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Background: Surgical resection is a part of the treatment pathways for the management of pancreatic cancer with arterial involvement. Arterial resection in this context is however not widely supported due to the paucity and diversity of the reported evidence in the literature. The aim of this systematic review is the presentation and analysis of the current evidence in the field. Methods: A systematic literature search of PubMed, MEDLINE and the Cochrane Library was performed for eligible studies, following the PRISMA guidelines. Information on baseline characteristics, peri-operative outcomes, survival outcomes and histopathological findings were extracted for pooling and analysis. Results: Eight studies with a total of 170 patients were included in the analysis. One hundred and thirty-five patients had a pancreaticoduodenectomy (PD) and 35 had a total pancreatectomy (TP) with arterial resection. Perioperative morbidity was 43.5% and mortality was 4.5%. Median overall survival (OS) was 12.7 months (range, 10.5-22.2 months). Overall 3- and 5-year survival for this cohort was reported at 6.6% (range, 0-42.4%) and 3.3% (range, 0-6.6%) respectively. Resection margins were clear (R0) in a median of 75% of patients. Only a median of 45% of patients received neo-adjuvant chemotherapy. Conclusions: Arterial resection can be performed with an acceptable peri-operative morbidity and mortality. However, survival outcomes are still not convincing and future efforts should concentrate on patient and disease biology selection.

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Background: Arterial resection (AR) during pancreatectomy for curative R0 resection of pancreatic ductal adenocarcinoma (PDAC) remains a controversial procedure with high morbidity. Objective: To investigate the feasibility and oncological outcomes of pancreatectomy combined with AR at a high-volume center for pancreatic surgery. Methods: We retrospectively analyzed our experience in PDAC patients, who underwent pancreatic resection with AR and/or venous resection (VR) between 2007 and 2021. Results: In total 259 PDAC patients with borderline resectable (n = 138) or locally advanced (n = 121) PDAC underwent vascular resection during tumor resection. From these, 23 patients had AR (n = 4 due to intraoperative injury, n = 19 due to suspected arterial infiltration). However, 12 out of 23 patients (52.2%) underwent simultaneous VR including 1 case with intraoperative arterial injury. In comparison, 11 patients (47.8%) underwent AR only including 3 intraoperative arterial injury patients. Although the operation time and bleeding rate of patients with AR were respectively longer and higher than in VR, no significant difference was detected in postoperative complications between VR and AR (P = 0.11). The final histopathological findings of PDAC patients were similar, including M stage, regional lymph node metastases, and R0 margin resection. The mortality of the entire cohort was 6.2% (16/259), with a tendency to increase mortality in the AR cohort, yet without statistical significance (VR: 5% vs AR: 21.1%; P = 0.05). Although 19 (82.6%) patients had PDAC in the final histopathology, only 6 were confirmed to have infiltrated arteria. The microscopic distribution of PDAC in these infiltrated arterial walls on hematoxylin-eosin staining was classified into 3 patterns. Strikingly, the perivascular nerves frequently exhibited perineural invasion. Conclusions: AR can be performed in high-volume centers for pancreatic surgery with an acceptable morbidity, which is comparable to that of VR. However, the likelihood of arterial infiltration seems to be rather overestimated, and as such, AR might be avoidable or replaced by less invasive techniques such as divestment during PDAC surgery.

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PURPOSE: Tumors with involvement of common hepatic and gastroduodenal arteries (CHA and GDA) or GDA and the proper hepatic artery (PHA) are traditionally considered nonresectable. We have devised a new procedure that includes pancreaticoduodenectomy with preoperative hepatic artery embolization (PD-HAE) to facilitate an R0 resection of tumors involving the hepatic arteries without vascular anastomoses and complete sacrifice of normal hepatic arterial blood supply. METHODS: To allow resection of the hepatic arteries, preoperative embolization of the PHA was performed to induce an increased collateral arterial blood flow from the periphery of the liver, far from the hepatic hilum 10-14 days prior to the operation. Between May 1, 2017 and December 31, 2019, eight patients with ductal adenocarcinoma were operated with the PD-HAE procedure. RESULTS: The embolizations were uneventful apart from a transient marginal elevation of alanine aminotransferase in three patients. All patients had N disease with perineural invasion of tumor cells around the adventitia of the artery and severe perivascular inflammation. An R0 resection (> 1.0 mm to all resection margins) was obtained in six patients (75%). Mean hospital stay was 12 days. Median survival was 23 months (95% CI: 19.5-26.5 months). Six patients (75%) are still alive 11 to 36 months after the operation. There was perioperative fatality, and morbidity was comparable to standard pancreaticoduodenectomy. CONCLUSION: PD-HAE is a safe procedure and may provide the opportunity for curative resection in otherwise unresectable patients. However, larger studies are needed to evaluate this procedure.

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Objective: This study aims to summarize our single-center initial experience in laparoscopic pancreatic operation (LPO) combined with hepatic arterial resection and reconstruction, as well as to demonstrate the feasibility, safety, and key surgical procedure for LPO. Methods: We retrospectively analyzed 7 patients who had undergone LPO combined with hepatic arterial resection and reconstruction in our center from January 2021 to December 2022. The clinical data of these 7 patients were collected and analyzed. Results: In our case series, two patients underwent passive arterial resection and reconstruction due to iatrogenic arterial injury, and five patients underwent forward arterial resection and reconstruction due to arterial invasion. The arterial anastomosis was successful in 5 cases, including 2 cases of end-to-end in situ and 3 cases of arterial transposition, and the vascular reconstruction time was 38.28 ± 15.32 min. There were two conversions to laparotomy. The postoperative recovery of all patients was uneventful, with one liver abscess (Segment 4) and no Clavien III-IV complications. We also share valuable technical feedback and experience gained from the initial practice. Conclusions: Based on the surgeon's proficiency in open arterial resection and reconstruction and laparoscopic technique. This study demonstrated the feasibility of total laparoscopic hepatic arterial resection and reconstruction in properly selected cases of arterial involvement or iatrogenic arterial injury. Our initial experience provides valuable information for laparoscopic pancreas surgery with arterial resection and reconstruction.

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Pancreatic ductal adenocarcinoma remains a global health challenge and is predicted to soon become the second leading cause of cancer death in developed countries. Currently, surgical resection in combination with systemic chemotherapy offers the only chance of cure or long-term survival. However, only 20% of cases are diagnosed with anatomically resectable disease. Neoadjuvant treatment followed by highly complex surgical procedures has been studied over the last decade with promising short- and long-term results in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). In recent years, a wide variety of complex surgical techniques that involve extended pancreatectomies, including portomesenteric venous resection, arterial resection, or multi-organ resection, have emerged to optimize local control of the disease and improve postoperative outcomes. Although there are multiple surgical techniques described in the literature to improve outcomes in LAPC, the comprehensive view of these strategies remains underdeveloped. We aim to describe the preoperative surgical planning as well different surgical resections strategies in LAPC after neoadjuvant treatment in an integrated way for selected patients with no other potentially curative option other than surgery.

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Background: The artery involvement explains the majority of primary unresectability of non-metastatic pancreatic cancer patients and both arterial resection and artery-sparing dissection techniques are utilized in curative-intent pancreatectomies for artery-involving pancreatic cancer (ai-PC) patients. Methods: This narrative review summarized the history of resectability evaluation for ai-PC and attempted to interpret its current pitfalls that led to the divergence of resectability prediction and surgical exploration, with a focus on the rationale and the surgical outcomes of the sub-adventitial divestment technique. Results: The circumferential involvement of artery by tumor currently defined the resectability of ai-PC but insufficient to preclude laparotomy with curative intent. The reasons behind could be: 1. The radiographic involvement of tumor to arterial circumference was not necessarily resulted in histopathological artery wall invasion; 2. the developed surgical techniques facilitated radical resection, better perioperative safety as well as oncological benefit. The feasibility of periadventitial dissection, sub-adventitial divestment and other artery-sparing techniques for ai-PC depended on the tumor invasion depth to the artery, i.e., whether the external elastic lamina (EEL) was invaded demonstrating a hallmark plane for sub-adventitial dissections. These techniques were reported to be complicated with preferable surgical outcomes comparing to arterial resection combined pancreatectomies, while the arterial resection combined pancreatectomies were considered performed in patients with more advanced disease. Conclusions: Adequate preoperative imaging modalities with which to evaluate the tumor invasion depth to the artery are to be developed. Survival benefits after these techniques remain to be proven, with more and higher-level clinical evidence needed. Key message: The current resectability evaluation criteria, which were based on radiographic circumferential involvement of the artery by tumor, was insufficient to preclude curative-intent pancreatectomies for artery-involving pancreatic cancer patients. With oncological benefit to be further proven, periarterial dissection and arterial resection have different but overlapping indications, and predicting the tumor invasion depth in major arteries was critical for surgical planning.

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Pancreatic cancer is one of the most lethal malignancies affecting people worldwide. As it is frequently diagnosed in advanced stages of the disease, the 5-year overall survival rate is <10%. Advanced stages are usually characterized by the local invasion of the superior mesenteric axis, celiac axis and portal vein and are considered a sign of unresectable cancer. The association between venous resections and survival outcomes has been widely reported. The effect of arterial invasion remains unclear as only isolated cases have been reported thus far. The present study investigated the preliminary experience in the field of arterial resection for locally advanced pancreatic cancer. Between January 2018 and January 2020 arterial resection was successfully associated with pancreatoduodenectomy in four cases. The mean age at the time of surgery was 48 years, and in all cases the indication of resection was represented by pancreatic head adenocarcinoma. Different types of venous resections were required in all cases. Postoperative reoperation was required in one case, while histopathological studies confirmed microscopic negative resection margins in all but one case. In selected cases, combined pancreatoduodenectomy with venous and arterial resection may be required to increase the chances of radical surgery.

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with poor prognosis and increased incidence. Surgical resection R0 remains the most important treatment to prolong survival in PDAC patients. In borderline and locally advanced cancer, vascular resection and reconstruction during pancreatectomy enables achieving R0 resection. This study is a comprehensive review of the literature regarding the role of venous and arterial resection with vascular reconstruction in the treatment of pancreatic cancer. The literature review is focused on the use of venous and arterial resection with immediate vascular reconstruction in pancreaticoduodenectomy. Different types of venous and arterial resections are widely described. Different methods of vascular reconstructions, from primary vessel closure, through end-to-end vascular anastomosis, to interposition grafts with use autologous veins (internal jugular vein, saphenous vein, superficial femoral vein, external or internal iliac veins, inferior mesenteric vein, and left renal vein or gonadal vein), autologous substitute grafts constructed from various parts of parietal peritoneum including falciform ligament, cryopreserved and synthetic allografts. The most attention was given to the most common venous reconstructions, such as end-to-end anastomosis and interposition graft with the use of an autologous vein. Moreover, we presented mortality and morbidity rates as well as vascular patency and survival following pancreatectomy combined with vascular resection reported in cited articles.

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BACKGROUND: The prognosis of patients with borderline resectable pancreatic cancer with arterial contact (BRPC-A) is extremely poor, and effective preoperative treatment is indispensable. We evaluated the clinical efficacy and safety of neoadjuvant chemotherapy, including gemcitabine, nab-paclitaxel and S-1 (GAS), for patients with BRPC-A. MATERIAL AND METHODS: A multicentre, single-arm, phase II study was performed. Patients were administered 1000 mg/m2 gemcitabine on day 1, 125 mg/m2 nab-paclitaxel on day 1 and 60-100 mg/day S-1 on days 1-7 during a 14-day cycle. Patients were then assessed for resectability and response to treatment after six cycles. The primary end-points were 2-year overall survival (OS) rate and median OS time (trial registration: jRCTs061180045, UMIN000016630). RESULTS: Forty-seven patients with BRPC-A were eligible for the present study. Six courses of neoadjuvant GAS regimen were completed in all eligible patients. The rate of grade III/IV toxicities occurred in 14 (30%) patients during the neoadjuvant GAS regimen. The response and disease control rates were 43% and 96%, respectively. Forty-five (96%) patients received potentially curative pancreatectomy, whereas two did not owing to disease progression. R0 resection was performed in 40 (86%) of 47 eligible patients. Eleven (24%) patients experienced postoperative major complications (>grade III), including one mortality. The 2-year OS rate and median OS time among 47 eligible patients were 70.1% and 41.0 months, respectively. CONCLUSIONS: The neoadjuvant GAS chemotherapy regimen for BRPC-A showed good efficacy with mild toxicity, resulting in a high R0 resection rate and prolonged survival in patients with BRPC-A.

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BACKGROUND: In light of recent advances in multimodality treatment, an analysis of vascular resection outcomes in surgery for hilar cholangiocarcinoma is lacking. OBJECTIVE: The aim of this meta-analysis is to summarize the currently available evidence on outcomes of patients undergoing arterial resection for the treatment of hilar cholangiocarcinoma. METHODS: A systematic literature search in the databases PubMed/MEDLINE, Cochrane Library, and CINAHL, and the trial registries ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform will be carried out. Predefined outcomes are mortality (100-day and in-hospital), morbidity (Clavien-Dindo classification, any type of complication), vascular complications (thrombosis or stenosis of the portal vein or hepatic artery, pseudoaneurysms), liver failure, postoperative bleeding, duration of surgery, reoperation rate, length of hospital stay, survival time, actuarial survival (2-, 3-, and 5-year survival), complete/incomplete resection rates, histologic arterial invasion, and lymph node positivity (number of positive lymph nodes and lymph node ratio). RESULTS: Database searches will commence in December 2020. The meta-analysis will be completed by December 2021. CONCLUSIONS: Our findings will enable us to present the current evidence on the feasibility, safety, and oncological effectiveness of surgery for hilar cholangiocarcinoma with arterial resection. Our data will support health care professionals and patients in their clinical decision-making. TRIAL REGISTRATION: PROSPERO 223396; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=223396. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31212.

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BACKGROUND AND OBJECTIVES: Although arterial involvement for advanced tumors is rare, vascular resection may be indicated to achieve complete tumor resection. Given the potential morbidity of this approach, we sought to evaluate perioperative outcomes, vascular graft patency, and survival among patients undergoing tumor excision with en bloc arterial resection and reconstruction. METHODS: From 2010 to 2020, we identified nine patients with tumors encasing or extensively abutting major arterial structures for whom en bloc arterial resection and reconstruction was performed. RESULTS: Mean age was 53 ± 20 years, and 89% were females. Diagnoses were primary sarcomas (5), recurrent gynecologic carcinomas (3), and benign retroperitoneal fibrosis (1). Tumors involved the infrarenal aorta (2), iliac arteries (6), and superficial femoral artery (1). Three patients (33%) had severe perioperative morbidity (Grade III + ) with no mortality. At a median follow-up of 23 months, eight patients (89%) had primary graft patency, and five patients (56%) had no evidence of disease. CONCLUSIONS: Arterial resection and reconstruction as part of the multimodality treatment of regionally advanced tumors is associated with acceptable short- and long-term outcomes, including excellent graft patency. In appropriately selected patients, involvement of major arterial structures should not be viewed as a contraindication to attempted curative surgery.

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OBJECTIVE: In this article, we outline the important features of pancreatic cancer surgery in cases with visceral artery encasement. BACKGROUND: Despite recent advances in diagnosis and treatment, pancreatic cancer continues to have a poor prognosis. Due to its limited response to chemotherapies, radiation, or targeted therapies, surgery (in combination with adjuvant chemotherapy) is the only potential way to treat pancreatic cancer in a curative manner. As only about 20% of the patients have surgically resectable disease at the time of diagnosis, the resection of encased visceral veins and arteries, along with neoadjuvant regimens, is one approach to treat otherwise palliative patients. METHODS: Based on a selective literature review, we discuss the results of several studies and meta-analyses, comparing the mortality and morbidity, as well as long-term survival in patients undergoing arterial resection vs standard treatment. We conducted a selective literature review in PubMed without restrictions regarding time of publication or study design. Only articles in English language were selected. CONCLUSIONS: Several studies and meta-analyses comparing resection with and without arterial resection and reconstruction showed a significantly higher post-operative mortality and morbidity and shorter long-term survival in patients who required arterial resection. In patients with tumors initially considered irresectable, the approach of neoadjuvant chemotherapy followed by resection with arterial reconstruction showed a significantly increased survival compared to palliative chemotherapy alone with acceptable postoperative morbidity. Tumor resection with arterial reconstruction following intensive preoperative chemotherapy (plus radiochemotherapy in some cases) should be considered in selected patients, as it can prolong survival and potentially lead to sustained freedom from tumor recurrence.

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While pancreatic cancer is still characterized by early systemic spread and poor outcomes, the treatment of this disease has changed significantly in recent years due to major advancements in systemic therapy and advanced surgical techniques. Broader use of effective neoadjuvant approaches combined with aggressive surgical operations within a multidisciplinary setting has improved outcomes. Borderline resectable pancreatic cancer is characterized by tumor vascular invasion, and is a setting where the combination of potent neoadjuvant chemotherapy and aggressive surgical methods, including vascular resections and reconstructions, shows its full potential. Hopefully, this will lead to improved local control and curative treatment in a number of patients with this aggressive malignancy.

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Introduction: Pancreatic cancer continues to have a poor outcome. Many patients are diagnosed with advanced disease, and in a considerable proportion, abutment or invasion of visceral arteries is present. Moreover, some patients have anatomical variations or stenosis of major visceral arteries requiring arterial reconstruction upon pancreatic cancer resection to avoid organ ischemia. Simultaneous arterial reconstruction during resection is associated with relevant morbidity and mortality. This trial evaluates the approach of visceral debranching, that is, arterial reconstruction, prior to neoadjuvant chemotherapy and tumor resection in patients with locally advanced, unresectable pancreatic cancer. Methods and Analysis: The trial includes patients with locally advanced, non-metastatic pancreatic cancer with arterial abutment or invasion (deemed primarily unresectable), variations in vascular anatomy, or stenosis of visceral arteries. The participants undergo visceral debranching, followed by current standard neoadjuvant chemotherapy (mFOLFIRINOX, gemcitabine-nab-paclitaxel, or other) and potential subsequent tumor resection. The primary outcome is feasibility, measured as the proportion of patients who start neoadjuvant therapy within 6 weeks of visceral debranching. The trial has an exact single-stage design. The proportion below which the treatment is considered ineffective is set at 0.7 (H0). The proportion above which the treatment warrants further exploration in a phase III trial is set at 0.9 (H1). With a power (1-beta) of 0.8 and a type 1 mistake (alpha) of 0.05, the required sample size is 28 patients. Feasibility of the approach will be assumed if 24 of the enrolled 28 patients proceed to neoadjuvant chemotherapy within 6 weeks from visceral debranching. Discussion: This trial evaluates a new treatment sequence, that is, visceral debranching followed by chemotherapy and resection, for pancreatic cancer with invasion or abutment of visceral arteries. The primary objective of the trial is to evaluate feasibility. Trial results will allow for estimating treatment effects and calculating the sample size of a randomized controlled trial, in which the approach will be tested if the feasibility endpoint is met. Clinical Trial Registration: clinicaltrials.gov, identifier: NCT04136769.

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Aggressive arterial resection (AR) or total pancreatectomy (TP) in surgical treatment for locally advanced pancreatic cancer (LAPC) had long been discouraged because of their high mortality rate and unsatisfactory long-term outcomes. Recently, new chemotherapy regimens such as FOLFIRINOX or Gemcitabine and nab-paclitaxel have provided more adequate patient selection and local tumor suppression, justifying aggressive local resection. In this review, we investigate the recent reports focusing on arterial resection and total pancreatectomy for LAPC and discuss the rationale of such an aggressive approach in the treatment of PC. AR for LAPCs is divided into three, according to the target vessel. The hepatic artery resection is the simplest one, and the reconstruction methods comprise end-to-end, graft or transposition, and no reconstruction. Celiac axis resection is mainly done with distal pancreatectomy, which allows collateral arterial supply to the liver via the pancreas head. Resection of the superior mesenteric artery is increasingly reported, though its rationale is still controversial. Total pancreatectomy has been re-evaluated as an effective option to balance both the local control and postoperative safety. In conclusion, more and more aggressive pancreatectomy has become justified by the principle of total neoadjuvant therapy. Further technical standardization and optimal neoadjuvant strategy are mandatory for the global dissemination of aggressive pancreatectomies.

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The efficacy of FOLFIRINOX chemotherapy gave renewed interest for surgery in case of locally advanced pancreatic ductal adenocarcinoma. Consistent series of pancreatectomy with arterial and venous resection have been reported recently and that described acceptable short and long-term outcomes in selected patients operated by high volume institutions by dedicated surgical team. In a didactical video we showed our approach for resecting a locally advanced pancreatic ductal adenocarcinoma involving both the splenomesentericoportal venous confluence and a replaced common hepatic artery arising from the superior mesenteric artery (SMA). A large dorsal pancreatic artery arising from the SMA is used for the arterial reconstruction in this particular case. The approach used entails extensive bowel mobilization, mesenteric approach to the coelio-mesenteric vessels and arterial divestment making feasible arterial and venous resection with reconstruction without graft interposition.

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BACKGROUND: Ischemic complications are still prevalent after distal pancreatectomy with en bloc celiac axis resection (DP-CAR) despite the use of preoperative arterial embolization. We described our institutional experience with arterial reconstruction during DP-CAR. METHODS: We retrospectively reviewed short- and long-term outcomes of all DP-CAR performed for pancreatic adenocarcinoma between January 1, 1995 and March 30, 2020. Outcomes were compared according to the presence of arterial reconstruction. RESULTS: Sixty consecutive DP-CARs were reviewed. Most patients underwent induction chemotherapy (85%) based on FOLFIRINOX protocol (80.3%). The hepatic artery was reconstructed in 50 patients (83.3%). The left gastric artery was reconstructed in 4 and preserved in 14 patients. A venous resection was associated during 44 DP-CARs (36 segmental venous resections/8 lateral venous resections). Ninety days mortality was 5.0% with 48.3% (n = 29) overall rate of morbidity. Postoperative outcomes in term of mortality, morbidity, and ischemic events between patients with and without arterial reconstruction were similar despite a higher rate of venous resection (81% vs. 40%; p = 0.005) and more complex cases (Mayo clinic DP-CARs class 1B, 2A, and 3A) in the reconstructed group. CONCLUSION: Arterial reconstruction represents a safe surgical option during DP-CAR to lessen postoperative ischemic events. This technique, reserved to high volume centers expert in vascular resection during pancreatectomy, deserves further comparison with standard technique in a larger setting.

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PURPOSE: To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated. METHODS: In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery. RESULTS: From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p < 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p < 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (< 1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively. CONCLUSIONS: The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.

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