Michele Manara

Background/Objectives: The optimal surgical management of perforated gastric cancer (PGC) in emergency settings remains controversial. Urgent upfront one-stage gastrectomy (1SG) and two-stage gastrectomy (2SG) with damage-control surgery followed by elective gastrectomy have been proposed. The aim of the present systematic review is to compare short- and long-term outcomes between 1SG and 2SG in the treatment of PGC. Methods: A systematic review and individual patient data (IPD) meta-analysis of studies reporting data of patients undergoing 1SG vs. 2SG for PGC was conducted. The time-dependent effects of surgical interventions were assessed using a likelihood ratio test. Hazard function plots were generated via marginal prediction. Results: Ten retrospective series (579 patients) were included. Overall, 482 patients (83%) underwent 1SG, while 97 patients (17%) were treated with 2SG. A trend toward better short-term oncological outcomes and safety profiles for 2SG compared to 1SG was observed. Long-term outcomes were comparable between 1SG and 2SG, and the IPD meta-analysis showed no statistically significant difference between the two approaches in terms of OS or hazard for mortality at all time points. A trend towards a higher hazard for mortality was observed for 1SG in the first 20 months postoperatively. Conclusions: Our analysis suggests that 1SG and 2SG yield comparable short-term outcomes, although 2SG may be associated with a lower medium-term mortality risk. Further research is needed to identify key factors to improve clinical judgments and decision-making in PGC.

This systematic review aims to evaluate the current evidence regarding safety and efficacy of magnetic sphincter augmentation (MSA) for the treatment of gastroesophageal reflux disease (GERD) after laparoscopic sleeve gastrectomy (LSG). Conversion to Roux-en-Y gastric bypass (RYGB) carries the risk of surgical and metabolic complications and may be contraindicated in patients with normalized or near-normalized body mass index. The LINX™ procedure aims to restore LES competency and to repair the crura. We included 109 patients (14 studies) undergoing LINX™ implant after LSG. Median follow-up was 18.9 months (range 0.3–63). Both the GERD-HRQL (38 ± 13 vs. 10 ± 11; p = 0.0078) and daily PPI use (97.4% vs. 25.3%; p < 0.0001) were significantly improved. Overall, 31.8% of the patients experienced device-related adverse events, mainly self-limiting. LINX™ explant for esophageal erosion occurred in 0.9% of the patients.

Background/Objectives: Total gastrectomy (TG) is the cornerstone treatment for gastric cancer (GC). While open TG (OTG) with D2 lymphadenectomy remains the gold standard, alternative techniques such as lap-assisted TG (LATG), totally laparoscopic TG (TLTG), and robotic TG (RTG) have been reported with promising outcomes. The present analysis aimed to compare the short-term outcomes of different techniques for TG comprehensively in the setting of GC. Methods: A systematic review and network meta-analysis were performed. The primary outcomes were overall complications (OC), severe postoperative complications (SPCs), and anastomotic leak (AL). Pooled effect-size measures included risk ratio (RR), weighted mean difference (WMD), and 95% credible intervals (CrIs). Results: Sixty-eight studies (44,689 patients) were included. Overall, 52.4% underwent OTG, 6.5% LATG, 39.2% TLTG, and 1.9% RTG. Both TLTG (RR 0.82; 95% CrI 0.73–0.92) and RTG (RR 0.75; 95% CrI 0.59–0.95) showed a reduced rate of postoperative OC compared to OTG. SPCs and AL RR were comparable across all techniques. Despite the longer operative time, LATG, TLTG, and RTG showed reduced intraoperative blood loss, time to first flatus, ambulation, liquid diet resumption, and hospital stay compared to OTG. Conclusions: Minimally invasive approaches seem to be associated with improved OC and functional outcomes compared to OTG.

Background: Indocyanine Green (ICG) is a promising technique for the assessment of gastric conduit and anastomosis perfusion during esophagectomy. ICG integration may be helpful in minimizing the risk of anastomotic leak (AL). Literature evidence is sparse, while the real effect of ICG assessment on AL minimization remains unsolved. The aim of this systematic review and meta-analysis was to compare short-term outcomes between ICG-guided and non-ICG-guided (nICG) esophagogastric anastomosis during esophagectomy for cancer. Materials and Methods: PubMed, MEDLINE, Scopus, Web of Science, Cochrane Central Library, and ClinicalTrials.gov were queried up to 25 April 2024. Studies that reported short-term outcomes for ICG versus non-ICG-guided (nICG) anastomosis in patients undergoing esophagectomy were considered. Primary outcome was AL. Risk ratio (RR) and standardized mean difference (SMD) were utilized as effect size measures, whereas to assess relative inference we used 95% confidence intervals (95% CI). Results: Overall, 1399 patients (11 observational studies) were included. Overall, 576 (41.2%) underwent ICG gastric conduit assessment. The patients’ ages ranged from 22 to 91 years, with 73% being male. The cumulative incidence of AL was 10.4% for ICG and 15.4% for nICG. Compared to nICG, ICG utilization was related to a reduced risk for postoperative AL (RR 0.48; 95% CI 0.23–0.99; p = 0.05). No differences were found in terms of pulmonary complications (RR 0.83), operative time (SMD −0.47), hospital length of stay (SMD −0.16), or 90-day mortality (RR 1.70). Conclusions: Our study seems to indicate a potential impact of ICG in reducing post-esophagectomy AL. However, because of limitations in the design of the included studies, allocation/reporting bias, variable definitions of AL, and heterogeneity in ICG use, caution is required to avoid potential overestimation of the ICG effect.

Radical esophagectomy, including thoracic duct resection (TDR), has been proposed to improve regional lymphadenectomy and possibly reduce the risk of locor

Background: Thoracic duct ligation (TDL) during esophagectomy has been proposed to reduce the risk of postoperative chylothorax. Because of its role in immunoregulation, some authors argued that it had an unfavorable TDL effect on survival. The aim of this study was to analyze the effect of TDL on overall survival (OS). Methods: PubMed, MEDLINE, Scopus, and Web of Science were searched through December 2023. The primary outcome was 5-year OS. The restricted mean survival time difference (RMSTD), hazard ratios (HRs), and 95% confidence intervals (CI) were used as pooled effect size measures. The GRADE methodology was used to summarize the certainty of the evidence. Results: Five studies (3291 patients) were included. TDL was reported in 54% patients. The patients’ age ranged from 49 to 69, 76% were males, and BMI ranged from 18 to 26. At the 5-year follow-up, the combined effect from the multivariate meta-analysis is -3.5 months (95% CI −6.1, −0.8) indicating that patients undergoing TDL lived 3.5 months less compared to those without TDL. TDL was associated with a significantly higher hazard for mortality at 12 months (HR 1.54, 95% CI 1.38–1.73), 24 months (HR 1.21, 95% CI 1.12–1.35), and 28 months (HR 1.14, 95% CI 1.02–1.28). TDL and noTDL seem comparable in terms of the postoperative risk for chylothorax (RR = 0.66; p = 0.35). Conclusions: In this study, concurrent TDL was associated with reduced 5-year OS after esophagectomy. This may suggest the need of a rigorous follow-up within the first two years of follow-up.

Background. Minimally invasive surgery for the treatment of locally advanced gastric cancer (AGC) is debated. The aim of this study was to execute a comprehensive assessment of principal surgical treatments for resectable distal gastric cancer. Methods. Systematic review and randomized controlled trials (RCTs) network meta-analysis. Open (Op-DG), laparoscopic-assisted (LapAs-DG), totally laparoscopic (Lap-DG), and robotic distal gastrectomy (Rob-DG) were compared. Pooled effect-size measures were the risk ratio (RR), the weighted mean difference (WMD), and the 95% credible intervals (CrIs). Results. Ten RCTs (3823 patients) were included. Overall, 1012 (26.5%) underwent Lap-DG, 902 (23.6%) LapAs-DG, 1768 (46.2%) Op-DG, and 141 (3.7%) Rob-DG. Anastomotic leak, severe complications (Clavien–Dindo > 3), and in-hospital mortality were comparable. No differences were observed for reoperation rate, pulmonary complications, postoperative bleeding requiring transfusion, surgical-site infection, cardiovascular complications, number of harvested lymph nodes, and tumor-free resection margins. Compared to Op-DG, Lap-DG and LapAs-DG showed a significantly reduced intraoperative blood loss with a trend toward shorter time to first flatus and reduced length of stay. Conclusions. LapAs-DG, Lap-DG, and Rob-DG performed in referral centers by dedicated surgeons have comparable short-term outcomes to Op-DG for locally AGC.

Background. Severe postoperative complications (SPCs) may occur after curative esophagectomy for cancer and are associated with prolonged hospital stay, augmented costs, and increased in-hospital mortality. However, the effect of SPCs on survival after esophagectomy is uncertain. Aim. To assess the impact of severe postoperative complications (SPCs) on long-term survival following curative esophagectomy for cancer, we conducted a systematic search of PubMed, MEDLINE, Scopus, and Web of Science databases up to December 2023. The included studies examined the relationship between SPCs and survival outcomes, defining SPCs as Clavien–Dindo grade > 3. The primary outcome measure was long-term overall survival (OS). We used restricted mean survival time difference (RMSTD) and 95% confidence intervals (CIs) to calculate pooled effect sizes. Additionally, we applied the GRADE methodology to evaluate the certainty of the evidence. Results. Ten studies (2181 patients) were included. SPCs were reported in 651 (29.8%) patients. The RMSTD overall survival analysis shows that at 60-month follow-up, patients experiencing SPCs lived for 8.6 months (95% Cis −12.5, −4.7; p < 0.001) less, on average, compared with no-SPC patients. No differences were found for 60-month follow-up disease-free survival (−4.6 months, 95% CIs −11.9, 1.9; p = 0.17) and cancer-specific survival (−6.8 months, 95% CIs −11.9, 1.7; p = 0.21). The GRADE certainty of this evidence ranged from low to very low. Conclusions. This study suggests a statistically significant detrimental effect of SPCs on OS in patients undergoing curative esophagectomy for cancer. Also, a clinical trend toward reduced CSS and DFS was perceived.

Pulmonary complications (PC) are common after esophagectomy and their impact on long-term survival is not defined yet. The present study aimed to assess the effect of postoperative PCs on long-term survival after esophagectomy for cancer. Systematic review of the literature through February 1, 2023, was performed. The included studies evaluated the effect of PC on long-term survival. Primary outcome was long-term overall survival (OS). Cancer-specific survival (CSS) and disease-free survival (DFS) were secondary outcomes. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. Eleven studies were included (3423 patients). Overall, 674 (19.7%) patients developed PC. The RMSTD analysis shows that at 60-month follow-up, patients not experiencing PC live an average of 8.5 (95% CI 6.2–10.8; p < 0.001) months longer compared with those with PC. Similarly, patients not experiencing postoperative PC seem to have significantly longer CSS (8 months; 95% CI 3.7–12.3; p < 0.001) and DFS (5.4 months; 95% CI 1.6–9.1; p = 0.005). The time-dependent HRs analysis shows a reduced mortality hazard in patients without PC at 12 (HR 0.6, 95% CI 0.51–0.69), 24 (HR 0.64, 95% CI 0.55–0.73), 36 (HR 0.67, 95% CI 0.55–0.79), and 60 months (HR 0.69, 95% CI 0.51–0.89). This study suggests a moderate clinical impact of PC on long-term OS, CSS, and DFS after esophagectomy. Patients not experiencing PC seem to have a significantly reduced mortality hazard up to 5 years of follow-up. Graphical abstract

Background: Debate exists concerning the impact of D2 vs. D1 lymphadenectomy on long-term oncological outcomes after gastrectomy for cancer. Methods: PubMed, MEDLINE, Scopus, and Web of Science were searched and randomized controlled trials (RCTs) analyzing the effect of D2 vs. D1 on survival were included. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were assessed. Restricted mean survival time difference (RMSTD) and 95% confidence intervals (CI) were used as effect size measures. Results: Five RCTs (1653 patients) were included. Overall, 805 (48.7%) underwent D2 lymphadenectomy. The RMSTD OS analysis shows that at 60-month follow-up, D2 patients lived 1.8 months (95% CI −4.2, 0.7; p = 0.14) longer on average compared to D1 patients. Similarly, 60-month CSS (1.2 months, 95% CI −3.9, 5.7; p = 0.72) and DFS (0.8 months, 95% CI −1.7, 3.4; p = 0.53) tended to be improved for D2 vs. D1 lymphadenectomy. Conclusions: Compared to D1, D2 lymphadenectomy is associated with a clinical trend toward improved OS, CSS, and DFS at 60-month follow-up.