Professor Alessandro Zerbi of the Humanitas Research Hospital Para-aortic Lymphnodes Removal During Upfront Pancreaticoduodenectomy (PALN).
Summary Brief:
The only curative alternative for patients affected by pancreatic ductal adenocarcinoma (PDAC) is pancreaticoduodenectomy (PD) combined with lymphadenectomy. In 2014, “normal lymphadenectomy” was established by the International Study Group on Pancreatic Surgery (ISGPS), which is mandatory for PDAC during PD. Lymphadenectomy may include the elimination of the nodes of the hepatoduodenal ligament (stations 5, 6, 12b1, 12b2, 12c, Japanese Pancreas Society classification), the nodes of the hepatic artery (station 8a), the posterior surface of the pancreatic head (stations 13a and 13b), the upper mesenteric artery (stations 14a on the right side, 14b on the right side) and the nodes of the anterior surface (stations 13a and 13b) There is still controversy regarding the inclusion of para-aortic lymph nodes (PALN) (station 16) in the regular lymphadenectomy. In addition, several retrospective or prospective studies have indicated that there is a major negative prognostic effect on the existence of PALN metastases. Until now, no randomized trials have been reported comparing PD associated with standard lymphadenectomy with or without PALN elimination. The purpose of this study is to determine whether the removal of station 16 during PD for PDAC can routinely be included in the standard lymphadenectomy.
Description in detail:
The latest therapy for pancreatic ductal adenocarcinoma (PDAC) is pancreaticoduodenectomy (PD) with lymphadenectomy. During the last two decades, the ideal lymphadenectomy during PD (standard versus extended) has been largely debated. Four subsequently published randomized controlled trials ( RCTs) reported no survival advantage and no claims could be made to support the role of extended lymphadenectomy during PD based on the evidence of these studies. Two meta-analyses, the first from Michalski et al., in which 3 RCTs were studied, and the second from Iqbal et al., in which both RCTs and cohort studies were included, both of which showed no benefit from extended lymphadenectomy, also underscored a similar conclusion. The concept of lymphadenectomy, however, differed significantly between the RCTs. The International Study Group on Pancreatic Surgery (ISGPS) identified ‘normal lymphadenectomy’ during PD for PDAC for this purpose in 2014. Lymphadenectomy could include the cutting of the nodes of the hepatoduodenal ligament (stations 5, 6, 12b1, 12b2, 12c, Japanese Pancreas Society classification), the nodes of the hepatic artery (station 8a), the posterior surface of the pancreatic head (stations 13a and 13b), the superior mesenteric artery (stations 14a on the right side, 14b on the left side) and the nodes of the anterior surface of the pancreatic head (stations 13a and 13b). As ‘extra-regional’ lymph nodes, para-aortic lymph nodes (PALN; station 16) are considered. Some questions about PALN are still open: a) should station 16 removal be routinely included in the normal lymphadenectomy for PDAC during PD? (b) can PD be avoided in the event of station 16 removal and intraoperative demonstration of PALN metastases in the frozen section? Several retrospective studies have indicated that, relative to patients with negative PALN, the prognosis of patients with metastatic PALN is substantially worse. On this topic, two recent meta-analyses have been released, confirming that PALN metastases are associated with poor prognosis in PDAC patients. However, these meta-analyses concluded that the conclusive avoidance of PD in these cases needs further study due to the existence of certain long-term survivors, even in cases of PALN metastasis. No consensus has been reached so far in the case of intraoperative metastatic PALN. In addition, it is still not clear if PALN removal should be regularly performed during PD. Until now, no randomized studies have been reported comparing PD with or without PALN elimination. There was detailed debate on the removal of PALN in 2014 during the consensus meeting of the ISGPS: no clear recommendation on routinely dissecting station 16 was developed and it was not included in regular lymphadenectomy. For this purpose, in order to determine whether their removal could routinely be included in standard lymphadenectomy during PD for PDAC, we decided to plan this multicentric RCT that compares upfront PD with and without the removal of PALN.