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BACKGROUND: Neoadjuvant therapy has been increasingly adopted for resectable pancreatic ductal adenocarcinoma (PDAC) in Japan following the Prep-02/JSAP-05 trial. However, real-world evidence regarding effectiveness and underlying pathological mechanisms remains limited. This retrospective study evaluated neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) impacts on resectable PDAC patient oncological and pathological outcomes. METHODS: Consecutive resectable PDAC patients treated with NAC-GS (n = 60) or upfront surgery (UFS) (n = 101) between 2013 and 2023 were retrospectively analyzed (total diagnosed during the study period, n = 186). An intention-to-treat principle assessed overall survival (OS) and recurrence-free survival (RFS). Propensity score matching using six baseline variables (1:1) minimized selection bias. RESULTS: Fifty-four patients were included in each group. The NAC-GS group demonstrated significantly longer OS than the UFS group (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90; P = 0.023). Among resected cases, NAC-GS was associated with improved OS (HR, 0.42; 95% CI, 0.20-0.90; P = 0.026). Pathologically, the NAC-GS group showed significantly lower lymph node stage and less lymphatic invasion. Pathological complete response was observed in 4.0% of NAC-GS patients. DISCUSSION: Neoadjuvant chemotherapy with GS was associated with prolonged survival in resectable PDAC, potentially through lymphatic spread suppression. Pathological complete response was rare but may represent a clinically meaningful benefit of neoadjuvant treatment in selected patients.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. While curative resection offers the best chance for long-term survival, the high postoperative recurrence rate suggests a persistent need for effective perioperative therapies. We investigated a multimodal approach, combining sequential lenvatinib with transarterial chemoembolization (TACE), as a presurgical treatment (PST) for resectable HCC. METHODS: This retrospective study included 19 patients with technically resectable HCC who underwent the PST protocol followed by surgery between March 2022 and September 2024. The protocol involved four phases: Pre-TACE lenvatinib administration (Pre-LEN), TACE, Post-TACE lenvatinib administration, and surgery. We assessed the feasibility, safety, and pathological response of the protocol. Liver function was evaluated using the albumin-bilirubin (ALBI) score, modified ALBI (mALBI) grade, and tumor response was assessed using the Response Evaluation Criteria in Cancer of the Liver (RECICL). RESULTS: The PST protocol demonstrated high efficacy and safety. The median tumor reduction rate was 22.9%, and the median pathological tumor necrosis rate was 95%. The preoperative overall RECICL response was a complete response in 84.2% of patients. With a median follow-up of 22 months, the 2-year recurrence-free survival rate was 84.6%, and the overall survival rate was 100%. A significant association was found between mALBI grade and the decision to proceed with surgery at two time points: Pre-LEN (p = 0.023) and before surgery (p = 0.006). CONCLUSION: Presurgical sequential lenvatinib-TACE therapy is a feasible and safe strategy for resectable HCC. This protocol achieved a high pathological response and favorable survival outcomes, suggesting that it may mitigate the risk of early recurrence. Our findings highlight the importance of mALBI grade monitoring for patient selection and provide a rationale for larger, prospective studies.

INTRODUCTION: Neoadjuvant gemcitabine plus S-1 (GS) therapy for resectable pancreatic cancer has been shown to prolong overall survival significantly compared with upfront surgery. Herein, we report two opposite cases of patients with resectable pancreatic cancer who underwent distal pancreatectomy after neoadjuvant GS therapy. CASE PRESENTATION: In Case 1, a 49-year-old female with a 12 mm tumor in the pancreatic body (cT1N0M0, cStage IA, union for international cancer control [UICC] 8th edition) underwent two courses of neoadjuvant GS therapy followed by an open distal pancreatectomy. Pathological examination revealed no residual cancer and the patient was diagnosed with a pathological complete response (pCR) without recurrence 31 months after surgery. However, in Case 2, a 74-year-old male with a 12 mm tumor in the pancreatic body (cT1N0M0, cStage IA, UICC 8th edition) also underwent two courses of neoadjuvant GS therapy, and then a laparoscopic distal pancreatectomy was performed. Pathological examination showed invasive pancreatic ductal adenocarcinoma with a 20 mm tumor. The tumor exhibited invasion into the lumen of the splenic vein and retroperitoneal tissue (ypT1N0M0, ypStage IA, UICC 8th edition). Adjuvant chemotherapy with S-1 was started, but 4 months postoperatively, a significant rise in serum CA19-9 levels was observed with multiple hepatic metastases and portal venous tumor thrombus. Gemcitabine plus nab-paclitaxel (GnP) therapy was started, however, the tumor progressed rapidly. The patient died 6 months after surgery. CONCLUSIONS: Neoadjuvant GS therapy is potentially expected to have a significant therapeutic effect as the pCR. Nevertheless, even after surgical resection, some patients still exhibit extremely poor prognosis. Therefore, it is necessary to clarify their clinical characteristics.

The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.

BACKGROUND: Osteopenia is defined as low bone mineral density (BMD) and has been shown to be associated with outcomes of patients with various cancers. The association between osteopenia and perihilar cholangiocarcinoma is unknown. The aim of this study was to evaluate osteopenia as a prognostic factor in patients with perihilar cholangiocarcinoma. METHODS: A total of 58 patients who underwent surgery for perihilar cholangiocarcinoma were retrospectively analyzed. The BMD at the 11th thoracic vertebra was measured using computed tomography scan within one month of surgery. Patients with a BMD < 160 HU were considered to have osteopenia and b BMD ≥ 160 did not have osteopenia. The log-rank test was performed for survival using the Kaplan-Meier method. After adjusting for confounding factors, overall survival was assessed by Cox's proportional-hazards model. RESULTS: The osteopenia group had 27 (47%) more females than the non-osteopenia group (p = 0.036). Median survival in the osteopenia group was 37 months and in the non-osteopenia group was 61 months (p = 0.034). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival in patients with perihilar cholangiocarcinoma (hazard ratio 3.54, 95% confidence interval 1.09-11.54, p = 0.036), along with primary tumor stage. CONCLUSIONS: Osteopenia is associated with significantly shorter survival in patients with perihilar cholangiocarcinoma.

BACKGROUND: Despite recent progress in systemic chemotherapy, the prognosis of patients with peritoneal metastases from gastric cancer is still poor. Efficacious intraperitoneal and systemic combination chemotherapy regimens to treat patients with peritoneal metastases have recently been developed. CASE PRESENTATION: A 74-year-old man with gastric cancer T4b (transverse mesocolon) N3 M1 (peritoneum) received combination chemotherapy with intraperitoneal administration of paclitaxel, intravenous oxaliplatin, and oral S-1. Eight courses of combined chemotherapy had remarkable anti-tumor effects on the primary lesion, lymph node metastases, and peritoneal metastases. Total gastrectomy with regional lymph node dissection was performed. Pathological examination revealed no viable tumor cells in the resected specimens. After gastrectomy, the patient received 25 courses of the same chemotherapy without oxaliplatin and has no evidence of recurrence 24 months later. DISCUSSION: Therapeutic approaches including systemic chemotherapy, extended resection, and heated intraperitoneal chemotherapy have been used to treat patients with peritoneal metastases. Repeat therapy with intraperitoneal paclitaxel has been used recently. Intraperitoneal administration of paclitaxel results in prolonged retention in the peritoneal cavity with effects against peritoneal metastases. Repeated administration of paclitaxel does not cause adhesions in the peritoneal cavity. When combination chemotherapy is effective, salvage gastrectomy is a promising option with minimal morbidity and mortality. CONCLUSION: Combined chemotherapy with intraperitoneal paclitaxel and systemic chemotherapy followed by gastrectomy is a promising strategy for patients with advanced gastric cancer and peritoneal metastases.

Oxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert an analgesic effect in both humans and animals, and the results of certain animal experiments have shown that the analgesic effect of OT is partially blocked by opioid receptor antagonists. To investigate the relationship between OT and μ opioid receptor (MOR), we evaluated how OT affects MOR in vitro by performing an electrical impedance-based receptor biosensor assay (CellKey™ assay), an intracellular cAMP assay, and a competitive receptor-binding analysis by using cells stably expressing human MOR and OT receptor. In both the CellKey™ assay and the intracellular cAMP assay, OT alone exerted no direct agonistic effect on human MOR, but treatment with 10-6 M OT markedly enhanced the MOR signaling induced by 10-6 M endomorphin-1, β-endorphin, morphine, fentanyl, and DAMGO. Moreover, in the competitive receptor-binding assay, 10-6 M OT did not alter the affinity of endomorphin-1 or morphine for MOR. These results suggest that OT could function as a positive allosteric modulator that regulates the efficacy of MOR signaling, and thus OT might represent a previously unrecognized candidate analgesic agent.

A 54-year-old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin-producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high-grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.

A 41-year-old woman was admitted with upper abdominal pain, vomiting and fever. Abdominal CT scan showed a colo-duodenal fistula with inflammatory thickening of the transverse colon. The patient's general health was poor because of hypoalbuminemia and coagulopathy. Endoscopy showed a fistula at the lower duodenal angle and the stomach was filled with refluxed stool. Ileostomy and percutaneous endoscopic gastrostomy were performed at that time and a double lumen gastro-jejunostomy inserted through the gastrostomy to allow both gastric drainage and distal enteral feeding. Nutrition support was gradually converted from parenteral to enteral feeding. Colonoscopy showed stenosis of the transverse colon with a colo-colonic fistula near the stenosis. Two months later, right hemi-colectomy and closure of the colo-duodenal fistula were performed. The resected specimen showed stenosis and a fistula in the transverse colon due to Crohn's disease. The colo-colonic fistula was present and the colo-duodenal fistula had almost closed due to fibrosis. The postoperative course was uneventful and the patient was discharged after administration of infliximab. Use of a double lumen gastro-jejunostomy tube was effective in improving the patient's general condition. This therapeutic strategy allowed the safe conduct of major resection in a high-risk patient.

We report a case of hepatic choriocarcinoma in a man diagnosed at autopsy after a rapid downhill clinical course. The patient was a 49-year-old man who presented with acute right-sided abdominal pain. There were no masses palpable on physical examination. Radiographic findings showed large multi-nodular tumors mainly in the right lobe of the liver. Fludeoxyglucose-positron emission tomography scan showed uptake only in the liver, and no uptake in the testes. We initially planned to perform a liver resection for the presumed diagnosis of intra-hepatic cholangiocarcinoma. However, the tumors grew rapidly and ruptured. Multiple lung metastases rapidly developed resulting in respiratory failure, preventing liver resection or even biopsy. He died 60 d after initial presentation with no pathological diagnosis. Postmortem studies included histopathological and immunohistological examinations which diagnosed a primary choriocarcinoma of the liver. Primary hepatic choriocarcinoma is very rare but should be considered in the differential diagnosis of a liver tumor in a middle aged man. Establishing this diagnosis may enable treatment of the choriocarcinoma. Liver biopsy and evaluation of serum human chorionic gonadotropin are recommended in these patients.

OBJECTIVE: Adenosquamous carcinoma originating in the stomach is an unusual neoplasm with few existing histological studies. This study was aimed to gain insight into the histogenetic and clinicopathological characteristics of gastric cancer with squamous cell carcinoma (SCC) components. METHODS: From January 2001 to June 2010 a total of 1735 patients underwent a resection of gastric cancer. Histopathologically, eight patients had adenocarcinoma containing SCC components, in which the proportion of SCC components was above 25% of the total tumor mass in four patients. The immunohistochemical and clinicopathological characteristics of these eight patients were analyzed. RESULTS: The median survival duration was 22 months. Adenocarcinoma was present at the superficial layer of all tumors and SCC was primarily present at sites with deep invasion. Immunohistochemically, adenocarcinoma components were positive for cytokeratin (CK) 8/18/19 and CK7 in all cases. SCC components were positive for carcinoembryonic antigen and CK7 in more than 60% of patients. Expression patterns of p53 product were identical in both components. SCC components were positive for 34βE12 and adenocarcinoma components were negative for 34βE12 in all patients. CONCLUSIONS: SCC components are derived from squamous metaplasia in a pre-existing adenocarcinoma. A gastric adenocarcinoma with SCC components is associated with various patterns of metastasis and both SCC and adenocarcinoma components have the potential for metastasis. Gastric cancer with SCC components is a clinically aggressive tumor.