Impact of Resection Margin Status in Patients with Pancreatic Cancer: a National Cohort Study

Kaltenmeier, Christof; Nassour, Ibrahim; Hoehn, Richard S.; Khan, Sidrah; Althans, Alison R.; Geller, David A.; Paniccia, Alessandro; Zureikat, Amer H.; Tohme, Samer

doi:10.1007/s11605-020-04870-6

Cited by 21 publications

(15 citation statements)

References 26 publications

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“…Nevertheless, the rates of tumor recurrence remain high, limiting the quality of life and long-term survival of patients with PDAC (4). Several factors have been associated with diminished overall survival (OS) in pancreatic cancer including tumor stage, lymph node metastases and involvement of the resection margins (7,8). However, the aforementioned features are simply indicative of a highly aggressive tumor biology and do not shed mechanistic insight on disease progression.…”

Section: Introductionmentioning

confidence: 99%

Distinct Stromal and Immune Features Collectively Contribute to Long-Term Survival in Pancreatic Cancer

et al. 2021

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Background: The aggressive biology and treatment refractory nature of pancreatic ductal adenocarcinoma (PDAC) significantly limits long-term survival. Examining the tumor microenvironment (TME) of long-term survivors (LTS) of PDAC offers the potential of unveiling novel biological insights and therapeutic targets.Methods: We performed an integrated approach involving immunophenotyping, stromal scoring and histomorphological profiling of a cohort of 112 PDAC-cases, including 25 long-term survivors (LTSs, OS ≥ 60 months). Mutational frequencies were assessed using targeted next generation sequencing. Finally, we validated our findings in silico using an external cohort of microarray data from PDAC patients.Results: LTS cases exhibit a largely quiescent population of cancer-associated fibroblasts (CAFs). Immune profiling revealed key differences between LTS and NON-LTS cases in the intratumoral and stromal compartments. In both compartments, LTS cases exhibit a T cell inflamed profile with higher density of CD3+ T cells, CD4+ T cells, iNOS+ leukocytes and strikingly diminished numbers of CD68+ total macrophages, CD163+ (M2) macrophages and FOXP3+ Tregs. A large proportion of LTS cases exhibited tertiary lymphoid tissue (TLT) formation, which has been observed to be a positive prognostic marker in a number of tumor types. Using a Random-Forest variable selection approach, we identified the density of stromal iNOS+ cells and CD68+ cells as strong positive and negative prognostic variables, respectively. In an external cohort, computational cell-type deconvolution revealed a higher abundance of T cells, B lymphocytes and dendritic cells (DCs) in patients with long-term OS compared to short-term survivors. Thus, in silico profiling of long-term survivors in an external cohort, strongly corroborated the T cell-inflamed TME observed in our LTS group.Conclusions: Collectively, our findings highlight the prognostic importance of TME profiles in PDAC, underlining the crucial role of tumor associated macrophages (TAMs) and the potential interdependence between immunosuppressive TAMs and activated CAFs in pancreatic cancer. Additionally, our data has potential for precision medicine and patient stratification. Patients with a T cell inflamed TME might derive benefit from agonistic T cell antibodies (e.g., OX40 or CD137 agonists). Alternately, patients with activated CAFs and high infiltration of immunosuppressive TAMs are highly likely to exhibit therapeutic responses to macrophage targeted drugs (e.g., anti-CSF1R) and anti-CAF agents.

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Section: Introductionmentioning

confidence: 99%

Distinct Stromal and Immune Features Collectively Contribute to Long-Term Survival in Pancreatic Cancer

et al. 2021

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“…A national cohort study also showed that positive margin predicts a poorer survival than R0 resection in patients treated with pancreatectomy for PDAC. 23 In contrast, a few studies showed that the resection margin itself is not an independent risk factor for OS. 24 More research is needed, but reviewing the studies published so far, including the current study, it seems possible to conclude that resection margin is a risk factor for survival outcome.…”

Section: Discussionmentioning

confidence: 97%

Effect of resection margin status on recurrence pattern and survival in distal pancreatectomy for left‐sided pancreatic ductal adenocarcinoma

Kwon

Lee

Park

et al. 2022

J Hepato Biliary Pancreat

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Background The association of resection margin status with recurrence and survival after pancreatectomy for pancreas ductal adenocarcinoma (PDAC) remains controversial. The aim of this study was to identify the effect of R1 resection on recurrence pattern and survival after distal pancreatectomy for left‐sided PDAC. Methods Patients who underwent distal pancreatectomy for PDAC at two high‐volume institutions between January 2010 and December 2017 were retrospectively reviewed. Perioperative characteristics, pathological outcomes, recurrence pattern, and survival data were collected to compare R0 resection and R1 resection. Results Among 558 patients who underwent distal pancreatectomy for PDAC, 158 patients (28.3%) showed R1 resection margin. R1 patients were associated with large tumor size (3.3 cm vs. 3.7 cm, p = .006) and lower number of positive lymph nodes (1.3 vs. 2.0, p = .001). Median overall survival (37.3 months vs. 20.1 months, p < .001) and recurrence‐free survival (14.6 months vs. 6.9 months, p < .001) significantly differed between the R0 and R1 groups. Disease recurrence patterns were not statistically different between the two groups (p = .182). Among the recurrence patterns, peritoneal carcinomatosis had the shortest recurrence‐free survival (5.6 months, p < .05) and overall survival (13.6 months, p < .05) compared with all other recurrence patterns. Conclusions R1 resection margin after distal pancreatectomy was associated with poor survival and early recurrence. There is no significant difference in recurrence pattern between R0 and R1. Among the recurrence patterns, peritoneal carcinomatosis showed the worst prognosis.

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“…Proposed thresholds for RPD proficiency vary significantly between studies, with some studies recognizing notable improvements even after 200 cases [47,83] . Over the last decade, academic and highvolume centers have integrated robotic pancreas training programs into their training curriculum [84] . These efforts have helped strengthen the RPD technique in new surgeon graduates and overcome some initial trepidation towards minimally invasive pancreatic surgery.…”

Section: Robotic Pancreaticoduodenectomymentioning

confidence: 99%

Advances in pancreas surgery: robotic pancreaticoduodenectomy

Riachi¹,

Hewitt²

2023

Mini-invasive Surg

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Surgeon technical improvements made in the 1980s significantly decreased the morbidity and mortality associated with pancreaticoduodenectomy (PD). While minimally invasive surgery (MIS) is now the standard surgical approach for many benign and malignant pathologies, the technical complexity associated with PD presents many challenges to MIS adoption. However, advancements in robotic technology have done much to ameliorate mechanical impediments. Compared to laparoscopic surgery, the robotic platform provides surgeons with enhanced visualization, greater degrees of freedom and range of motion, tremor elimination, and superior ergonomic positioning. Although cost and availability concerns persist, training programs have increasingly incorporated robotic curricula, boosting the prevalence of robotic procedures, including robotic PD (RPD). While prospective data are limited, studies evaluating RPD demonstrate safety, equivalent short-term oncological outcomes, and longer operating times compared to open PD. Furthermore, exciting avenues exist for the future of RPD, ranging from continued instrument innovations to AI-enhanced adjuncts. Robotics has the potential to improve PD for patients and surgeons alike; however, further evaluation of oncologic and surgical outcomes requires well-powered, randomized, prospective trials to confirm the results of earlier retrospective studies, given the significant biases present. In this article, we review the progression of minimally invasive PD, present outcomes from studies evaluating RPD, and discuss areas of innovation for RPD.

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Impact of Resection Margin Status in Patients with Pancreatic Cancer: a National Cohort Study

Cited by 21 publications

References 26 publications

Distinct Stromal and Immune Features Collectively Contribute to Long-Term Survival in Pancreatic Cancer

Distinct Stromal and Immune Features Collectively Contribute to Long-Term Survival in Pancreatic Cancer

Effect of resection margin status on recurrence pattern and survival in distal pancreatectomy for left‐sided pancreatic ductal adenocarcinoma

Advances in pancreas surgery: robotic pancreaticoduodenectomy

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