Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer (original) (raw)

Extended Lymphadenectomy in Patients With Pancreatic Cancer Is Debatable

World Journal of Surgery, 2013

Lymph node staging is one of the most important factors in determining the prognosis after resection of pancreatic ductal adenocarcinoma. Despite ongoing efforts to further refine lymph node staging, the debate on the extent of lymphadenectomy during pancreaticoduodenectomy is still open. The purpose of this review was to summarize the evidence about performing standard lymphadenectomy during curative resection of pancreatic cancer. All four prospective randomized controlled trials published concluded that extended lymphadenectomy does not contribute to better oncologic outcome for patients with adenocarcinoma of the pancreatic head. Indeed, one major drawback of extended lymphadenectomy is the higher risk of persistent postoperative diarrhea. No prospective randomized studies could be found on the role of extended lymphadenectomy in patients with adenocarcinoma of the corpus and tail. Based on current evidence there is no indication that extended lymphadenectomy should be performed routinely during resection of pancreatic cancer. Emmanuel Melloul contributed equally as first author. Michelle L. DeOliveira and Pierre-Alain Clavien contributed equally as senior author.

Extent of lymphadenectomy in the resection of pancreatic cancer. Analysis of the existing evidence

2005

Pancreaticoduodenectomy is considered the standard procedure for the surgical treatment of the pancreatic head cancer. However, the extent of lymph node clearance associated to the procedure is still largely debated. Arguments in favour of an extended lymphadenectomy are the regular progression of lymph node invasion, without skip metastases, and the removal of the extrapancreatic neural plexus that is invaded in 52-72% of patients. Arguments against the extended lymphadenectomy are the failure of extended lymphadenectomy to improve survival in other cancers, and the severe diarrhoea that follows the skeletonisation of the superior mesenteric artery. After Ishikawa's paper, several retrospective studies supported a longer survival after an extended than after a standard lymphadenectomy, but as much retrospective studies failed to demonstrate any difference. Only three prospective randomised controlled trials have been performed so far. Unfortunately all are underpowered, and the substantial differences in the surgical procedures, in the adjuvant treatment, and in the length of follow-up make the comparison impossible. Only one study reports a significantly longer survival for lymph node positive patients who underwent an extended lymphadenectomy, but adjuvant treatment was not performed. Furthermore, the difference was of minimal clinical impact. At least two adequately powered prospective Randomised Controlled Trials including a true extended lymphadenectomy, and a standardised adjuvant treatment, would be required to answer the question. Unfortunately, we have not yet a standardised adjuvant (or neoadjuvant) treatment, and we do not know the impact of such treatment on the expected statistical difference in the survival after a standard or extended lymphadenectomy. The lot of work required to perform such trials probably doesn't worth the expected results.

Extended pancreatic resections and lymphadenectomy: An appraisal of the current evidence

World Journal of Gastrointestinal Surgery, 2010

Surgery remains the mainstay of treatment for pancreatic ductal adenocarcinoma and complete removal of the cancer confers a definite survival advantage, especially in early disease. However, the majority of patients do not present with early disease, thus precluding the chance of a cure by standard pancreatoduodenectomy (PD), distal pancreatectomy or total pancreatectomy. For this reason, pancreatic surgeons have attempted to push the limits of resection over the last three decades. The aim of these resections has been to determine whether obtaining a complete resection by extending the limits of conventional resection in patients with advanced disease will yield the results seen with PD alone in early disease. This article revisits the data from such studies in an attempt to determine if the available literature supports the performance of extended resections for pancreatic cancer in terms of improvement of survival.

Extended Versus Standard Lymphadenectomy for Pancreatic Head Cancer: Meta-Analysis of Randomized Controlled Trials

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2015

The evidence for improved prognostic assessment and long-term survival for extended pancreatoduodenectomy (EPD) compared to standard pancreatoduodenectomy (SPD) in patients with carcinoma of the head of the pancreas has not been considered from only randomized controlled trials (RCTs). The aim of this study was to conduct a systematic review and meta-analysis of the outcomes comparing SPD and EPD in RCTs. Searches were performed on MEDLINE, Embase and Cochrane databases using MeSH keyword combinations: 'pancreatic…

Value of regional lymphadenectomy in pancreatic cancer

HPB: Official Journal of The International Hepato Pancreato Biliary Association, 2005

Radical surgical resection and adjuvant chemotherapy are the goal standard to attempt significant long term survival in patients suffering from ductal pancreatic cancer. The role of extended lymph-node dissection is still a debated issue. In this paper a deep review of the experiences reported in the literature is carried out. Several studies are limited, not randomized and retrospective: generally speaking they seem to suggest a positive role in node dissection. Unfortunately, this trend is not confirmed in the only two trials conducted in a prospective and randomized setting. Moreover the results of these studies are also difficult to compare. At the moment we can say that extended lymphadenectomy does not play a determinant role for long term survival but a positive trend has been shown for node positive patients.

The Role of Extended Lymphadenectomy for Adenocarcinoma of the Head of the Pancreas: Strength of the Evidence

Journal of Gastrointestinal Surgery, 2008

With improvements in the safety of Whipple resection in recent decades, surgeons have continued to explore the role of more extensive lymphadenectomy in hope of improving long-term survival. A systematic literature search of level I evidence addressing the role of the extent of lymphadenectomy was undertaken. Only reports of prospective, randomized controlled trials comparing pancreaticoduodenectomy with standard lymphadenectomy to pancreaticoduodenectomy with extended lymphadenectomy where information regarding survival, morbidity, mortality, the number of resected lymph nodes in each group and detailed operative technique were included. Four prospective, randomized trials comprising some 424 patients and one meta-analysis were identified. In aggregate, these studies confirmed that the number of resected lymph nodes was significantly higher in the pancreaticoduodenectomy with extended lymphadenectomy group. Morbidity and mortality rates were comparable. Postoperative diarrhea in the early months after operation was problematic in patients undergoing extended lymphadenectomy. In none of the studies was a benefit in long-term survival demonstrated. Standard pancreaticoduodenectomy continues to be the operation of choice for adenocarcinoma of the head of the pancreas.

The role of extended resection in pancreatic adenocarcinoma: Is there good evidence-based justification?

Pancreatology, 2004

Thus far, there are no studies concerning the radicality of pancreaticoduodenectomy which, in well-performed, randomized-controlled trials employing high standards of evidence-based medicine, show a benefit over extended lymphadenectomy. The results of the only two prospective randomized studies are not comparable and both are underpowered (level of evidence Ib). Therefore, it is still unclear whether extended lymphadenectomy for pancreatic carcinoma improves outcome. Only one study suggests a positive tendency toward increased survival rates in node-positive patients. Extended approaches including additional venous resection can be performed without a rise in the morbidity and mortality rates of patients with pancreatic carcinoma. In the future appropriately powered randomized trials of standard vs. extended resections may show the benefit of extended surgical resections. In addition, well powered trials of postoperative adjuvant therapies or preoperative neoadjuvant strategies together with surgical resections may identify more effective combinations showing a survival benefit in patients with pancreatic carcinoma.

Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS)

Surgery, 2014

The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognos...

A comparison of pancreaticoduodenectomy with extended pancreaticoduodenectomy: A meta-analysis of 1909 patients

European Journal of Surgical Oncology (EJSO), 2009

Aim: To compare outcomes between pancreaticoduodenectomy (PD) and extended pancreaticoduodenectomy (EPD) from all published comparative studies in the literature. Methods: Using meta-analytical techniques the present study compared operative details, post-operative adverse events and survival following PD and EPD. Comparative studies published between 1988 and 2005 of PD versus EPD were included. End points were classified into peri-operative details, post-operative complications including 30 day mortality, and survival as measured during follow up. A random effect model was employed. Results: Sixteen comparative studies comprising 1909 patients (865 PD and 1044 EPD), including 3 randomized controlled trials with 454 patients (226 PD and 228 EPD) were identified. Tumour size was comparable between the groups (weighted mean difference (WMD) À0.16 cm, p ¼ 0.76). Significantly more lymph nodes were harvested from those patients undergoing EPD (WMD p ¼ 14 nodes, p 0.001). Operative time was longer in EPD (WMD À48.9 min, p < 0.001) and there was a trend towards fewer positive resection margins (odds ratio (OR) 1.78, p ¼ 0.080). Peri-operative adverse events were similar between the groups with only delayed gastric emptying (OR 0.59, p ¼ 0.030) occurring less frequently in the PD group. Peri-operative mortality (OR 1.48, p ¼ 0.180) and long-term survival (hazard ratio 0.77, p ¼ 0.100) showed a non-significant trend favouring EPD. Conclusions: EPD is associated with a greater nodal harvest and fewer positive resection margins than PD. However, the risk of delayed gastric emptying is increased and no significant survival benefit has been shown. Better designed, adequately powered studies are required to settle this question.