The value of splenectomy during left-sided pancreatectomy for pancreatic ductal adenocarcinoma: predefined subanalysis in the DIPLOMA randomized trial

Dear Editor, Splenectomy is the current standard during left-sided pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) with the goal to perform adequate lymphadenectomy in the splenic hilum. The added value of splenectomy regarding resection of involved lymph nodes (LNs) and survival benefit has not been confirmed. Moreover, asplenia holds severe risks, including the high mortality risk of overwhelming post-splenectomy sepsis (50–70%)1. Several studies have reported conflicting results on the value of splenectomy during left-sided pancreatectomy for PDAC. Some reported few or no tumour-positive splenic hilum LNs2, whereas others identified metastasis in up to 5.2% of patients, supporting concomitant splenectomy3,4. However, these studies were small, retrospective, single-centre series lacking standardized, prospective pathology assessment and clear definitions of the splenic hilum2–4. Therefore, the benefit of splenectomy remains uncertain without prospective studies. The international, multicentre, randomized DIPLOMA-trial included 258 patients with resectable left-sided PDAC (2018–2021) and included a prespecified assessment of splenic hilum LNs5. For this subanalysis, patients with proven PDAC and complete postoperative histopathology assessment were included. Standardized surgical and histopathological procedures were used; all pathologists were specifically asked to examine splenic hilum LNs (station 10). The preoperative CT images from all patients with splenic LN metastasis (splenic LN+) were re-examined by an independent radiologist. In this subanalysis, 185 patients after left-sided pancreatectomy for PDAC were included. The rate of splenic LN+ was 2.2% (4/185 patients). Overall median LN yield was 23.0 (i.q.r. 15.0–32.0) and in the splenic hilum 3.0 (i.q.r. 1.0–6.0). There was no LN yield in the splenic hilum in 32 patients (32/167, 19.2%). In total, four patients had splenic LN+ (4/185, 2.2%), three with pancreatic tail PDAC (3/67, 4.5%) and one with pancreatic body PDAC (1/118, 0.8%). No further statistical analyses have been performed due to the low number of patients with splenic LN+. There were no clear trends in preoperative characteristics when comparing patients who had splenic LN+ (Table 1). Three of four patients also had LN metastases both superior and inferior of the pancreas. One patient had LN metastasis solely in the splenic hilum. Only for this patient has the number of splenic LN+ had an impact on the N-stage, and therefore on prognosis. However, the total LN yield in that patient was 12, and no LNs were yielded inferior of the pancreas. Four patients with splenic hilum lymph node involvement after left-sided pancreatectomy for primary resectable pancreatic cancer CA19-9, carbohydrate antigen 19-9; CEA, carcinoembryonic antigen. Four patients with splenic hilum lymph node involvement after left-sided pancreatectomy for primary resectable pancreatic cancer CA19-9, carbohydrate antigen 19-9; CEA, carcinoembryonic antigen. This predefined subanalysis of the multicentre, randomized DIPLOMA trial is the first prospective study on splenic hilum LN metastasis in patients with resectable PDAC. Splenic LN+ were found in only 4 of 185 (2.2%) included patients. Three of these patients had pancreatic tail cancer, resulting in a 0.8% rate (1/118 patients) for those with pancreatic body cancer. The low (2.2%) incidence of splenic LN+ aligns with most previous (retrospective) studies, which reported rates of 0–5%2–4. These findings prompt an important debate on the need for splenectomy as standard-of-care during the resection of left-sided pancreatic cancer, especially in patients with pancreatic body PDAC. However, some limitations should be considered when interpreting the results. First, the small number of patients with splenic LN+ limits the ability to draw firm conclusions about the significance of these metastases and their impact on survival. Second, this study, like previous ones, only examined LNs in the splenic hilum, rather than the entire peri-splenic hilum. A local radical spleen-preserving procedure wherein PDAC could be resected would involve the Warshaw procedure including resection of the splenic vessels and the perirenal fascia of Gerota6,7. Herein, the surgeon would typically fire staplers immediately behind the tip of the pancreatic tail, leaving the left gastroepiploic artery and all peripancreatic fat in situ, which could potentially contain more LN+. The data demonstrate that splenic hilum LN+ is rare (<3%) in patients after left-sided pancreatectomy for PDAC in the pancreatic tail and especially the pancreatic body. Further prospective studies on the role of splenectomy during left pancreatectomy for pancreatic cancer are needed. Matteo de Pastena and Roberto Salvia (Department of General and Pancreatic Surgery—Pancreas Institute, University Hospital of Verona, Verona, Italy), Tore Tholfsen (Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway), Gianpaolo Balzano (Department of Surgery, San Raffaele Hospital IRCCS, Università Vita-Salute, Milan, Italy), Zahir Soonawalla (Oxford University Hospital NHS Foundation Trust, Oxford, UK), Misha Luyer (Department of Surgery, Catharina Ziekenhuis, Eindhoven, The Netherlands), David Kooby (Emory University Hospital, Atlanta, USA), Svein Olav Bratlie (Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden), Tobias Keck (Department of Surgery, UKSH campus Lübeck, Lübeck, Germany), Daan Lips (Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands), Ugo Boggi (Department of Surgery, Universitá di Pisa, Pisa, Italy), Safi Dokmak (Beaujon Hospital, Clichy, France), Bas Groot Koerkamp (Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands), Giovanni Ferrari (Niguarda Ca’Granda Hospital, Milan, Italy), Olivier Saint Marc (Centre Hospitalier Regional Universitaire Orleans, Orleans, France), Andrea Pietrabissa (IRCCS Policlinico San Matteo Pavia, Pavia, Italy), Adnan Alseidi (Virginia Mason Medical Center, Seattle, USA), I. Quintus Molenaar (University Medical Center Utrecht, Utrecht, The Netherlands), Ruben de Kleine (Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands), Thilo Hackert (Heidelberg University Hospital, Heidelberg, Germany), Ales Tomazic (University Medical Center Ljubljana, Ljubljana, Slovenia), Patricia Sanchez Velazquez (Hospital del Mar, Barcelona, Spain), Jean Michel Fabre (Hôpital Saint Eloi, Montpellier, France), Igor Khatkov (Moscow Clinical Scientific Center, Moscow, Russian Federation) and Antonio Sa Cunha (Paul-Brousse Hospital, Villejuif, France) Mohammad Abu Hilal and Marc G. Besselink received grants from Medtronic Covidien AG, Ethicon, Johnson & Johnson Medical Limited, and the Dutch Gastroenterology Society for the DIPLOMA trial, and Intuitive Surgical grants for the E-MIPS registry, the DIPLOMA-2 trial, the DIPLOMA-2 × 2 trial, and Dutch and European training programmes in robotic pancreatoduodenectomy. M.G.B and M.A.H shared senior authorship. The authors declare no conflict of interest. The authors attest that the data supporting the findings of this study are included with the article and its Supplementary. Raw data are available and can be obtained from the corresponding author upon reasonable request. Caro Bruna (Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Writing—original draft), Jony van Hilst (Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Writing—review & editing), Alessandro Esposito (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Dyre Kleive (Conceptualization, Data curation, Investigation, Resources, Supervision, Writing—review & editing), Massimo Falconi (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), John Primrose (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Maarten Korrel (Conceptualization, Data curation, Funding acquisition, Investigation, Project administration, Validation, Writing—original draft), Denise Bianchi (Conceptualization, Supervision, Validation, Writing—review & editing), Alessando Zerbi (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Arto Kokkola (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Giovanni Butturini (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Bergthor Björnsson (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Mario Morone (Data curation, Investigation, Resources, Writing—review & editing), Riccardo Casadei (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Ravi Marudanayagam (Conceptualization, Data curation, Resources, Supervision, Writing—review & editing), Marc Besselink (Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing—review & editing), and Mohammed Abu Hilal (Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing—original draft, Writing—review & editing)

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