Introduction

The DIPLOMA-trial showed comparable R0 resection rates after minimally invasive left pancreatectomy (MILP) and open left pancreatectomy (OLP) in patients with upfront resectable pancreatic cancer. Data on long-term overall and disease-free survival (OS, DFS) are currently lacking but are required before the oncological efficacy of MILP can be confirmed.

Aims & Methods

The international randomized non-inferiority DIPLOMA trial included patients with upfront resectable pancreatic cancer from 35 centers in 12 countries. Participants were randomly assigned to undergo MILP (laparoscopic and robotic) or OLP. Patients were blinded for the surgical approach. The primary endpoint of the trial was radical resection (R0) rate in patients who ultimately underwent resection. The current study describes OS and DFS after a minimum follow-up of 36 months.

Results

Between May 2018 and May 2021, 258 patients were randomized to MILP (131 patients) and OLP (127 patients). After a median follow-up of 38 months (IQR 36–46 months), 134 patients (52%) had died and 127 patients (55%) experienced disease recurrence. OS did not differ significantly between the MILP and OLP groups (median 32 vs 34 months; stratified hazard ratio [95% CI], 1.02 [0.72–1.44]; p=0.92). Also, DFS did not significantly differ between MILP and OLP (median, 21 vs 17 months; stratified hazard ratio [95% CI], 0.96 [0.68–1.35]; p=0.81). Adjuvant therapy was administered in 79 patients after MILP (79/113 [70%]) and 79 patients after OLP (79/110 [72%], p=0.63). Time to adjuvant therapy was comparable between groups (median 59 vs 56 days; p=0.92).

Conclusion

In the long-term follow-up of the DIPLOMA trial, OS and DFS did not differ significantly between MILP and OLP confirming the oncological safety of MILP in patients with upfront resectable pancreatic cancer.

Disclosure

Marc G. Besselink and Mohammad Abu Hilal have been awarded with a grant from Medtronic for the DIPLOMA-trial. Medtronic had no role in the design and conduct of the study; trial design, patient recruitment, data collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The study group has not been paid to write this article by any agency.

Introduction

As curative criteria of undifferentiated-type gastric cancer (UD-GC) by endoscopic submucosal dissection (ESD), it is defined lesions fulfill the pathological size ≤ 20 mm, pT1a, absence of ulcerative findings (UL-0), absence of lympho-vascular invasion (LVI-0) and R0 resection in Japanese gastric cancer treatment guidelines. However, additional gastrectomy is needed for other UD-GCs. Meanwhile, it is reported that pathological size of ≤ 40 mm, pT1a, purely UD-GC (without differentiated-type [D-type] components) patients with UL-0 and LVI-0 did not show lymph node metastasis (LNM). Additionally, it is reported that no LNM occurred in the patients with pathological size > 20 mm, pT1a, UD-GC, UL0, LVI-0, and retained double-layer structure (as distribution of cancers in mucosa, the upper layer primarily comprises intracytoplasmic abundant mucin with an eccentric nucleus, and the lower layer primarily comprises poor intracytoplasmic mucin and acidophilic cytoplasm). However, all of these studies were single-center retrospective studies with a small sample size of surgical cases, and there have been no multi-institutional studies with central pathological review (CPR).

Aims & Methods

This was a multicenter retrospective study from 45 Japanese institutions to determine the proportion of LNM, and clarify the clinicopathological characteristics of the lesions without LNM (as no metastasis of lymph nodes in surgical specimens). We included patients pathologically diagnosed with purely UD-GC, lesion size 21-40 mm, pT1a, UL0, LVI-0 by initial gastrectomy or gastrectomy after ESD at each institution. Patient information was entered into an electronic case report form via electronic data capture. In addition, seven unstained slides, including the deepest invasive area of each lesion, were collected from each institution, and hematoxylin-eosin staining and immunostaining for MUC5AC and MUC6 were performed. As a CPR, two pathologists assessed whether UL-0, pT1a, and absence of minor tubular components (as a small amount of tubular components) were observed. UL-1, pT1b, D-type dominance or unevaluable specimens were excluded. Further, whether the lesion involved the entire mucosal layer and whether a double-layer structure was present. The final decision on the lesions with discrepancies was made through discussion with another member of the CPR via web meeting.

Results

Of the 652 patients enrolled, 127 were excluded due to UL-1, pT1b, D-type dominance or unevaluable specimens by the CPR. In 525 eligible patients (initial gastrectomy; 444, gastrectomy after ESD; 81), 10 patients had LNM (1.8%, 95% Confidence Interval [CI] 0.9-3.5%). Comparing 10 patients in the LNM group with 515 patients in the non-LNM group, there were no significant differences in the pre-treatment endoscopic findings. Meanwhile, the results of the CPR revealed that the absence of minor tubular components is more frequent in the non-LNM group than that in the LNM group (365/515, 70.9% vs 3/10, 30%, p=0.011). When stratified by the results of the CPR, patients with preserved double-layer structure did not have LNM (0/41, 95%CI 0-8.6%). Meanwhile, patients without minor tubular components had 0.8% as proportion of LNM, and upper of 95%CI was low among each population (3/365, 95%CI 0.2-2.4%).

Conclusion

There were 1.8% of LNM in all eligible patients. In contrast, as purely UD-GC, lesion size 21-40 mm, pT1a, UL0, LVI-0 without minor tubular components had a low proportion of LNM, they are promising candidates for the expansion as the curative criteria of ESD.