Hippo-TAZ signaling is the master regulator of the onset of triple-negative basal-like breast cancers.

Breast cancer is the most frequent malignancy in women worldwide. Basal-like breast cancer (BLBC) is the most aggressive form of this disease, and patients have a poor prognosis. Here, we present data suggesting that the Hippo-transcriptional coactivator with PDZ-binding motif (TAZ) pathway is a key driver of BLBC onset and progression. Deletion of Mob1a/b in mouse mammary luminal epithelium induced rapid and highly reproducible mammary tumorigenesis that was dependent on TAZ but not yes-associated protein 1 (YAP1). In situ early-stage BLBC-like malignancies developed in mutant animals by 2 wk of age, and invasive BLBC appeared by 4 wk. In a human estrogen receptor+ luminal breast cancer cell line, TAZ hyperactivation skewed the features of these luminal cells to the basal phenotype, consistent with the aberrant TAZ activation frequently observed in human precancerous BLBC lesions. TP53 mutation is rare in human precancerous BLBC but frequent in invasive BLBC. Addition of Trp53 deficiency to our Mob1a/b-deficient mouse model enhanced tumor grade and accelerated cancer progression. Our work justifies targeting the Hippo-TAZ pathway as a therapy for human BLBC, and our mouse model represents a powerful tool for evaluating candidate agents.

Impact of bile leak on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection.

PURPOSE: The impact of postoperative bile leak on the prognosis of patients with hepatocellular carcinoma who underwent liver resection is controversial. This study aimed to investigate the prognostic impact of bile leak for patients with hepatocellular carcinoma who underwent liver resection. METHODS: Patients with hepatocellular carcinoma who underwent liver resection between 2009 and 2019 at Kobe University Hospital and Hyogo Cancer Center were included. After propensity score matching between the bile leak and no bile leak groups, differences in 5-year recurrence-free and overall survival rates were evaluated using the Kaplan-Meier method. RESULTS: A total of 781 patients, including 43 with postoperative bile leak, were analyzed. In the matched cohort, 40 patients were included in each group. The 5-year recurrence-free survival rates after liver resection were 35% and 32% for the bile leak and no bile leak groups, respectively (P = 0.857). The 5-year overall survival rates were 44% and 54% for the bile leak and no bile leak groups, respectively (P = 0.216). CONCLUSION: Overall, bile leak may not have a profound negative impact on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection.

Efficacy and safety of laparoscopic liver resection for hepatocellular carcinoma in segment 8: a propensity score-matched two-center study.

BACKGROUND: The safety and efficacy of laparoscopic liver resection (LLR) have been reported worldwide. However, those of LLR for tumors located in Couinaud's segment 8 are not sufficiently investigated. METHODS: We retrospectively analyzed 108 patients who underwent liver resection for hepatocellular carcinoma (HCC) in segment 8 at Kobe University Hospital and Hyogo Cancer Center between January 2010 and December 2021. The patients were categorized in LLR and open liver resection (OLR) groups, and 1:1 propensity score matching (PSM) was performed to compare surgical outcomes between the groups. RESULTS: Forty-seven and 61 patients underwent LLR and OLR, respectively. After PSM, each group contained 34 patients. There was no significant difference in operation time between the groups (331 min vs. 330 min, P = 0.844). Patients in the LLR group had significantly less blood loss (30 mL vs. 468 mL, P < 0.001) and shorter length of postoperative hospital stay (10 days vs. 12 days, P = 0.015) than those in the OLR group. There was no significant difference in the occurrence of postoperative complications between the groups (12% vs. 9%, P = 0.690). Further, the 1-year cumulative incidence of recurrence was not significantly different between the groups (16% vs. 19%, P = 0.734). CONCLUSIONS: The surgical outcomes and short-term prognosis of LLR were similar or better than those of OLR. LLR could be an effective and safe procedure, even for lesions located in segment 8, which is considered a difficult anatomical location for LLR.

[A Case of Carcinomatous Meningitis Due to Gastric Cancer].

A 43-year-old man was diagnosed with gastric cancer with diaphragm invasion and multiple lymph node metastases and underwent total gastrectomy. The histological diagnosis was por2>tub2, ypT4b(diaphragm), int, INF c, ly1, v1, ypN3, yp Stage ⅢC. Three months postoperatively, computed tomography showed recurrence in the peritoneum and multiple lymph nodes, and he received chemotherapy(RAM plus PTX). After initiating the third course of chemotherapy, he was hospitalized due to loss of appetite and fatigue. On the third day of hospitalization, he lost consciousness and had a temporary convulsion seizure. Thereafter, he complained of headache and nausea. Brain magnetic resonance imaging and cerebrospinal fluid examination lead to a diagnosis of carcinomatous meningitis due to gastric cancer. An Ommaya reservoir was placed, and intrathecal infusion with methotrexate(MTX)and cytarabine(Ara-C)was planned; however, intrathecal infusion could not be administered because of hepatic injury due to acute obstructive cholangitis. He died 6 months postoperatively. Carcinomatous meningitis has a rapidly progressive course with very poor prognosis. Early diagnosis is important, and the treatment should be initiated as soon as possible. Moreover, an effective standard treatment for carcinomatous meningitis needs to be established.

Assessment of serum and drain fluid bilirubin concentrations in liver transplantation patients.

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