Clinical characterization of patients with gBRCA1/2 mutation-positive unresectable pancreatic cancer: a multicenter prospective study.

BACKGROUND: Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan. METHODS & RESULTS: In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for ˃4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0-9.2). CONCLUSIONS: The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.

Clinical benefit of early precut sphincintroterotomy for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography.

OBJECTIVES: A precut procedure is sometimes required for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP). However, it is unclear whether the biliary access rate has improved for early precut procedures compared to conventional techniques. This study aimed to identify the benefit of early precut sphincterotomy in cases showing difficult biliary access. METHODS: Between April 2017 and August 2021, consecutive patients who underwent precutting for difficult biliary cannulation were retrospectively enrolled. The outcomes of early (≤ 10 min from start of cannulation) and delayed (> 10 min) precut groups were evaluated. All adverse events were defined according to Cotton criteria. RESULTS: A total of 70 patients were enrolled in this study. The biliary cannulation rate for a first ERCP was significantly higher in the early compared to delayed precut group (95% vs. 73.3%; P = 0.015). A difference in overall cannulation rate between the two groups was not observed (97.5% vs. 83.3%; P > 0.05). Significantly higher rates of prophylactic pancreatic stents were described in the delayed compared to early precut group (36.7% vs. 12.5%; P = 0.009). Significant differences in the frequency of pancreatitis, bleeding, penetration, and perforation were not noted between the two groups. Overall, the success rate was statistically significant between the experienced and less experienced endoscopists (87.2% vs. 63.9%; P = 0.017). CONCLUSIONS: Early precutting within 10 min from the start of cannulation in ERCP is safe and effective in cases with a difficult biliary cannulation, and can improve the biliary cannulation rate.

Inutility of endoscopic sphincterotomy to prevent pancreatitis after biliary metal stent placement in the patients without pancreatic duct obstruction.

Background: The incidence of post-ERCP pancreatitis (PEP) has been reported to be significantly higher in patients without main pancreatic duct (MPD) obstruction who undergo transpapillary biliary metal stent (MS) placement than in those with ordinary ERCP setting.Objective: To evaluate the benefit of endoscopic sphincterotomy (ES) prior to MS placement in preventing PEP in patients with distal malignant biliary obstruction (MBO) without MPD obstruction.Materials and methods: In total, 160 patients who underwent initial MS placement for MBO were enrolled. Eighty-two patients underwent ES immediately prior to MS placement, whereas 78 underwent MS placement without ES. An inverse probability of treatment weighting method was adopted to adjust the differences of the patients' characteristics. The primary outcome was the incidence of PEP. The secondary outcomes included the incidence of other adverse events (bleeding, cholangitis, perforation and stent dislocation) and time to recurrent biliary obstruction.Results: The incidence of PEP was 26.8% in the ES and 23.1% in the non-ES (unadjusted odds ratio [OR] [95%CI]: 1.22, [0.60-2.51], adjusted OR [95%CI]: 1.23, [0.53-2.81], p = .63). Logistic-regression analysis revealed no factors that could be attributed to the occurrence of PEP. The incidence of other adverse events was not different between the groups. The median time to recurrent biliary obstruction was 131 (2-465) days and 200 (4-864) days in the ES and non-ES, respectively (p = .215).Conclusions: ES prior to MS placement for patients with distal MBO without MPD obstruction does not reduce the incidence of PEP.

[Good's syndrome developing hemophagocytic lymphohistiocytosis following thymectomy].

This report presents the case of a 68-year-old female patient previously diagnosed with thymoma by her local doctor. She was referred to our hospital for surgery, and the thymoma was removed and diagnosed as a World Health Organization (WHO) classification type AB thymoma. After surgery, she experienced general malaise, a loss of appetite, and weight loss, so she visited our hospital in May 2019. A blood test showed hypogammaglobulinemia and low B lymphocytes. A bone marrow examination revealed no morphological abnormalities. Flow cytometric analysis indicated a marked decrease in both the B cell-related surface markers CD19 and CD20 and the T cell-related surface marker CD4, and the CD4/CD8 ratio was also low. She was diagnosed with Good's syndrome, and immunoglobulin replacement therapy was administered. She subsequently developed hemophagocytic lymphohistiocytosis (HLH) due to infection and was treated according to the HLH2004 protocol, but she finally succumbed to multiple organ damage as a result of sepsis. Given that Good's syndrome is associated with both humoral and cellular immune dysfunctions, affected patients tend to develop severe infections and have a poor prognosis. In such cases, early detection, regular immunoglobulin replacement therapy, and infection prevention therapies are important.

Long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography using balloon-assisted enteroscopy for anastomotic stenosis of choledochojejunostomy/pancreaticojejunostomy.

BACKGROUND AND AIM: Data on long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography (ERCP) using balloon-assisted enteroscopy (BAE) for choledochojejunal anastomotic stenosis (CJS) or pancreaticojejunal anastomotic stenosis (PJS) remain limited. We retrospectively assessed the long-term results of patients who achieved clinical success using BAE for CJS and PJS. METHODS: Patients who achieved technical and clinical success for CJS or PJS by BAE-ERCP and were followed up for more than 6 months after the initial BAE-ERCP therapy were retrospectively identified at 11 Japanese institutions. The primary end-point was CJS or PJS recurrence rates. The secondary end-points were initial therapy details, initial therapy complications, and CJS or PJS recurrence treatment details. We also evaluated restenosis-associated factors. RESULTS: From September 2008 to December 2015, 67 patients (CJS, 61; PJS, six) were included. The overall CJS and PJS recurrence rates were 34.4% and 33.3%, respectively. The 1-year CJS recurrence rate was 18.5% (95% confidence interval, 10.7-31.0). Of all the patients, 88.1% underwent balloon dilation at the anastomotic stenosis site; stent placement was performed in 15 of 67 patients (22.4%). The complication rate was 8.2% in CJS and 0% in PJS. In patients who underwent balloon dilation, "remaining waist" was significantly associated with CJS recurrence after anastomotic balloon dilation (P = 0.001). CONCLUSIONS: The long-term outcomes of BAE-ERCP were comparable with those of percutaneous transhepatic treatment or surgical re-anastomosis.

[Significance of upper and lower gastrointestinal endoscopy for screening small intestinal lesions in non-Hodgkin's lymphoma].

The gastrointestinal tract is a common site for the occurrence of non-Hodgkin's lymphoma (NHL). NHL with gastrointestinal lesions may lead to clinically relevant intestinal complications such as obstruction, perforation, and exsanguination during the course of the disease. Consequently, patients with NHL are often examined by means of upper and lower gastrointestinal endoscopy at the initial visit. There are no clear guidelines regarding which patients should undergo capsule endoscopy (CE) and balloon enteroscopy for detecting small intestinal lesions. We retrospectively examined the feasibility of detecting small intestinal lesions in NHL using upper and lower gastrointestinal endoscopy. Between January 2007 and October 2015, 198 patients with primary NHL were admitted to our hospital. We collected data from 51 patients with NHL with gastrointestinal lesions diagnosed through upper and lower gastrointestinal endoscopy, CE, or double balloon enteroscopy (DBE). We chosed these cases that gastrointestinal lesions was doubted by an examination for image. Nineteen of these patients presented with lymphoma at the duodenal bulb/descending part when examined by upper gastrointestinal endoscopy and at the distal ileum when examined by lower gastrointestinal endoscopy. Ectopic jejunoileal lymphoma was simultaneously detected in 13 of the 19 patients (68.4%) through the use of CE or DBE. Conversely, of the 32 patients who did not exhibit lesions at the duodenal bulb/descending part or at the distal ileum, 6 patients (18.8%) presented with small intestinal lesions, indicating a smaller percentage compared to the patients with ectopic jejunoileal lymphoma. Based on these findings, a proactive search for small intestinal lesions using CE or DBE is recommended in patients with NHL presenting with lymphoma at the duodenal bulb/descending part or at the distal ileum, as examined using both upper and lower gastrointestinal endoscopy during the initial visit.

Randomized trial comparing a side-port needle and standard needle for EUS-guided histology of pancreatic lesions.

BACKGROUND AND AIMS: A side-port needle has been developed to improve diagnostic accuracy by obtaining more cellular material during EUS-guided FNA (EUS-FNA). We compared the accuracy rate of histology and the quality of histologic specimens from 22-gauge (G) side-port and standard needles for EUS-FNA of a solid pancreatic mass in a multicenter, prospective, randomized control trial. METHODS: Between January 2013 and September 2013, 160 consecutive patients with a suspected solid pancreatic mass at 5 tertiary referral centers were enrolled. Patients were randomized to the 22G side-port needle or 22G standard needle group. The primary endpoint was the diagnostic accuracy of histology. Secondary endpoints were the quality of the histologic specimen (quantity of tissue, degree of GI contamination, and amount of blood). RESULTS: An analysis of 154 patients (side-port, 76, vs standard, 78) was performed. Six patients were excluded because of no pancreatic mass on EUS. There was no significant difference in the rate of diagnostic accuracy of histology (side-port, 87% [66/76], vs standard, 82% [64/78]; P = .51). Samples that enabled histologic interpretation were obtained in 64% (47/73) and 43% (33/77) of patients from the side-port and standard groups, respectively (P = .009). No significant difference was seen in the degree of GI contamination and amount of blood between groups. CONCLUSIONS: There was no significant difference in the accuracy rate of histology between needle types. The side-port needle was superior to the standard needle in terms of obtaining samples that enabled histologic interpretation.

RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells.

BACKGROUND: ST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo. METHODS: Gastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot. RESULTS: ST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b. CONCLUSION: ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.

No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a serious complication. Rectal diclofenac (100 mg) has been shown to reduce the incidence of pancreatitis; however, this dosage form is unavailable in several countries. AIMS: We aimed to investigate the preventive effect of oral diclofenac on pancreatitis after ERCP in a multicenter, randomized, prospective, placebo-controlled, double-blind trial. METHODS: Patients undergoing a first ERCP in seven high-volume centers between July 2012 and August 2014 were considered eligible. Participants were administered oral diclofenac (50 mg) or placebo before and after ERCP. The primary endpoint was the incidence of pancreatitis. A subgroup analysis was performed for patients at high or low risk of pancreatitis. Secondary endpoints were pancreatic enzyme levels (amylase and lipase). RESULTS: We initially enrolled 430 patients (216 in the diclofenac and 214 in the placebo group), and 23 were excluded after randomization. The overall incidence of pancreatitis was 9.8 % (20/205) and 9.4 % (19/202) in the diclofenac and placebo groups, respectively (p = 0.90). The incidence of pancreatitis was 20.3 % (13/64) and 21.3 % (13/61) in patients at high risk of pancreatitis (p = 0.78) and 5.0 % (7/141) and 4.3 % (6/141) in patients at low risk of pancreatitis in the diclofenac and placebo groups (p = 0.94), respectively. There were no significant differences in serum amylase and lipase levels between the two groups before and 24 h after ERCP. CONCLUSIONS: Oral administration of diclofenac before and after ERCP showed no benefit in the prevention of pancreatitis. CLINICAL TRIALS REGISTRY NO: UMIN000008109.

Pancreatic metastasis from a solitary fibrous tumor of the central nervous system.

CONTEXT: Solitary fibrous tumor of the central nervous system is uncommon, with only around 200 reported cases. Further, extracranial metastasis is extremely rare, and only 5 cases of hematogenous metastases have been reported so far. To the best of our knowledge, there have been no reports of solitary fibrous tumor of the central nervous system metastasizing to the pancreas. CASE REPORT: A 62-year-old woman was referred for evaluation of a pancreatic mass, which was strongly suspected to be a neuroendocrine tumor. However, the histological findings and immunohistochemical profile indicated the presence of a solitary fibrous tumor. Because the medical history revealed previous transcranial resection for intracranial meningioma 16 years ago, we conducted a pathological review of the brain specimen obtained by the first operation and found that it had the same histology and immunohistochemical profile as the current endoscopic ultrasound-guided fine-needle aspiration specimen. Consequently, the final diagnosis, on the basis of the brain specimen, was changed from meningioma to solitary fibrous tumor of the central nervous system, and the pancreatic mass was diagnosed as metastasis from solitary fibrous tumor of the central nervous system. The patient underwent middle pancreatectomy; the pancreatic specimen also had the same histology and immunohistochemical profile as the brain specimen. CONCLUSION: Histological findings and immunohistochemical profile obtained by EUS-FNA are invaluable for the correct diagnosis to avoid excessive surgical procedures.

Tissue acquisition for comprehensive genomic profiling of gallbladder cancer using a forward-viewing echoendoscope in a patient who underwent Roux-en-Y reconstruction.

A 50-year-old man with a history of total gastrectomy, distal pancreatectomy, splenectomy, and Roux-en-Y reconstruction was admitted to our hospital with a gallbladder tumor that had infiltrated the liver and abdominal wall. Because malignant cells were not collected during the percutaneous biopsy, we planned to perform an endoscopic ultrasound-guided fine-needle biopsy with a 22-G Franseen needle using a forward-viewing echoendoscope. Using intermittent manual compression, the forward-viewing echoendoscope reached the duodenum under fluoroscopic guidance. Endoscopic ultrasound-guided fine-needle biopsy was performed using a 22-G needle and 20-mL syringe and yielded a sufficient specimen with a single puncture. Malignant cells were promptly identified during on-site evaluation. The composition of the specimen (> 20% cancer cells and tissue area exceeding 25 mm2) enabled comprehensive genomic profiling. Subsequently, high-tumor mutational burden was diagnosed based on comprehensive genomic profiling, and pembrolizumab was initiated as a second-line therapy. Even in cases involving Roux-en-Y reconstruction, endoscopic ultrasound-guided fine-needle biopsy using a forward-viewing echoendoscope can result in collection of a high-quality specimen.

Efficacy and safety of endoscopic ultrasound-guided gallbladder drainage without dilation by using a 0.035-inch stiff guidewire.

Endoscopic ultrasound-guided gallbladder drainage for patients with cholecystitis and high surgical risk is commonly performed by dilating the fistula before inserting the delivery sheath; however, this carries an increased risk of peritonitis. To overcome this problem, we developed a new technique that did not require dilation, using a 0.035-inch stiff guidewire, and retrospectively evaluated the efficacy and safety of this technique. This retrospective case series report collected data on non-surgical patients who underwent endoscopic ultrasound-guided gallbladder drainage for various indications at Steel Memorial Muroran Hospital between November 2020 and October 2022. A total of 71 patients were included (mean age 83 ± 7.6 years; 33 women and 38 men). Breakthrough of the delivery sheath without dilation of the fistula was successful in 97.2% (n = 69) of patients. The success rate of stent placement was 98.6% (n = 70), as was the clinical success rate. Complications occurred in 2.8% (n = 2) of patients. Early and late adverse events occurred in 2.8% (n = 2) and 12.7% (n = 9) of patients, respectively. The mean procedure time was 24.8 ± 9.3 min. If a 0.035-inch stiff guidewire is used, the dilation procedure can be omitted in the endoscopic ultrasound-guided gallbladder drainage using self-expandable metal stents.

Risk factors for recurrent biliary obstruction following endoscopic biliary stenting in patients with unresectable ampullary cancer: A multicenter retrospective study.

OBJECTIVES: Unresectable ampullary cancer (AC) is a rare disease entity. The risk factors for recurrent biliary obstruction (RBO) following endoscopic biliary stenting (EBS) for unresectable AC remain unknown. In this study we aimed to evaluate the cumulative RBO rate and to identify risk factors for RBO following palliative EBS in patients with unresectable AC. METHODS: This multicenter retrospective observational study enrolled consecutive patients with unresectable AC who had undergone palliative EBS between April 2011 and December 2021. The cumulative rate of and risk factors for RBO following palliative EBS were evaluated via multivariate analysis. RESULTS: The study analysis comprised 107 patients with a median age of 84 years (interquartile range 79-88 years). Plastic stents (PSs) and self-expandable metal stents (SEMSs) were placed in 53 and 54 patients, respectively. Functional success was accomplished in 104 (97.2%) patients. Of these, RBO occurred in 62 (59.6%) patients, with obstruction and complete/partial migration occurring in 47 and 15 patients, respectively. The median time to RBO was 190 days. Multivariate analysis showed that PS was associated with a higher rate of RBO compared to SEMS (hazard ratio [HR] 2.48; P < 0.01) and that the presence of common bile duct stones/sludge immediately after EBS was an independent risk factor for RBO (HR 1.99; P = 0.04). CONCLUSIONS: The use of SEMS compared to PS during EBS reduced the time to RBO in patients with unresectable AC. Common bile duct stones/sludge immediately after EBS was a risk factor for RBO.

Rapid on-site evaluation by endosonographer during endoscopic ultrasound-guided fine needle aspiration for pancreatic solid masses.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established diagnostic method for patients with suspected pancreatic ductal carcinoma. Rapid on-site evaluation (ROSE) has been reported to improve the accuracy. However, an on-site cytopathologist is not routinely available in many institutions. One of the solutions may be ROSE by endosonographer. The aim was to examine whether diagnostic accuracy increases through ROSE by endosonographer using our cytological criteria. METHODS: Patients who underwent EUS-FNA of solid pancreatic masses from January 2006 to August 2009 (n = 53, period 1) and September 2009 to April 2011 (n = 85, period 2) were retrospectively identified. Before initiating ROSE at the start of period 2, two endosonographers underwent training for cytological interpretation, which was focused on four cytological features of pancreatic ductal carcinoma: anisonucleosis, nuclear membrane irregularity, overlapping, and enlargement. During EUS-FNA in period 2, endosonographers classified the Diff-Quik smears under three atypical grades and evaluated the adequacy. All diagnoses were made by one pathologist without knowledge of clinical information. RESULTS: The rate of "inconclusive" diagnoses, interpreted as "suspicious," "atypical," and "inadequate for diagnosis" was reduced from 26.4% in period 1 to 8.2% in period 2 (P = 0.004). Moreover, diagnostic accuracy was increased from 69.2% in period 1 to 91.8% in period 2 (P < 0.001). CONCLUSIONS: This cytological grading system used in ROSE by endosonographers is invaluable for the diagnosis of pancreatic solid masses.

Newly designed plastic stent for endoscopic placement above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

BACKGROUND: Plastic stent (PS) occlusion occurs as a result of bacterial adherence to the stent's inner wall. To retain the bacteriological barrier, placing a PS above the sphincter of Oddi ('inside stent') has been investigated. We designed a new PS (inside stent with thread [IT] stent) with attachable nylon thread for use as an inside stent and for easy retrieval. The present study evaluated the IT stent's technical feasibility and efficacy for malignant hilar biliary obstruction. PATIENTS AND METHODS: A total of 26 consecutive patients with unresectable malignant hilar biliary obstruction underwent placement of IT stents from August 2007 to February 2011. IT stents were placed across the strictures without sphincterotomy to achieve bilateral drainage. RESULTS: The overall technical success rate of the IT stent was 100% for one session. Multiple IT stents were inserted in 25 cases(two stents in 15 patients, three stents in 10 patients). No stent-related early complications occurred. The functional success rate was 92% (24/26). The rate of reintervention because of stent malfunction was 50% (13/26). In all 16 patients who underwent stent removal, IT stents were easily retrieved using the nylon thread. According to Kaplan-Meier analysis, the median stent patency period was 136 days. CONCLUSION: IT stents for endoscopic placement above the sphincter of Oddi can be used safely and effectively for malignant hilar biliary obstruction.

Atypical Pseudo-Meigs' Syndrome without Pleural Effusion Due to Ovarian Metastasis from Sigmoid Colon Cancer.

We herein report a case of atypical pseudo-Meigs' syndrome without pleural effusion. A 46-year-old woman was diagnosed with an ovarian tumor and sigmoid colon cancer with massive ascites. She underwent surgical resection of the sigmoid colon and bilateral salpingo-oophorectomy. The pathological diagnosis was sigmoid colon cancer with ovarian metastasis. A few days after the operation, the massive ascites disappeared. Immunostaining for vascular endothelial growth factor (VEGF) suggested its overproduction was involved in the development of the ascites. Although cases of pseudo-Meigs' syndrome without pleural effusion are rare, reporting such cases will facilitate the choice of more appropriate treatment strategies in future.

Detailed Clinical Characteristics, Interventions, and Long-Term Outcomes of Patients With Gastric Cancer Who Received the Best Supportive Care Without Any Anticancer Treatment.

Background: Due to the lack of studies, the long-term prognoses of unfit patients with gastric cancer (GC) who did not receive any aggressive cancer treatment (best supportive care [BSC] cases) remain unclear, especially for those with potentially curable GC. We conducted this observational study to capture the real-world data of characteristics and outcomes for BSC cases. Method: Consecutive clinical records of patients with GC diagnosed at Steel Memorial Muroran Hospital from January 2017 to December 2021 were analyzed. Result: Of 481 patients diagnosed with GC, 91 (18.9%) were BSC cases. The median overall survival (OS) was 12.4, 8.3, and 2.5 months for clinical stage (cStage) I, II-III, and IV, respectively. Patients with potentially curable GC (cStage I-III) had significantly longer OS than those with incurable disease (cStage IV), with a hazard ratio for death of 0.29 (95% confidence interval: 0.18-0.47). Conclusion: Our report provides useful information for decision-making for unfit patients with GC in daily clinical practice.

HOPS-R01 phase II trial evaluating neoadjuvant S-1 therapy for resectable pancreatic adenocarcinoma.

Although neoadjuvant therapy (Nac) is recommended for high-risk resectable pancreatic cancer (R-PDAC), evidence regarding specific regimes is scarce. This report aimed to investigate the efficacy of S-1 Nac for R-PDAC. In a multicenter phase II trial, we investigated the efficacy of Nac S-1 (an oral fluoropyrimidine agent containing tegafur, gimeracil, and oteracil potassium) in R-PDAC patients. The protocol involved two cycles of preoperative S-1 chemotherapy, followed by surgery, and four cycles of postoperative S-1 chemotherapy. Two-year progression-free survival (PFS) rates were the primary endpoint. Overall survival (OS) rates and median survival time (MST) were secondary endpoints. Forty-nine patients were eligible, and 31 patients underwent resection following Nac, as per protocol (31/49; 63.3%). Per-protocol analysis included data from 31 patients, yielding the 2-year PFS rate of 58.1%, and 2-, 3-, and 5-year OS rates of 96.8%, 54.8%, and 44.0%, respectively. MST was 49.2 months. Intention-to-treat analysis involved 49 patients, yielding the 2-year PFS rate of 40.8%, and the 2-, 3-, and 5-year OS rates of 87.8%, 46.9%, and 33.9%, respectively. MST was 35.5 months. S-1 single regimen might be an option for Nac in R-PDAC; however, the high drop-out rate (36.7%) was a limitation of this study.