Pancreatic cancer is frequently a lethal disease with an aggressive tumour biology often presenting with non-specific symptoms. Median survival is approximately 4 months with a 5-year survival of 13%. Surveillance is recommended in individuals with familial pancreatic cancer, specific mutations, and high-risk intraductal papillary mucinous neoplasm, as they are at high risk of developing pancreatic cancer. Chemotherapy combined with surgical resection remains the cornerstone of treatment. However, only a small subset of patients are candidates for surgery. Multi-agent chemotherapy has improved survival in the palliative setting for patients with metastatic disease, as (neo)adjuvant and induction therapy have in patients with borderline resectable and locally advanced pancreatic. Given that pancreatic cancer is predicted to become the second leading cause of cancer-related death by 2030, novel therapies are urgently needed.Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by excruciating pain, which has been associated with attraction of cancer cells and their invasion of intrapancreatic sensory nerves. Neutralization of the chemokine CCL2 reduced cancer-associated pain in a clinical trial, but there have been no systematic analyses of the highly diverse chemokine families and their receptors in PDAC.We performed an open, unbiased RNA-interference screen of mammalian chemokines in co-cultures of mouse PDAC cells (K8484) and mouse peripheral sensory neurons, and confirmed findings in studies of DT8082 PDAC cells. We studied the effects of chemokines on migration of PDAC cell lines. Orthotopic tumors were grown from K8484 cells in mice, and mice were given injections of neutralizing antibodies against chemokines, antagonists, or control antibodies. We analyzed abdominal mechanical hypersensitivity and collected tumors and analyzed them by histology and immunohistochemistry to assess neural remodeling. We collected PDAC samples and information on pain levels from 74 patients undergoing resection and measured levels of CXCR3 and CCR7 by immunohistochemistry and immunoblotting.Knockdown of 9 chemokines in DRG neurons significantly reduced migration of PDAC cells towards sensory neurons. Sensory neuron-derived CCL21 and CXCL10 promoted migration of PDAC cells via their receptors CCR7 and CXCR3, respectively, which were expressed by cells in orthotopic tumors and PDAC specimens from patients. Neutralization of CCL21 or CXCL10, or their receptors, in mice with orthotopic tumors significantly reduced nociceptive hypersensitivity and nerve fiber hypertrophy and improved behavioral parameters without affecting tumor infiltration by T cells or neutrophils. Increased levels of CXCR3 and CCR7 in human PDAC specimens were associated with increased frequency of cancer-associated pain, determined from patient questionnaires.In an unbiased screen of chemokines, we identified CCL21 and CXCL10 as proteins that promote migration of pancreatic cancer cells toward sensory neurons. Inhibition of these chemokines or their receptors reduce hypersensitivity in mice with orthotopic tumors, and patients with PDACs with high levels of the chemokine receptors of CXCR3 and CCR7 had increased frequency of cancer-associated pain.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Surgical resection is the only possible cure for pancreatic cancer, it remains controversial whether extend lymphadenectomy in pancreatoduodenectomy (EPD) is better than standard lymphadenectomy in pancreatoduodenectomy (SPD). The aim of this study was to compare the efficacy of EPD with SPD for pancreatic head adenocarcinoma.A specific search of online databases including PubMed, Web of Science, Embase, and Cochrane library was conducted from January 1990 to October 2018. Relative perioperative outcomes were synthesized. Single-arm meta-analysis was also performed.A total of eight studies involving 687 (342 vs 345) patients were included for analysis in our study. The number of lymph nodes harvested [24.54 vs 13.29; weighted mean difference (WMD) -10.69, P = 0.000], operative time (469.84 min vs 354.85 min; WMD -99.09, P = 0.000), and diarrhea (postoperative three months) [45.1% vs 18.2%; odds radio (OR) 0.20, P = 0.014] were significantly higher in patients who underwent EPD than SPD. The perioperative complications (35% vs 28.8%; OR 0.79, P = 0.186), tumor size (3.27 cm vs 3.248 cm; WMD -0.11, P = 0.256), lymph node metastasis (66% vs 55.9%; OR 0.71, P = 0.105), and positive margin (10.4% vs 11.3%; OR 1.28, P = 0.392) were no significant differences between EPD group and SPD group. Extended lymphadenectomy in pancreatoduodenectomy dose not contribute to the overall survival of patients with adenocarcinoma of the pancreatic head [hazard ratio (HR) 0.95; 95% CI 0.78-1.15; P = 0.61].The update meta-analysis shows that EPD failed to improve the overall survival, may even lead to increased morbidity.Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

The aim of the present study was to investigate the feasibility of resection based on the nerve and fibrous tissue (NFT) structures around the superior mesenteric artery (SMA) for resectable pancreatic adenocarcinoma (R-PDAC) patients.NFTs around the SMA were classified into four "intensive NTFs area" with spreading the NFTs around the SMA and three SMA nerve plexus regions without branching nerves according to autopsy findings. Complete dissection of four "intensive NTFs areas" was performed by pre-exposing three SMA nerve plexus regions without branching nerves as "dissection-guiding points" with SMA nerve plexus preservation (NFT-based resection). Among 157 R-PDAC patients undergoing pancreaticoduodenectomy, surgical outcomes of 78 patients with NFT-based resection were compared with 59 patients with half-SMA nerve plexus dissection and 20 patients without NFTs dissection.In the NFT-based resection group, 76.5% had tumor involvement and metastasis in each intensive NTFs area. Operative time, blood loss, and postoperative diarrhea rate were significantly lower in NFT-based resection than in half-SMA nerve plexus group (321 vs 390 min; P < .01, 228 vs 550 mL; P < .01, 5.1% vs 15.3%; P = .04, respectively). R0 rate and median overall survival significantly improved in NFT-based resection than in non-NFT dissection group (93.6% vs 65.0%; P < .01, 49.6 vs 23.6 months, P = .01).NFT-based resection may become a novel method for R-PDAC patients.© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Superior mesenteric artery (SMA) nerve plexus (PLsma) dissection has been performed to achieve R0 resection in pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) in high‐volume centers. However, full‐extent PLsma preservation in PD is employed in our institution. The feasibility of the PLsma preservation strategy was investigated.

In pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), Prophylactic right-half dissection of the superior mesenteric artery (SMA) nerve plexus has been attempted in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In this study, we evaluated the significance of prophylactic right-half dissection of the SMA nerve plexus by extending the observation period to 5 years.From April 2014 to June 2018, 74 patients with PDAC in the pancreatic head were randomly assigned to either the dissection group, in which the right half of the nerve plexus of the SMA was dissected (n = 37) or the preservation group, in which the nerve plexus of the SMA was completely preserved (n = 37). The 5-year relapse-free survival (RFS), overall survival (OS), and incidence of diarrhea were prospectively compared between groups.The median RFS (20 vs. 16 months, P = 0.503) and OS (37.0 vs. 30.0 months, P = 0.582) did not differ significantly between the dissection and preservation groups. There was no significant difference in locoregional recurrence (27.0% vs. 37.8%, P = 0.320) or distant metastasis (64.9% vs. 83.0%, P = 0.451). Postoperative diarrhea occurred in 64.9% and 62.2% of the cases in the dissection and preservation groups, respectively (P = 0.809).Prophylactic right half dissection of the SMA nerve plexus did not improve the RFS or OS.© 2025. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.

Open pancreatoduodenectomy with vein resection (OPD-VR) is now standard of care in patients who responded to neoadjuvant therapies. Feasibility of robotic pancreatoduodenectomy (RPD) with vein resection (RPD-VR) was shown, but no study provided a detailed description of the technical challenges associated with this formidable operation. Herein, we describe the trips and tricks for technically successful RPD-VR.The vascular techniques used in RPD-VR were borrowed from OPD-VR, as well as from our experience with robotic transplantation of both kidney and pancreas. Vein resection was classified into 4 types according to the international study group of pancreatic surgery. Each type of vein resection was described in detail and shown in a video.Between October 2008 and November 2021, a total of 783 pancreatoduodenectomies were performed, including 233 OPDs-VR (29.7%). RPD was performed in 256 patients (32.6%), and RPDs-VR in 36 patients (4.5% of all pancreatoduodenectomies; 15.4% of all pancreatoduodenectomies with vein resection; 14.0% of all RPDs). In RPD-VR vein resections were: 4 type 1 (11.1%), 10 type 2 (27.8%), 12 type 3 (33.3%) and 10 type 4 (27.8%). Vascular patches used in type 2 resections were made of peritoneum (n = 8), greater saphenous vein (n = 1), and deceased donor aorta (n = 1). Interposition grafts used in type 4 resections were internal left jugular vein (n = 8), venous graft from deceased donor (n = 1) and spiral saphenous vein graft (n = 1). There was one conversion to open surgery (2.8%). Ninety-day mortality was 8.3%. There was one (2.8%) partial vein thrombosis, treated with heparin infusion.We have reported 36 technically successful RPDs-VR. We hope that the tips and tricks provided herein can contribute to safer implementation of RPD-VR. Based on our experience, and according to data from the literature, we strongly advise that RPD-VR is performed by expert surgeons at high volume centers.© 2023. The Author(s).

Pancreaticoduodenectomy (PD) is the standard surgical procedure for treating pancreatic head cancers. Considerable knowledge of proximal jejunal and pancreatic vein anatomy is a prerequisite for performing PD surgery safely, yet there appear to be no detailed descriptions of first and second jejunal vein (J1V, J2V) anatomy available in the literature.Adults with hepatobiliary-pancreatic disease underwent multidetector-row computed tomography with intravenous contrast (n = 155), and SYNAPSE 3D (Fujifilm Medical, Tokyo, Japan) was used to generate 3D-CT images.In 84% of patients, J1V and J2V formed a common trunk (FJT). There were three patterns of branches, related to the presence or absence of FJT formation and the anatomical relationships between the superior mesenteric artery (SMA) and the jejunal veins, as follows: Type 1 (n = 98, 63%) characterized by an FJT located dorsal to SMA; Type 2 (n = 32, 21%), where the FJT was located ventral to the SMA; and Type 3 (n = 25, 16%), where J1V and J2V each drained separately into the SMV.J1V and J2V usually formed an FJT, and separate J1V and J2V drainage into the SMV was uncommon. Preoperative information on individual patient venous anatomy would increase the safety of the PD procedure.© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Tumors of the neck of the pancreas may involve the superior mesenteric and portal veins as well as the termination of the splenic vein. This presents a difficult problem since the pancreas cannot be transected through the neck as is standard in a Whipple procedure. Here, we present our method of resecting such tumors, which we term "Whipple at the Splenic Artery (WATSA)".The superior mesenteric and portal veins are isolated below and above the pancreas, respectively. The pancreas and splenic vein are divided just to the right of the point that the splenic artery contacts the superior border of the pancreas. This plane of transection is approximately 2 cm to the left of the pancreatic neck and away from the tumor. The superior mesenteric artery is cleared from the left side of the patient. With the specimen remaining attached only by the superior mesenteric and portal veins, these structures are clamped and divided. Reconstruction is performed with or without a superficial femoral vein graft. The splenic vein is not reconstructed.Ten cases have been performed to date without mortality. We have previously shown that the pattern of venous collateral development following occlusion of the termination of the splenic vein in the manner described is not similar to that of cases of sinistral (left sided) portal hypertension.Whipple at the splenic artery (WATSA) is a safe method for resection of tumors of the neck of the pancreas with vein involvement. It should be performed in high-volume pancreatic surgery centers.

该文围绕腹腔镜胰十二指肠切除术中血管处理策略展开阐述。开展腹腔镜胰十二指肠切除术后应熟悉胰头十二指肠切除手术重点区域血管解剖并且通过术前三维重建了解血管变异。提出应用"一轴二面四区"及"危险三角"的解剖概念处理胰十二指肠血管。术中注意避免动脉内膜损伤和静脉撕脱，尤其注意腹腔镜下血管的"帐篷效应"，避免血管损伤。手术团队应增强手术配合意识，及时处理术中意外出血，避免灾难性大出血的发生。严密监测术后出血和早期积极处理，可减少术后严重并发症的发生。

The results of laparoscopic pancreaticoduodenectomy combining with mesentericoportal vein resection and reconstruction (LPD-MPVRs) for pancreatic head adenocarcinoma are rarely reported. The aim of present study was to explore the short- and long-term outcomes of different type of LPD-MPVRs.Patients who underwent LPD-MPVRs in 14 Chinese high-volume pancreatic centers between June 2014 and December 2020 were selected and compared.In total, 142 patients were included and were divided into primary closure (n = 56), end-end anastomosis (n = 43), or interposition graft (n = 43). Median overall survival (OS) and median progress-free survival (PFS) between primary closure and end-end anastomosis had no difference (both P > 0.05). As compared to primary closure and end-end anastomosis, interposition graft had the worst median OS (12 months versus 19 months versus 17 months, P = 0.001) and the worst median PFS (6 months versus 15 months versus 12 months, P < 0.000). As compared to primary closure, interposition graft had almost double risk in major morbidity (16.3 percent versus 8.9 percent) and about triple risk (10 percent versus 3.6 percent) in 90-day mortality, while End-end anastomosis had only one fourth major morbidity (2.3 percent versus 8.9 percent). Multivariate analysis revealed postoperation hospital stay, American Society of Anesthesiologists (ASA) score, number of positive lymph nodes had negative impact on OS, while R0, R1 surgical margin had protective effect on OS. Postoperative hospital stay had negative impact on PFS, while primary closure, end-end anastomosis, short-term vascular patency, and short-term vascular stenosis positively related to PFS.In LPD-MPVRs, interposition graft had the worst OS, the worst PFS, the highest rate of major morbidity, and the highest rate of 90-day mortality. While there were no differences in OS and PFS between primary closure and end-end anastomosis.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.