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Abstract Background Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. Methods This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. Trial registration This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Abstract Background The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability. Methods This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP. Results A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p

Abstract Purpose Whether surgical intervention for patients with oligometastatic recurrence can improve their post‐recurrent prognosis is unclear. In this study, we introduce a novel concept of oligometastasis in post‐surgical pancreatic ductal adenocarcinoma (PDAC) patients with hepatic recurrence, which we call “oligo‐like liver metastasis (OLLM).” Patients with OLLM have better post‐recurrence prognosis and could therefore be eligible for surgical intervention. Methods A total of 121 PDAC patients who underwent radical resection, and who had an initial and single‐organ metastasis to the liver, were analyzed. Independent prognostic factors for overall survival after recurrence (OSAR) were examined, and patients with all of these factors were defined as OLLM. The clinicopathological features and post‐recurrent prognosis of OLLM patients were evaluated. In addition, a detailed analysis using the oligo‐score, which was based on the prognostic factors, was performed. Results The prognostic analysis revealed that short recurrence‐free interval (RFI) (3 months), and three or less recurrent tumors. OLLM patients had a significantly better prognosis for OSAR than non‐OLLM patients (HR = 0.272, p

Abstract Background Peptide receptor radionuclide therapy (PRRT) serves as a novel and effective treatment option for somatostatin receptor-positive unresectable liver metastases of pancreatic neuroendocrine tumors (PNETs). However, there are few reported cases of surgical resection for initially unresectable liver metastases of PNET that were converted to resectable after PRRT. Here we report a case where PRRT and somatostatin analogs (SSAs) led to a pathological complete response of initially unresectable multiple liver metastases following PNET resection. Case presentation A 52-year-old man underwent pylorus-preserving pancreaticoduodenectomy for PNET at age 40 and subsequent hepatectomies for resectable liver metastases at 44 and 47 years of age. At age 48, a follow-up examination revealed unresectable multiple liver metastases, and PRRT with 177Lu-DOTATATE therapy was initiated. After four cycles of PRRT, most liver metastases diminished according to imaging studies, and the remaining two hepatic lesions continued to shrink with additional lanreotide. Conversion surgery for liver metastases was successfully performed, revealing no viable tumor cells in tissue specimens. Seventeen months after surgery, imaging showed no detectable residual tumor or recurrence. We present a review of the relevant literature that highlights the significance of our findings. Conclusions This rare case highlights the pathological complete response of initially unresectable multiple liver metastases achieved by PRRT and SSAs following PNET resection, suggesting their potential as a multimodality treatment option for unresectable PNET.

Subcutaneous space has been considered an attractive site for islet graft transplantation; however, the oxygen tension and vascularization are insufficient for islet graft survival. We investigated whether subcutaneous pre-implantation of a recombinant peptide (RCP) device with adipose tissue-derived stem cells (ADSCs) enhanced subcutaneous islet engraftment. RCP devices with/without syngeneic ADSCs were pre-implanted into the subcutaneous space of C57BL/6 mice. Syngeneic islets (300 or 120 islet equivalents (IEQs)) were transplanted into the pre-treated space after diabetes induction using streptozotocin. The cure rates of groups in which RCP devices were implanted four weeks before transplantation were significantly better than the intraportal transplantation group when 300 IEQs of islets were transplanted (p < 0.01). The blood glucose changes in the RCP+ADSCs-4w group was significantly ameliorated in comparison to the RCP-4w group when 120 IEQs of islets were transplanted (p < 0.01). Immunohistochemical analyses showed the collagen III expression in the islet capsule of the RCP+ADSCs-4w group was significantly enhanced in comparison to the RCP-4w and RCP+ADSCs-d10 groups (p < 0.01, p < 0.01). In addition, the number of von Willebrand factor-positive vessels within islets in the RCP+ADSCs-4w group was significantly higher than the RCP-4w group. These results suggest that using ADSCs in combination with an RCP device could enhance the restoration of the extracellular matrices, induce more efficient prevascularization within islets, and improve the graft function.

BackgroundExtrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive disease and consisted of conventional eCCA and intraductal papillary neoplasm of the bile duct (IPNB). Intraepithelial spread (IES) of cancer cells beyond the invasive area is often observed in IPNBs; however, the prevalence of IES remains to be examined in conventional eCCAs. Here, we evaluated the clinicopathological features of eCCAs according to tumor location, with a focus on the presence of IES. The IES extension was also compared among biliary tract cancers (BTCs).MethodsWe examined the prevalence and clinicopathological significance of IES in eCCAs (n=382) and the IES extension of BTCs, including gallbladder (n=172), cystic duct (n=20), and ampullary cancers (n=102).ResultsAmong the invasive eCCAs, IPNB had a higher rate of IES (89.2%) than conventional eCCAs (57.0%). Among conventional eCCAs, distal eCCAs (75.4%) had a significantly higher prevalence of IES than perihilar eCCAs (41.3%). The presence of IES was associated with a significantly higher survival rate in patients with distal eCCAs (P=0.030). Extension of the IES into the cystic duct (CyD) in distal eCCAs that cancer cells reached the junction of the CyD was a favorable prognostic factor (P