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Meta‐analysis of benefits of portal–superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma. BJS 2016; 103: 179-191.

Published: 10th December 2015

Authors: F. Giovinazzo, G. Turri, M. H. Katz, N. Heaton, I. Ahmed

Background

Pancreatic ductal adenocarcinoma has a poor prognosis without surgery. No standard treatment has yet been accepted for patients with portal–superior mesenteric vein (PV‐SMV) infiltration. The present meta‐analysis aimed to compare the results of pancreatic resection with PV‐SMV resection for suspected infiltration with the results of surgery without PV‐SMV resection.

Method

A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines from the time of inception to 2013. The inclusion criteria were comparative studies including patients who underwent pancreatic resection with or without PV‐SMV resection. One, 3‐ and 5‐year survival were the primary outcomes.

Results

Twenty‐seven studies were identified involving a total of 9005 patients (1587 in PV‐SMV resection group). Patients undergoing PV‐SMV resection had an increased risk of postoperative mortality (risk difference (RD) 0·01, 95 per cent c.i. 0·00 to 0·03; P = 0·02) and of R1/R2 resection (RD 0·09, 0·06 to 0·13; P < 0·001) compared with those undergoing standard surgery. One‐, 3‐ and 5‐year survival were worse in the PV‐SMV resection group: hazard ratio 1·23 (95 per cent c.i. 1·07 to 1·43; P = 0·005), 1·48 (1·14 to 1·91; P = 0·004) and 3·18 (1·95 to 5·19; P < 0·001) respectively. Median overall survival was 14·3 months for patients undergoing pancreatic resection with PV‐SMV resection and 19·5 months for those without vein resection (P = 0·063). Neoadjuvant therapies recently showed promising results.

Conclusion

This meta‐analysis showed increased postoperative mortality, higher rates of non‐radical surgery and worse survival after pancreatic resection with PV‐SMV resection. This may be related to more advanced disease in this group.

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2 Comments

BJS Admin

3 years ago

We read with interest the meta-analysis (1996-2013) by Giovinazzo et al. Despite venous resection (VR) being accepted as a means to achieve complete tumour clearance for pancreatic adenocarcinoma with venous involvement, this meta-analysis demonstrated increased postoperative mortality, more frequent non-radical surgery and lower survival after pancreatectomy with VR. The authors identified some studies encouraging neoadjuvant treatment in ‘borderline’ resectable cancer. In 2015, we reported a French survey comparing 997 standard pancreaticoduodenectomies (PD) and 402 (29%) PD with VR. Long-term survival was significantly altered after upfront VR, even in N0R0 patients; particularly, in VR patients, neoadjuvant treatment was associated with an increased rate of R0 resection (p=0.05), a lower rate of nodal involvement (p=0.0001), and a better survival (p=0.031) (1). Other studies have confirmed high histopathologic response rate (2) and median survivals equal to those observed in resectable disease (3) with neoadjuvant treatment. Our results (1) and the meta-analysis by Giovinazzo et al. suggest that vascular infiltration indicates more aggressive tumour biology. The portal vein channel is probably a crucial way of lymphatic tumour spread (4), and the vascular margin is a major R1 site. Thus, VR should be performed after a selection process including neoadjuvant treatment. This strategy might be better than up-front pancreatectomy with VR in patients with any suspected venous involvement on imaging (5), who should be classified as borderline resectable. The anticipated better outcome may outweigh the risk of over treating patients with only inflammatory adhesions to venous wall.

Jean Robert Delpero
Antonio Sa Cunha
Alain Sauvanet
François Paye
Ph. Bachellier
on behalf of the French Association of Surgery

Departments of Surgery
Institut Paoli Calmettes
232 Boulevard de Sainte-Marguerite
Marseille 13009
France
jrdelpero@numericable.fr

References:
1. Delpero JR, Boher JM, Sauvanet A, Le Treut YP, Sa-Cunha A, Mabrut JY et al. Pancreatic adenocarcinoma with venous involvement: is up-front synchronous portal-superior mesenteric vein resection still justified? A survey of the Association Française de Chirurgie. Ann Surg Oncol 2015; 22: 1874-1883.
2. Pietrasz D, Marthey L, Wagner M, Blanc JF, Laurent C, Turrini O et al. Pathologic Major Response After FOLFIRINOX is Prognostic for Patients Secondary Resected for Borderline or Locally Advanced Pancreatic Adenocarcinoma: An AGEO-FRENCH, Prospective, Multicentric Cohort. Ann Surg Oncol 2015; 22 Suppl 3: 1196-1205.
3. Sadot E, Doussot A, O’Reilly EM, Lowery MA, Goodman KA, Do RK et al. FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma. Ann Surg Oncol 2015, 22: 3512-3521.
4. Hirono S, Tani M, Kawai M, Okada K, Miyazawa M, Shimizu A et al. Identification of the lymphatic drainage pathways from the pancreatic head guided by indocyanine green fluorescence imaging during pancreaticoduodenectomy. Dig Surg 2012, 29: 132-139.
5. Evans DB, Ritch PS, Erickson BA. Neoadjuvant therapy for localized pancreatic cancer: support is growing? Ann Surg 2015; 261: 18-20.

    BJS Admin

    3 years ago

    Dear Professor Delpero

    Thank you very much for your letter and the comments about our published meta-analysis. This meta-analysis and your paper support worse long-term survival after upfront vein resection (VR) and possible better outcomes after neoadjuvant therapies in patients affected by pancreatic cancer (PaCa) with Portal Vein-Superior Mesenteric Vein (PV-SMV) involvement (1,2).

    Neoadjuvant therapies have been investigated in several non-randomized trials showing a resection rate in more than a third of the patients with an increased rate of R0 resections and downstaged diseases (3). However, evidence from RCTs is still missing. Therefore, those data have to be interpreted with caution because the low level of evidence.

    The multicentre prospective, randomized, ongoing trial ESPAC-5F is investigating the role of neoadjuvant chemotherapy and radiotherapy along with surgery in borderline resectable PaCa. The results of the trial may clarify about the effectiveness of different neo- adjuvant treatment options and the role of the upfront VR (4).

    These results will be a better guidance to clinicians if these cases represent more aggressive tumor and response to neoadjuvant therapy may be a way of selecting cases suitable for surgery. Recently, Catenacci et al. showed that in a pilot study that Circulating Tumor Cells (CTCs) may be detected in portal vein blood of patients affected by PaCa independently from the disease stage. Those results might be an additional way forward in detecting systematic disease before VR (5).

    From a surgical point of view the depth and the longitudinal extension of the PV-SMV invasion might impact on the R0 and the survival rate, and to the best of our knowledge those factors have never been extensively investigated. Therefore, central questions that need to be addressed in future will be the type of neoadjuvant treatments and the extent of vascular resections.

    Francesco Giovinazzo
    Nigel Heaton
    Irfan Ahmed

    Department of Surgery
    Aberdeen Royal Infirmary
    Foresterhill Road
    Aberdeen AB25 2ZN
    UK
    francesco.giovinazzo@nhs.net

    References:
    1. Giovinazzo, F et al. Meta-analysis of benefits of portal-superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma. Br J Surg 2016; 103: 179-191.
    2. Delpero, JR et al. Pancreatic adenocarcinoma with venous involvement: is up-front synchronous portal-superior mesenteric vein resection still justified? A survey of the Association Francaise de Chirurgie. Ann Surg Oncol 2015; 22: 1874-1883.
    3. Tsai, S. Evans, DB. Therapeutic Advances in Localized Pancreatic Cancer. JAMA Surg 2016.
    4. ESPAC-5F. http://www.isrctn.com/ISRCTN89500674, 2014.
    5. Catenacci, DV et al. Acquisition of Portal Venous Circulating Tumor Cells From Patients With Pancreaticobiliary Cancers by Endoscopic Ultrasound. Gastroenterology 2015; 149: 1794-1803 e4.