Giuseppe Quero

Background: Minimally invasive surgery (MIS) is increasingly implemented for cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM). This systematic review and meta-analysis compared minimally invasive CRS/HIPEC (M-CRS/HIPEC) and open CRS/HIPEC (O-CRS/HIPEC) in terms of perioperative, postoperative, and long-term oncological outcomes. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched for comparative studies of M-CRS/HIPEC versus O-CRS/HIPEC in adult patients. Risk of bias was assessed using the Newcastle–Ottawa Scale and RoB 2.0. Pooled relative risks (RR) for dichotomous outcomes and standardized mean differences (SMD) for continuous outcomes were calculated with 95% confidence intervals (CI). Sensitivity analyses were performed to assess the potential influence of disease burden and primary tumor heterogeneity. Results: Twenty-one studies (1 randomized controlled trial and 20 retrospective cohorts) including 1184 patients (452 M-CRS/HIPEC and 732 O-CRS/HIPEC) were analyzed. Operative time did not differ between groups (SMD = 0.195; p = 0.667). Most cytoreductive procedures were comparable, although small bowel resections were less frequent with M-CRS/HIPEC (RR = 0.537; p = 0.018). The minimally invasive approach achieved higher CC0 rates (RR = 1.053; p = 0.045), with lower blood loss (SMD = −1.838; p < 0.001) and fewer transfusions (RR = 0.588; p = 0.002). Postoperative recovery favored M-CRS/HIPEC, with earlier return of bowel function and resumption of oral intake, shorter hospital stay, fewer readmissions, and earlier chemotherapy resumption (all p < 0.05). Overall and major morbidity were reduced, while postoperative mortality and 1-, 3-, and 5-year disease-free and overall survival did not differ significantly between groups. In the disease burden-restricted sensitivity analysis, differences in small bowel resection, CC0 rate, and 90-day readmission were no longer statistically significant, whereas the main perioperative and recovery benefits persisted. No significant differences in DFS or OS were identified in the additional sensitivity analyses at the evaluable time points. Conclusions: This meta-analysis supports a selective, expertise-driven use of M-CRS/HIPEC, offering perioperative and recovery advantages without significant differences in cytoreductive adequacy or long-term outcomes in appropriately selected patients.

Purpose: Robotic right hemicolectomy (RRH) has progressively emerged as a valid alternative minimally invasive approach to laparoscopic right hemicolectomy (LRH). Perioperative outcomes of RRH and LRH have been largely investigated. Aim of this study was to compare long-term survival outcomes in patients undergone RRH versus LRH for right-sided colon cancer. Methods: A systematic review and meta-analysis were performed searching PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing RRH versus LRH for right-sided colon cancer through December 2025 (PROSPERO registration: CRD420261372273). Risk of bias for non-randomized studies was assessed using the Newcastle–Ottawa Scale, while Cochrane Risk of Bias 2.0 was used for randomized controlled trials (RCT). Overall survival (OS) and disease-free survival (DFS) outcomes were pooled as hazard ratios (HRs) with 95% confidence intervals (CIs). Time-specific survival outcomes were analyzed as relative risks (RRs). Predefined subgroup analyses were performed for studies reporting complete mesocolic excision (CME), and sensitivity analyses were conducted in propensity score–matched (PSM) cohorts and contemporary-era studies. Results: Ten studies comprising 1,575 patients (716 RRH and 859 LRH) were included. Pooled time-to-event analyses demonstrated no significant difference between RRH and LRH in DFS (HR 0.91, 95% CI 0.72–1.15; P = 0.410) or OS (HR 1.11, 95% CI 0.84–1.41; P = 0.378). Similarly, no significant difference were observed in 1-, 3-, or 5-year DFS and OS analyses; however, all pooled RRs were consistently greater than 1, indicating a numerical trend favoring RRH. Finally, comparable outcomes were confirmed across CME studies, PSM cohorts, and studies representative of the contemporary robotic era. Conclusion: RRH provides long-term oncological outcomes comparable to those achieved with LRH for right-sided colon cancer. Despite the technical and perioperative advantages associated with robotic surgery, these did not translate into significant improvements in DFS or OS. These findings suggest that RRH represents a safe and oncologically sound alternative to laparoscopy providing comparable long-term oncological outcomes and suggesting possible additional benefits in favor of RRH.

Background: Gastric cancer (GC) remains a leading cause of cancer death worldwide. A subset of patients presents acutely with life-threatening complications such as perforation, obstruction, or bleeding, requiring surgery under suboptimal conditions. This multicenter Italian study aimed to explore outcomes of emergency GC surgery, identify prognostic factors, and compare survival across clinical presentations. Methods: Between 2013 and 2022, 263 GC patients presented emergently at two high-volume Italian centers. Among them, 90 patients with histologically proven adenocarcinoma who underwent emergency surgery were included. Primary outcomes were 30-day mortality and overall survival (OS). Results: Obstruction was the most frequent presentation (41.1%), followed by hemorrhage (34.4%) and perforation (24.4%). Severe complications (Clavien–Dindo ≥ 3) occurred in 28.8% of patients, and thirty-day mortality reached 13.3%. Median OS was 6.5 months. Diffuse-type GC predicted shorter OS than intestinal-type (5.5 vs. 14 months; p = 0.015). Radical surgery was performed in 63.3% of cases and was associated with superior OS compared with palliative procedures (14 vs. 4.5 months; p < 0.001). The clinical presentation did not influence survival. On exploratory multivariable analysis, advanced age and diffuse histology were associated with higher 30-day mortality, while gastric resection was associated with better OS. Conclusions: Emergency GC surgery carries high morbidity and mortality. Age, histology, and gastric resection were independent prognostic factors, whereas clinical presentation did not significantly affect survival. Early diagnosis and tailored perioperative strategies are needed to improve outcomes.

Background: Optimal long-term management after a first episode of uncomplicated acute diverticulitis (AD) remains debated. Quality of life (QoL) is increasingly recognized as a key outcome to guide individualized decision-making between clinical surveillance and elective sigmoid resection. Methods: This single-center prospective longitudinal observational study enrolled adults with a first episode of uncomplicated AD (Hinchey 0-1a). After recovery from the index episode, patients underwent either clinical follow-up (nonsurgery group) or elective laparoscopic sigmoidectomy (surgery group) according to routine clinical decision-making. Diverticulitis-specific QoL was assessed using the DV-QoL questionnaire, retrospectively referring to the month before the index episode and prospectively at 1, 6, and 12 months after post-episode management. The primary aim was to describe and compare DV-QoL trajectories between groups. A DV-QoL score ≥ 3.2 was used to define a non-acceptable symptom state (Patient Acceptable Symptom State (PASS) threshold). Predictors of non-acceptable QoL were explored in conservatively managed patients. Results: A total of 137 patients were included: 96 (70%) in the nonsurgery group and 41 (30%) in the surgery group. Baseline characteristics were comparable. Pre-episode DV-QoL scores were similar between groups (0.19 ± 0.29 versus 0.12 ± 0.33; p = 0.14). DV-QoL total scores were significantly higher (worse QoL) in the nonsurgery group at 1 month (2.60 ± 2.70 versus 0.11 ± 0.15; p < 0.001), 6 months (2.09 ± 2.24 versus 0.05 ± 0.12; p < 0.001), and 12 months (1.92 ± 2.07 versus 0.02 ± 0.07; p < 0.001). Non-acceptable QoL (PASS ≥ 3.2) occurred only in the non-surgery cohort at all timepoints, whereas no surgical patient exceeded PASS. Younger age independently predicted non-acceptable QoL in conservatively managed patients. Conclusions: Elective laparoscopic sigmoidectomy after a first uncomplicated AD episode was associated with sustained improvements in disease-specific QoL compared with clinical follow-up. Routine DV-QoL assessment may help identify patients at risk of persistent impairment and optimize individualized surgical decision-making.

Background: Robotic pancreatoduodenectomy (R-PD) has emerged as a minimally invasive alternative to open pancreatoduodenectomy (O-PD), although its role remains debated due to technical complexity and heterogeneous outcomes. This study compared perioperative outcomes between R-PD and O-PD in a high-volume center while minimizing the impact of the learning curve, and additionally evaluated the progressive improvement in surgical outcomes between the early and late phases of the robotic experience through comparative analyses and CUSUM assessment. Methods: A single-center propensity score–matched retrospective cohort study was conducted using a prospectively maintained database of patients undergoing PD between January 2020 and December 2025. The most recent 50 consecutive R-PDs (late group, LR-PD) were compared with O-PD after 2:1 matching (matched open group, MO-PD) to balance baseline characteristics. Perioperative, postoperative, and pathological outcomes were compared, and multivariable analyses were performed to identify independent predictors of key outcomes. A subgroup analysis comparing the first 50 R-PDs (early group, ER-PD) with the subsequent 50 cases (LR-PD) was also performed, along with CUSUM analyses of outcomes showing differences between the two phases of the robotic experience. Results: After matching, 100 MO-PD patients were compared with 50 LR-PD patients. LR-PD was associated with significantly lower estimated blood loss (EBL) (200 vs 300 mL; p = 0.0012) and shorter length of hospital stay (LOS) (12 vs 14 days; p = 0.038), but longer operative time (OT) (582 vs 362 minutes; p < 0.001). Rates of major complications (Clavien–Dindo ≥ III) and pancreas-specific complications were comparable between groups. A significantly lower incidence of postoperative lymphatic fistula was observed in the LR-PD (4 vs 15%; p = 0.045). At multivariable analysis, the LR-PD was independently associated with lower EBL ( β − 116.80; p = 0.023), shorter LOS ( β − 1.48; p = 0.041), and a reduced risk of postoperative lymphatic fistula (OR 0.30; p = 0.047), while remaining an independent predictor of longer OT ( β 99.75; p < 0.001). Within the R-PD, OT was significantly shorter in the LR-PD compared with the ER-PD (582 vs 705 minutes; p < 0.001). CUSUM analyses identified inflection points at cases 51, 55, and 53 for OT, major complications, and clinically relevant PPH, respectively. Conclusions: In a high-volume setting after the learning curve, R-PD is a potentially safe and feasible alternative to O-PD, offering reduced EBL, shorter LOS, and lower incidence of lymphatic fistula, despite longer OT. Further prospective studies are warranted to confirm these findings.

Type 2 diabetes mellitus is a multifactorial disease marked by progressive beta cell dysfunction; however, no reliable, easily measurable circulating biomarkers are currently available to track this decline. As microRNAs (miRNAs) tightly regulate beta cell physiology and are secreted and found in blood, we investigated whether specific circulating miRNAs reflect in vivo beta cell function in living donors. We conducted a cross-sectional study on two independent cohorts: a discovery cohort comprising 78 individuals with different levels of glucose tolerance [23 with normal glucose tolerance (NGT), 22 with impaired glucose tolerance (IGT) and 33 with type 2 diabetes] and a validation cohort comprising 158 individuals (71 non-diabetic individuals and 87 with type 2 diabetes) who were administered an oral glucose tolerance test (OGTT) and/or a mixed meal test (MMT) with measurement of glucose, insulin and C-peptide. We profiled plasma RNA by small RNA sequencing, and analysed differences between glucose tolerance groups using DESeq2. We used linear regression analyses to determine the association between miRNA abundance and clinical and metabolic measures. We validated selected miRNAs using droplet digital PCR (ddPCR). Finally, we specified a set of features that were used as an input for a LASSO model to select a biomarker signature that was able to estimate beta cell rate sensitivity (RS) values as a measure of beta cell function. We identified 11 miRNAs that were differentially expressed across the three glucose tolerance groups of the discovery cohort. Integrated analyses pinpointed a three-miRNA signature (miR-34a-5p, miR-1306-5p and miR-335-5p) that correlated with beta cell RS, which is an early indicator of insulin secretory impairment. We incorporated this panel of selected miRNAs with age and 1 h post-load glucose into a LASSO regression model that enabled discrimination of RS values (Spearman's ρ=0.43, p<0.05). We also confirmed model performance in an additional cohort of 71 non-diabetic individuals and 87 individuals with type 2 diabetes (Spearman's ρ=0.23, p<0.05). To provide proof of concept for potential clinical use, we substituted basal glucose for 1 h post-load glucose while retaining miRNA levels and age; this adaptation preserved the significance of the model in the discovery cohort (Spearman's ρ=0.46, p<0.05), and showed an interesting, but not significant, association in the validation cohort (Spearman's ρ=0.15, p=0.061). This three-miRNA signature combined with simple clinical parameters constitutes a promising biomarker for early beta cell dysfunction and type 2 diabetes progression that deserves further validation in additional cohorts.

Background Optimal long-term management after a first episode of uncomplicated acute diverticulitis (AD) remains debated. Quality of life (QoL) is increasingly recognized as a key outcome to guide individualized decision-making between clinical surveillance and elective sigmoid resection. Methods This single-center prospective longitudinal observational study enrolled adults with a first episode of uncomplicated AD (Hinchey 0-1a). After recovery from the index episode, patients underwent either clinical follow-up (non-surgery group) or elective laparoscopic sigmoidectomy (surgery group) according to routine clinical decision-making. Diverticulitis-specific QoL was assessed using the DV-QoL questionnaire, retrospectively referring to the month before the index episode and prospectively at 1, 6, and 12 months after post-episode management. The primary aim was to describe and compare DV-QoL trajectories between groups. A DV-QoL score ≥ 3.2 was used to define a non-acceptable symptom state (PASS threshold). Predictors of non-acceptable QoL were explored in conservatively managed patients. Results A total of 137 patients were included: 96(70%) in the non-surgery group and 41(30%) in the surgery group. Baseline characteristics were comparable. Pre-episode DV-QoL scores were similar between groups (0.19 ± 0.29 vs 0.12 ± 0.33; p = 0.14). DV-QoL total scores were significantly higher (worse QoL) in the non-surgery group at 1 month (2.60 ± 2.70 vs 0.11 ± 0.15; p < 0.001), 6 months (2.09 ± 2.24 vs 0.05 ± 0.12; p < 0.001), and 12 months (1.92 ± 2.07 vs 0.02 ± 0.07; p < 0.001). Non-acceptable QoL (PASS ≥ 3.2) occurred only in the non-surgery cohort at all time points, whereas no surgical patient exceeded PASS. Younger age independently predicted non-acceptable QoL in conservatively managed patients. Conclusion Elective laparoscopic sigmoidectomy after a first uncomplicated AD episode was associated with sustained improvements in disease-specific QoL compared with clinical follow-up. Routine DV-QoL assessment may help identify patients at risk of persistent impairment and optimize individualized surgical decision-making.

The online version contains supplementary material available at 10.1007/s13304-026-02598-7.

The mechanisms driving progressive β cell dysfunction in type 2 diabetes remain incompletely understood. This study aimed to identify pancreatic islet proteome changes that could predict diabetes onset. We isolated islets from individuals without diabetes undergoing partial pancreatectomy, previously characterized for glucose tolerance, insulin sensitivity, and insulin secretion, using laser capture microdissection, and analyzed them via high-performance liquid chromatography–mass spectrometry. Proteomic analysis revealed that individuals with impaired glucose tolerance (IGT) had reductions in proteins regulating glycolysis (PGK1, G3P), lipid metabolism (ACBP, ARF1), glucose transport (14-3-3B), and insulin secretion (STARD10, CAPDS) compared with normal glucose-tolerant (NGT) individuals. Additionally, IGT islets showed impaired expression of proteins involved in glucose- and incretin-stimulated insulin response (CREB1, IQGA1). Stratification by β cell glucose sensitivity (βGS) indicated that individuals with lower βGS exhibited reduced levels of insulin maturation (ERO1B) and antiapoptotic proteins (CASP8, PAK2, SKP1), along with increased SEL1L, a factor promoting endocrine precursor differentiation. These findings suggest that early defects in glucose metabolism and insulin secretion characterize IGT, while reduced βGS may trigger compensatory mechanisms, through enhanced β cell survival or neogenesis, to delay type 2 diabetes progression. Overall, proteomic alterations in prediabetic islets provide potential early predictive markers and targets for interventions aimed at preserving β cell function. This study provides novel insights into the molecular alterations in pancreatic islets associated with early β-cell dysfunction in non-diabetic individuals. Islet proteome of subjects with IGT showed early defects in glucose metabolism and insulin secretion. However, a decrease in beta-cell glucose sensitivity GS may induce compensatory mechanisms to delay progression to overt type 2 diabetes.