Eleftherios Makris

Surgical Considerations in the Management of Gastric Adenocarcinoma

Since Theodor Billroth and César Roux perfected the methods of postgastrectomy reconstruction in as early as the late nineteenth century, surgical management of gastric cancer has made incremental progress. The longstanding and contentious debate on the optimal extent of lymph node dissection for gastric cancer seems to have settled in favor of D2 dissection. Pylorus-preserving distal (central) gastrectomy has emerged as a less invasive, function-preserving option for T1N0 middle-third gastric cancers. Frozen section analysis of margins seems partially helpful in this direction. Last, the role of palliative gastrectomy in patients with metastatic seems less important than initially thought.

Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the U.S. Neuroendocrine Tumor Study Group

The risk of recurrence after resection of non‐metastatic gastro‐entero‐pancreatic neuroendocrine tumors (GEP‐NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative‐intent resection.

Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection

Background: The incidence, clinical characteristics, and long‐term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized. Methods: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8‐institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease‐free survival were compared among patients with and without carcinoid syndrome. Results: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative‐intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease‐free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64–1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis. Conclusion: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease‐free survival or overall survival.

Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group

Background: The impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long‐term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin. Methods: Patients who underwent curative‐intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence‐free survival were analyzed relative to surgical margin status using univariable and multivariable analyses. Results: Among 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence‐free survival (10‐year recurrence‐free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2–2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0–3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0–1.7, P = .060). In contrast, margin status was not associated with overall survival (10‐year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6–6.2, P = .001) and recurrence‐free survival (hazard ratio 2.6, 95% confidence interval 1.4–5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor‐specific factors, such as cellular differentiation, perineural invasion, Ki‐67 index, and major vascular invasion, rather than surgical margin, were associated with long‐term outcomes. Conclusion: Margin status was not associated with long‐term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal‐sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.