Primary Tumor Resection is Associated with Improved Disease-Specific Mortality in Patients with Stage IV Small Intestinal Neuroendocrine Tumors (NETs): A Comparison of Upfront Surgical Resection Versus a Watch and Wait Strategy in Two Specialist NET Centers.

INTRODUCTION: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. OBJECTIVE: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. METHODS: This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using 'institute' as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). RESULTS: A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I-III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. CONCLUSION: Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results.

Rising incidence of colorectal cancer in individuals younger than 50 years and increasing mortality from rectosigmoid cancer in England.

AIM: The aim was to describe changes in incidence and mortality from colorectal cancer (CRC) in England by analysing data available from the National Cancer Registration and Analysis Service (NCRAS, 2001-2017). METHODS: Data analysis was undertaken to interpret trends and patterns in age-standardized incidence and death rates from CRC, including sub-analyses by six age groups (0-24, 25-49, 50-59, 60-69, 70-79, 80+) and three sites of cancer-colonic, rectosigmoid and rectal. RESULTS: Overall CRC incidence remained relatively stable-70.1 cases per 100 000 individuals (95% CI 69.3-71.0) in 2001 and 68.8 cases (95% CI 68.0-69.5) in 2017. Sub-analysis demonstrates a quarter fewer incidence of rectosigmoid cancer (-27%). This is counterbalanced by a 3% rise in colon cancers. The age-standardized incidence rate of CRC increased by 59% in the 25-49 age group. In the over 50s, CRC incidence remained stable, with reductions seen in rectosigmoid cancer (50-59 years, -19%; 60-69, -26%; 70-79, -39%; 80+, -27%). Overall, mortality improved (-18.7%), primarily as a result of the reduction in deaths from colon (-31.6%) and rectal cancers (-25.1%). Deaths from the small incident number of rectosigmoid cancers, however, demonstrated a significant increase overall (+166.7%). Grouped age-standardized death rate analyses showed increasing death rates in the under 50s (+28.3%) compared to declining rates in the over 50s (-15.8%). CONCLUSIONS: There is a clear trend in increased incidence and mortality in individuals under 50 years old. There is also a trend to increased mortality from rectosigmoid cancer. These findings should have implications for national screening programme extension to under 50s and a call to arms for appropriate identification, staging and treatment of rectosigmoid cancers.

Laparoscopic Surgery Is Safe and Beneficial in True Functional High-Risk Patients with Colorectal Cancer: Utilization of Cardiopulmonary Exercise Test.

Background: Patients with colorectal cancer deemed to be high-risk may be denied an elective laparoscopic resection due to subjective reasons. A comparison of the 30-day outcomes in true functional high-risk patients who underwent either open or laparoscopic colorectal resection was undertaken. Materials and Methods: A retrospective cohort of all functional high-risk patients as assessed by cardiopulmonary exercise test between July 2015 and April 2018 were identified. Anaerobic threshold of <11 mL/kg/minute was used as a physiologic indicator to determine a high-risk patient. Adherence to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) was ensured. P values were computed via two-sided Fisher's exact test, and the exact Mann-Whitney U-test. Forest plots for relative risks with 95% confidence intervals were displayed on a log scale. Results: One hundred forty-six patients were identified as high-risk. Outcomes demonstrated a trend to laparoscopic benefit in all Clavien-Dindo grades of postoperative complications, but especially in severe complications of grades 3-4 (3.5% versus 10.2%). Readmissions demonstrated a trend to laparoscopic surgery benefit (7% versus 11.8%), as did mortality (1.7% versus 3.4%). The rate of surgery-site complications was higher after open surgery (42.1% versus 22.4%, P = .0201). Wound infections were observed more frequently after open surgery (12.5% versus 1.72%, P = .0280). The estimated risk of all-grade complications was significantly higher after open anterior rectal resection (63.0% versus 29.6%, P = .0281) and there was significantly shorter stay after laparoscopic right colectomy (5 v. 7 days, P = .0490). Conclusions: Laparoscopic approach for colorectal resections in high-risk patients is safe and beneficial compared to open surgery, especially in patients undergoing laparoscopic resection of the rectum and right colon.