Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. National Institute for Health and Care Research.

Background: Minimally invasive surgery in obese patients is still challenging, so exploring one more item in this research field ranks among the main goals of this research. We aimed to compare short-term postoperative outcomes of open and video-laparoscopic (VL) approaches in CRC obese patients undergoing colorectal resection. Methods: We performed a retrospective analysis of a surgical database including 138 patients diagnosed with CRC, undergoing VL (n = 87, 63%) and open (n = 51, 37%) colorectal surgery. As a first step, propensity score matching was performed to balance the comparison between the two intervention groups (VL and open) in order to avoid selection bias. The matched sample (N = 98) was used to run further regression models in order to analyze the observed VL surgery advantages in terms of postoperative outcome, focusing on hospitalization and severity of postoperative complications, according to the Clavien–Dindo classification. Results: The study sample was predominantly male (N = 86, 62.3%), and VL was more frequent than open surgery (63% versus 37%). The two subgroup results obtained before and after the propensity score matching showed comparable findings for age, gender, BMI, and tumor staging. The specimen length and postoperative time before discharge were longer in open surgery (OS) patients; the number of harvested lymph nodes was higher than in VL patients as well (p < 0.01). Linear regression models applied separately on the outcomes of interest showed that VL-treated patients had a shorter hospital stay by almost two days and about one point less Clavien–Dindo severity than OS patients on average, given the same exposure to confounding variables. Tumor staging was not found to have a significant role in influencing the short-term outcomes investigated. Conclusion: Comparing open and VL surgery, improved postoperative outcomes were observed for VL surgery in obese patients after surgical resection for CRC. Both postoperative recovery time and Clavien–Dindo severity were better with VL surgery.

Background: The mortality rate following pancreaticoduodenectomy (PD) has been decreasing over the past few years; nonetheless, the morbidity rate remains elevated. The most common complications after PD are post-operative pancreatic fistula (POPF) and delayed gastric emptying (DGE) syndrome. The issue as to which is the best reconstruction method for the treatment of the pancreatic remnant after PD is still a matter of debate. The aim of this study was to retrospectively analyze the morbidity rate in 100 consecutive PD reconstructed with Wirsung-Pancreato-Gastro-Anastomosis (WPGA), performed by a single surgeon applying a personal modification of the pancreatic reconstruction technique. Methods: During an 8-year period (May 2012 to March 2020), 100 consecutive patients underwent PD reconstructed with WPGA. The series included 57 males and 43 females (M/F 1.32), with a mean age of 68 (range 41–86) years. The 90-day morbidity and mortality were retrospectively analyzed. Additionally, a systematic review was conducted, comparing our technique with the existing literature on the topic. Results: We observed eight cases of clinically relevant POPF (8%), three cases of “primary” DGE (3%) and four patients suffering “secondary” DGE. The surgical morbidity and mortality rate were 26% and 6%, respectively. The median hospital stay was 13.6 days. The systematic review of the literature confirmed the originality of our modified technique for Wirsung-Pancreato-Gastro-Anastomosis. Conclusions: Our modified double-layer WPGA is associated with a very low incidence of POPF and DGE. Also, the technique avoids the risk of acute hemorrhage of the pancreatic parenchyma.

Background: Minimally invasive methods in colorectal surgery offer unquestionable advantages, especially in the context of obesity. The current study addresses the lack of scientific evidence on the long-term oncologic safety of video-laparoscopic (VL) approaches in excess-weight CRC patients undergoing surgery. Methods: We retrospectively analyzed a surgical database consisting of 138 CRC patients undergoing VL (n = 87, 63%) and open CRC surgery (n = 51, 37%). To reduce selection bias, a propensity score matching was applied as a preliminary step to balance the comparison between the two surgery groups, i.e., VL and open surgery. Data from patients treated by the same surgeon were used.to minimize bias. Additional Cox regression models were run on the matched sample (N = 98) to explore the observed benefits of VL surgery in terms of overall and cancer-free survival. The nonparametric Kaplan-Meier method was used to compare the two surgical approaches and assess the likelihood of survival and cancer relapse. Results: The study sample was mostly male (N = 86, 62.3%), and VL outnumbered open surgery (63% versus 37%). Both before and after the matching, the VL-allocated group showed better overall survival (p < 0.01) with comparable cancer-free survival over more than five years of median observation time (66 months). Kaplan Meier survival probability curves corroborated the VL significant protective effect on survival (HR of 0.32; 95% CI: 0.13 to 0.81) even after adjusting for major confounding factors (age, gender, comorbidity index, BMI, tumor localization, tumor staging, tumor grading, clearance, CRM). Findings on oncologic performance by tumor relapse were comparable but lacked significance due to the small number of events observed. Conclusions: Comparing CRC surgical approaches, VL allocation showed comparable cancer-free survival but also a better performance on overall mortality than open surgery over more than five years of median observation.

Inorganic polyphosphate (iPolyP) is a ubiquitous molecule composed of a variable number of orthophosphate units. Recent studies have highlighted its involvement in colorectal cancer (CRC) cell proliferation. However, further investigations are needed to elucidate its role in CRC cell progression and migration, as well as its influence on the tumor microenvironment. This study focuses on the inorganic polyphosphate (iPolyP)/transient receptor potential cation channel subfamily M member 8 (TRPM8) axis and its impact on CRC progression. To investigate these issues, western blotting, fixed and live cells immunofluorescence, 2D and 3D cell culture on CRC-patient derived tissues, ELISA, and wound healing assays were performed. Our results show that inorganic polyphosphate induces the expression of epithelial-to-mesenchymal transition (EMT) markers in CRC cells. Furthermore, the iPolyP/TRPM8 axis indirectly promotes tumor growth through activation of the Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain-containing protein 3 (NLRP3) inflammasome in immune cells, leading to increased levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the tumor microenvironment (TME), thereby advancing CRC. These findings suggest that targeting the iPolyP/TRPM8 pathway may be a promising strategy to inhibit CRC progression and metastasis.

Irisin is a myokine that enhances insulin secretion and β cell viability in both rodent and human β cells. Here, we investigated whether irisin preserves β cell functional mass in vivo in diabetic mice and ex vivo in human pancreatic islets from subjects with type 2 diabetes (T2D). In mice made diabetic by a high-fat diet and streptozotocin, irisin administration improved glycemic homeostasis by increasing islet insulin content and glucose-stimulated insulin secretion while also markedly stimulating β cell proliferation. In islets from T2D subjects, which typically display substantial structural and functional impairments, irisin restored insulin content and glucose-stimulated insulin secretion. Mechanistic studies in INS-1E cells showed that chronic exposure to high glucose blunted glucose-triggered cytoplasmic calcium increases, essential for insulin secretion. Under these glucotoxic conditions, while irisin was unable to activate CREB and AKT, it induced AMPK-mTORC1-S6K–dependent mobilization of endoplasmic reticulum calcium stores, resulting in enhancement of insulin secretion. Overall, these findings highlight irisin’s multifaceted ability to counteract β cell failure in experimental and human T2D.