infection in temporal bone squamous cell carcinomas (TBSCCs), and thus the prevalence and clinicopathologic significance of high-risk HPV in TBSCCs are still unclear. We retrospectively collected 131 TBSCCs and analyzed them for transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization; we also assessed the utility of p16-immunohistochemistry (IHC) and Rb-IHC to predict HPV infection. Eighteen (13.7%) of the 131 TBSCCs were positive for p16-IHC, and five of them were positive for high-risk HPV infection (the estimated high-risk HPV positivity rate was 3.8% [5/131]). Interestingly, all five HPV-positive patients were male and had TBSCC on the right side. In the p16-IHC+/HPV+ cases (n = 5), the Rb-IHC showed a partial loss pattern (n = 4) or complete loss pattern (n = 1). In contrast, all p16-IHC-negative cases (n = 113) showed an Rb-IHC preserved pattern. The positive predictive value (PPV) of p16-IHC positivity for high-risk HPV infection was low at 27.8%, while the combination of p16-IHC+/Rb-IHC partial loss pattern showed excellent reliability with a PPV of 100%. The prognostic significance of high-risk HPV infection remained unclear. High-risk HPV-related TBSCC is an extremely rare but noteworthy subtype.

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.

Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan.

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.

Validation study of the JSHBPS nomogram for patients with colorectal liver metastases who underwent hepatic resection in the recent era - a nationwide survey in Japan.

BACKGROUND: The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) nomogram was developed to predict disease-free survival in patients with colorectal liver metastases (CRLM) undergoing upfront hepatectomy. However, the utility of the nomogram in patients with resected CRLM remains unknown in the current situation in which treatment strategies are changing with advances in drugs. METHODS: Patients in the initial nomogram cohort (n = 727) and validation cohort (n = 2225) were divided into the upfront hepatectomy and preoperative chemotherapy groups. The nomogram was validated by measuring calibration and discrimination in the two cohorts. Calibration curves were plotted, and survival probabilities were compared. Finally, to quantify the discrimination power, we estimated the concordance index (C-index). RESULTS: In the upfront hepatectomy group, the C-index was 0.63, the suitable cutoff value of the Beppu score was 7, and adjuvant chemotherapy was significantly effective limited to high-risk patients (Beppu score ≥7). The C-index was 0.56 in the preoperative chemotherapy group. CONCLUSIONS: The JSHBPS nomogram remains beneficial for patients undergoing upfront hepatectomy in the recent era but is less effective for patients undergoing hepatectomy after chemotherapy. Patients with a Beppu score ≥7 showed high-risk recurrence, and adjuvant chemotherapy should be recommended for these patients.

Clinical Analysis of En Bloc Resection for Advanced Temporal Bone Squamous Cell Carcinoma.

Objective En bloc and margin-negative surgical resection seems to offer the best prognosis for patients with temporal bone squamous cell carcinoma (TB-SCC). In this study, we summarize the outcomes of surgical cases of advanced TB-SCC (T3-T4) that were managed in two institutions, with an accompanying description of the surgical procedure that was utilized: modified subtotal temporal bone resection (STBR), which involves the en bloc removal of the temporal bone including or transecting the otic capsule. Design This is a case series study with chart review. Setting The study was conducted at two academic tertiary care medical centers. Participants Chart information was collected for all patients who underwent surgical resection of advanced TB-SCC between July 1998 and February 2019. The resulting dataset contained 43 patients with advanced TB-SCC who underwent en bloc resection during the review period. Tumor staging followed the modified Pittsburgh classification. Disease-specific survival (DSS) rates were calculated according to the Kaplan-Meier method. Main Outcome Measure This study shows disease-specific 5-year DSS rate. Results The 5-year DSS rate of the cases who underwent en bloc resection was 79.7%. En bloc lateral temporal bone resection was employed in a total of 25 cases (DSS: 79.0%). En bloc modified STBR was utilized in 18 cases (DSS: 81.7%). Conclusion En bloc margin-negative resection is a reliable treatment strategy for advanced TB-SCC. Modified STBR can be a treatment option for TB-SCC without marked posterior extension.

Preoperative Diagnosis of Lymph Node Metastasis of Perihilar Cholangiocarcinoma Using Diffusion-Weighted Magnetic Resonance Imaging.

INTRODUCTION: Although the prognosis of patients with resected perihilar cholangiocarcinoma (PHC) with histological lymph node metastasis (LNM) is poor, preoperative prediction of LNM is difficult. This study aimed to evaluate the diagnostic performance of diffusion-weighted magnetic resonance imaging (DWI) for LNM of PHC. METHOD: Consecutive patients who underwent surgical resection of PHC between January 2012 and May 2020 were retrospectively reviewed. The lymph node (LN) area (mm2) and apparent diffusion coefficient (ADC) value ( × 10-3 mm2/s) of pericholedochal LNs were measured by DWI. The characteristics of the patients and the LNs were evaluated according to the histological presence or absence of regional LNM. Univariate and multivariate analyses were performed to identify the predictors of LNM of PHC. RESULTS: Of the 93 eligible patients, 49 (53%) were LNM positive and 44 (47%) were LNM negative. Although the characteristics of the patients were similar between the two groups, the mean ADC value was significantly lower in the LNM positive group than in the LNM negative group. On multivariate analysis, mean ADC value ≤1.80 × 10-3 mm2/s was independently associated with LNM of PHC (risk ratio: 12.5, 95% confidence interval: 3.05-51.4; p = 0.0004). The sensitivity, specificity and accuracy of mean ADC values ≤ 1.80 × 10-3 mm2/s for predicting LNM of PHC were 94%, 55% and 75%, respectively. CONCLUSIONS: DWI might be useful for the preoperative diagnosis of LNM of PHC.

Efficacy of side-to-end anastomosis to prevent anastomotic leakage after anterior resection for rectal cancer.

The present study aimed to investigate whether side-to-end anastomosis could provide an improved surgical outcome, such as lower anastomotic leakage rate, compared with end-to-end anastomosis, following anterior resection for rectal and rectosigmoid cancer. This retrospective study included 162 patients with rectal cancer who underwent elective anterior resection between January 2012 and October 2019 at a single institution. Patients with double cancers or colonic J-pouch were excluded. Anastomotic leakage was defined clinically and radiologically. Side-to-end anastomosis was introduced in the International University of Health and Welfare Mita Hospital in January 2017. Side-to-end anastomosis was performed in 63 patients, while end-to-end anastomosis was performed in 99 patients. Tumors tended to be located lower in the rectum in the side-to-end anastomosis group than in the end-to-end anastomosis group. No significant differences were observed in other patient characteristics. The incidence of anastomotic leakage was significantly lower in the side-to-end anastomosis group than in the end-to-end anastomosis group (3/63, 4.8% vs. 18/99, 18.2%, respectively, P=0.02). No significant differences were observed in the incidence rates of other complications. Univariate and multivariate analyses revealed that a smoking habit (P=0.04) and side-to-end anastomosis (P=0.02) were significantly associated with anastomotic leakage. In conclusion, side-to-end anastomosis using a double-stapling technique following anterior resection for rectal cancer may prevent anastomotic leakage.

Pancreatic serous cystadenocarcinoma diagnosed with liver metastasis at 7 years after the resection of the primary serous neoplastic lesion.

Pancreatic serous neoplasms are rare tumors that are usually benign. However, histopathological differentiation between benign (serous cystadenoma) and malignant (serous cystadenocarcinoma) lesions is difficult. We present the case of a patient with pancreatic serous cystadenocarcinoma that was diagnosed with liver metastasis 7 years after the resection of the primary serous neoplastic lesion. A woman in her 60 s was diagnosed with pancreatic serous cystadenoma based on imaging and histopathological examination findings. The tumor was resected, and the patient was followed up every 6 months to monitor tumor progression. At 7 years after the resection of the primary lesion, liver tumors showing marked flare-like contrast enhancements were detected on arterial phase computed tomography findings and on dynamic magnetic resonance imaging findings acquired 60 s after the administration of a contrast agent. Laparoscopic segmental hepatectomy of S4 and S6 was performed to resect these tumors. Histopathological examination revealed that these tumors were metastatic and developed from the primary lesion. Therefore, a diagnosis of serous cystadenocarcinoma was confirmed. The flare-like contrast enhancement around the metastatic liver lesions on computed tomography and dynamic magnetic resonance images may be an indicator of serous cystadenocarcinoma with liver metastasis that could assist in diagnosis.

Surgical implications of the confluence patterns of the left intrahepatic bile ducts in right hepatectomy for perihilar cholangiocarcinoma.

BACKGROUND: Although the most important goal in surgery for perihilar cholangiocarcinoma (PHC) is to achieve tumor-free proximal ductal margins, little is known about the implications of confluence patterns of the left intrahepatic bile ducts for the proximal ductal margin status in right hepatectomy (RH) for PHC. METHODS: Of 203 patients who underwent surgical resection for PHC with curative intent, confluence patterns of the left intrahepatic bile duct were evaluated in 94 consecutive patients who underwent RH, and they were classified into the following two types: normal type: the bile duct of segment 4 (B4) drained into the common trunk of the bile ducts of segment 2 (B2) and segment 3 (B3) at the right side of the umbilical portion of the left portal vein to form the left hepatic duct; and hepatic confluence type: B2 entered the common trunk of B3 and B4 at the hepatic confluence or B4 entered the common trunk of B2 and B3 at the hepatic confluence. The proximal ductal margin status following RH was compared between the two types of confluence patterns. RESULTS: Of 94 consecutive patients, 69 (73%) were the normal type, and 25 (27%) were the hepatic confluence type. There were no significant differences in patients' characteristics, surgical characteristics, surgical outcomes, and histopathological features between the two groups. However, in patients with Bismuth-Corlette type II and IIIa PHC, the achievement rates of negative proximal ductal margins at the first dividing line were significantly higher in the hepatic confluence type group than in the normal type group (16/16 [100%] vs 34/52 [65%], respectively; P = .007). CONCLUSIONS: Confluence patterns of the left intrahepatic bile ducts might affect proximal ductal margin status in RH for PHC.