Nara Medical University

With recent advances in chemotherapy for unresectable pancreatic ductal adenocarcinoma (PDAC) with liver metastasis (LM), attempts have been made to resect the primary tumor in patients showing favorable responses to anti-cancer treatment (so-called “conversion surgery”; CS). This study aimed to clarify the outcomes of CS for PDAC with LM in a nationwide multicenter study. This retrospective, multicenter study was conducted as a project study of the Japan Pancreas Society and included patients with PDAC with LM at initial diagnosis, diagnosed radiologically or intraoperatively (occult LM), who underwent CS after at least 4 months of chemotherapy between 2010 and 2022. Survival outcomes and prognostic factors were analyzed. 90 patients were enrolled from 31 Japanese institutions. Median duration of preoperative chemotherapy was 10.4 (range, 4.2–58.5) months, and gemcitabine plus nab-paclitaxel was the most common first-line regimen, followed by folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin. Liver metastasectomy was performed in 27 patients (30

Nivolumab plus ipilimumab (NIVO + IPI) is a standard first-line therapy for intermediate-risk and poor-risk metastatic renal cell carcinoma (mRCC), but the long-term prognostic impact of prior primary tumor resection in this setting remains unclear. We retrospectively reviewed patients with mRCC that received NIVO + IPI as first-line therapy at eight Japanese institutions between October 2015 and May 2022. Patients were stratified into groups according to timing of metastasis and prior primary tumor resection (cytoreductive nephrectomy; CN): a metachronous group, a synchronous/CN(+) group, and a synchronous/CN(−) group. Progression-free survival, overall survival, and tumor responses were compared among groups, with a median follow-up of 54 months. Among 135 eligible patients, 40 were classified into the metachronous group (30

To determine the prevalence of disability-free survival (DFS) five years after elective non-cardiac surgery in older adults, and to identify preoperative factors associated with DFS using conventional statistical analyses and machine learning methods. In this prospective cohort study conducted at a single tertiary hospital in Japan, 2878 patients aged ≥55 years who underwent elective non-cardiac surgery under general anesthesia between 2016 and 2018 were enrolled and followed for 5 years. DFS was defined as survival without significant functional disability, assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Multivariable logistic regression and machine learning models were used to identify preoperative predictive factors. At 5 years after surgery, 80.6

Wnt/β-catenin-activated rosette-forming carcinoma (WARFC) is a recently proposed cutaneous tumor entity characterized by rosette formation, CDX2 expression, RB1 loss, and Wnt/β-catenin pathway activation. Extracutaneous counterparts of WARFC have not been documented to date. We report a distinctive case of lung carcinoma closely resembling WARFC. An 80-year-old man with a smoking history presented with a rapidly enlarging lung nodule. The resected tumor consisted of a rosette-forming large cell carcinoma with a trabecular pattern and lacking neuroendocrine marker expression, combined with squamous cell carcinoma. The rosette-forming component showed aberrant nuclear β-catenin expression, diffuse CDX2 expression, and RB1 loss. Targeted sequencing identified a pathogenic APC splice-site mutation. This case likely represents the pulmonary counterpart of cutaneous WARFC. Pulmonary WARFC should be considered in the differential diagnosis of large cell lung carcinoma with neuroendocrine morphology.

An effective therapeutic strategy for suppressing liver fibrosis development should improve the overall prognosis of patients with chronic liver diseases. Despite efforts to develop anti-fibrotic agents, no drugs have yet been approved as anti-fibrotic treatments for humans. An alternative strategy may be to employ a clinically available agent that also exhibits anti-fibrotic activities, for which the safety of long-term administration has been proven. The aim of the current study was to elucidate the combined effect of clinically used interferon (IFN), ribavirin (Rib) and angiotensin-II receptor blocker (ARB) on liver fibrosis development in mice. A model of CCl4-induced hepatic fibrosis was used to assess the effect of IFN, Rib and ARB. IFN, Rib and ARB were administered after a two-week treatment with CCl4, and the hepatic indices of fibrosis were assessed at eight weeks. Single treatment with IFN, Rib or ARB at the clinically available comparable doses significantly attenuated the liver fibrogenesis associated with the suppression of the number of α-smooth muscle actin positive cells, and the hepatic transforming growth factor-β (TGF-β) mRNA. Hepatic neovascularization, which is also known to play a pivotal role in liver fibrogenesis, and vascular endothelial growth factor (VEGF), a potent angiogenic factor, were also markedly inhibited. Combination treatment with any two agents exerted a more potent inhibitory effect than any single treatment. Moreover, the triple cocktail treatment revealed further suppressive effects than any two agent combination. Furthermore, in vitro studies showed that similar combined effects were observed on the proliferation and TGF-β mRNA expression of activated hepatic stellate cells and endothelial cell tube formation. These results indicate that the cocktail combination treatment of clinically used IFN, Rib and ARB may provide a new strategy for anti-liver fibrosis therapy.