The Near-infrared Visualization and Pre-emptive Ligation of the Thoracic Duct Effectively Reduce the Chyle Leak Incidence After Minimally Invasive Esophagectomy.

OBJECTIVE: The aim of the present study is to assess the effectiveness of indocyanine-green (ICG)-guided lymphography (ICG-Lg) in reducing the incidence of chyle leak (CL) after esophagectomy. BACKGROUND: Chylothorax may severely impact esophageal cancer surgery, and the pre-emptive ligation of the thoracic duct (TD) is the most widespread control of this complication. Intraoperative ICG-Lg has been recently embedded in minimally invasive esophagectomy to facilitate TD detection and pre-emptive ligation. METHODS: This retrospective analysis included consecutive patients who underwent minimally invasive Ivor Lewis esophagectomy for cancer at a tertiary referral center between January 2018 and August 2023. Patients were routinely submitted to extended lymphadenectomy with TD ligation and removal. All patients treated after January 2021 underwent ICG-Lg for TD identification and ligation (ICG group) and compared to the previous series (no-ICG group). The primary outcome was the incidence of postoperative CL, while univariate and backward stepwise multivariate logistic regression models were performed to identify associated factors. RESULTS: After including 320 patients, 151 (ICG group) were submitted to ICG-Lg before the pre-emptive TD ligation. Both groups presented similar characteristics, except for neoadjuvant therapy (P=<0.001) and preoperative comorbidities (P=0.045). Intraoperative ICG-Lg significantly reduced the incidence of postoperative CL (11.8% vs 4.6%, P=0.026) and was significantly associated with shorter median length of hospital stay (13 vs 9 days, P=0.006). However, CL after ICG-Lg was more likely to require repairing reoperation (P=0.050). CONCLUSIONS: Intraoperative ICG-Lg demonstrated significantly lower rates of CL after total minimally invasive esophagectomy and, therefore, it should be routinely embedded in the standardized surgical technique of high-volume centers for esophageal cancer.

Implementing protocol-based relaparoscopy for severe complications in laparoscopic colorectal surgery.

BACKGROUND: Although laparoscopy has demonstrated growing applications for either primary colorectal resections or reoperations, no standardized criteria for implementing laparoscopy in revisional surgery have been reported. This study analyzes a single-center series of major complications after laparoscopic colorectal surgery, undergoing laparoscopic (LR), or open reoperations in compliance with a hemodynamics-based institutional management. METHODS: This study retrospectively analyzes a series of consecutive patients who primarily underwent either laparoscopic left colectomy or low anterior resection in a tertiary referral center between 2016 and 2021. Major complications requiring reoperation (MCR) were managed through an interdisciplinary protocol and submitted to reoperation according to patient hemodynamics and intra-abdominal contamination. A cohort analysis primarily assessed treatment failure rates (i.e., 90-day mortality and need for further surgery), while postoperative morbidity was secondarily examined. RESULTS: Out of 1137 laparoscopic colorectal resections, 497 patients met eligibility criteria, while 45 (9.1%) developed MCRs were managed according to the standardized interdisciplinary protocol. Revisional surgery was performed through either LR (66.7%) or (33.3%). Treatment failure was 13.3% overall, including additional surgery (11.1%) and 90-day mortality (6.6%) after reoperation. In both overall and anastomotic leak-specific MCRs, relaparoscopy resulted in minimized length of hospital stay, postoperative morbidity, and intensity of care. CONCLUSIONS: Relaparoscopy for MCR preserves clinical benefits related to minimally invasive colorectal surgery. Further studies should investigate applicative determinants and impediments related to the center volume.

Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells.

OBJECTIVE: Colorectal tumours are often densely infiltrated by immune cells that have a role in surveillance and modulation of tumour progression but are burdened by immunosuppressive signals, which might vary from primary to metastatic stages. Here, we deployed a multidimensional approach to unravel the T-cell functional landscape in primary colorectal cancers (CRC) and liver metastases, and genome editing tools to develop CRC-specific engineered T cells. DESIGN: We paired high-dimensional flow cytometry, RNA sequencing and immunohistochemistry to describe the functional phenotype of T cells from healthy and neoplastic tissue of patients with primary and metastatic CRC and we applied lentiviral vectors (LV) and CRISPR/Cas9 genome editing technologies to develop CRC-specific cellular products. RESULTS: We found that T cells are mainly localised at the front edge and that tumor-infiltrating T cells co-express multiple inhibitory receptors, which largely differ from primary to metastatic sites. Our data highlighted CD39 as the major driver of exhaustion in both primary and metastatic colorectal tumours. We thus simultaneously redirected T-cell specificity employing a novel T-cell receptor targeting HER-2 and disrupted the endogenous TCR genes (TCR editing (TCRED)) and the CD39 encoding gene (ENTPD1), thus generating TCREDENTPD1KOHER-2-redirected lymphocytes. We showed that the absence of CD39 confers to HER-2-specific T cells a functional advantage in eliminating HER-2+ patient-derived organoids in vitro and in vivo. CONCLUSION: HER-2-specific CD39 disrupted engineered T cells are promising advanced medicinal products for primary and metastatic CRC.

Impact of powered circular stapler on anastomotic leak after anastomosis to the rectum: a propensity score matched study.

PURPOSE: The aim of the present study is to assess the impact of Echelon Circular™ powered stapler (PCS) on left-sided colorectal anastomotic leaks and to compare results to conventional circular staplers (CCS). METHODS: A single center cohort study was carried out on 552 consecutive patients, who underwent laparoscopic colorectal resection and anastomosis to the rectum between December 2017 and September 2022. Patients who underwent powered circular anastomosis to the rectum were matched to those who had a conventional stapled anastomosis using a propensity score matching. Main outcomes were anastomotic leak (AL) rate, anastomotic bleeding, and postoperative outcomes. RESULTS: After adjusting cases with propensity score matching, two new groups of patients were generated: 145 patients in the PCS and 145 in the CCS. The two groups were homogeneous with respect to demographics and comorbidities on admission. Overall, AL occurred in 21 (7.3%) patients. No significant differences were observed with respect to AL (5.5% in PCS vs 9% in CCS; p = 0.66), fistula severity (p = 0.60) or reoperation rate (p = 0.65) in the two groups in study. A higher rate of anastomotic bleeding was observed in the CCS vs PCS (5.5% vs 0.7%, p = 0.03). At univariate analysis performed after propensity score matching, stapler diameter ≥ 31mm and age ≥ 70 years were the only variable significantly associated with anastomotic leak (p = 0.001 and p = 0.031; respectively). CONCLUSIONS: The powered circular stapler has no impact on AL, while it could affect bleeding rate at the anastomotic site.

Protective ileostomy creation after anterior resection of the rectum: Shared decision-making or still subjective?

AIM: The choice of whether to perform protective ileostomy (PI) after anterior resection (AR) is mainly guided by risk factors (RFs) responsible for the development of anastomotic leakage (AL). However, clear guidelines about PI creation are still lacking in the literature and this is often decided according to the surgeon's preferences, experiences or feelings. This qualitative study aims to investigate, by an open-ended question survey, the individual surgeon's decision-making process regarding PI creation after elective AR. METHOD: Fifty four colorectal surgeons took part in an electronic survey to answer the questions and describe what usually led their decision to perform PI. A content analysis was used to code the answers. To classify answers, five dichotomous categories (In favour/Against PI, Listed/Unlisted RFs, Typical/Atypical, Emotions/Non-emotions, Personal experience/No personal experience) have been developed. RESULTS: Overall, 76% of surgeons were in favour of PI creation and 88% considered listed RFs in the question of whether to perform PI. Atypical answers were reported in 10% of cases. Emotions and personal experience influenced surgeons' decision-making process in 22% and 49% of cases, respectively. The most frequently considered RFs were the distance of the anastomosis from the anal verge (96%), neoadjuvant chemoradiotherapy (88%), a positive intraoperative leak test (65%), blood loss (37%) and immunosuppression therapy (35%). CONCLUSION: The indications to perform PI following rectal cancer surgery lack standardization and evidence-based guidelines are required to inform practice. Until then, expert opinion can be helpful to assist the decision-making process in patients who have undergone AR for adenocarcinoma.

Endoscopic vacuum therapy versus self-expandable metal stent for treatment of anastomotic leaks < 30 mm following oncologic Ivor-Lewis esophagectomy: a matched case-control study.

BACKGROUND: Management of anastomotic leaks after Ivor-Lewis esophagectomy remains a challenge. Although intracavitary endoscopic vacuum therapy (EVT) has shown great efficacy for large dehiscences, the optimal management of smaller leaks has not been standardized. This study aims to compare EVT versus self-expandable metal stent (SEMS) in the treatment of leaks < 30 mm in size, due to the lack of current data on this topic. METHODS: Patients undergoing EVT (cases) or SEMS (controls) between May 2017 and July 2022 for anastomotic leaks < 3 cm following oncologic Ivor-Lewis esophagectomy were enrolled. Controls were matched in a 1:1 ratio based on age (± 3 years), BMI (± 3 kg/m2) and leak size (± 4 mm). RESULTS: Cases (n = 22) and controls (n = 22) showed no difference in baseline characteristics and leak size, as per matching at enrollment. No differences were detected between the two groups in terms of time from surgery to endoscopic treatment (p = 0.11) or total number of procedures per patient (p = 0.05). Remarkably, the two groups showed comparable results in terms of leaks resolution (90.9% vs. 72.7%, p = 0.11). The number of procedures per patient was not significant between the two cohorts (p = 0.05). The most frequent complication in the SEMS group was migration (15.3% of procedures). CONCLUSION: EVT and SEMS seem to have similar efficacy outcomes in the treatment of anastomotic defects < 30 mm after Ivor-Lewis esophagectomy. However, larger studies are needed to corroborate these findings.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.

Applicative Limitations of Indocyanine Green Fluorescence Assistance to Laparoscopic Lymph Node Dissection in Total Gastrectomy for Cancer.

BACKGROUND: Indocyanine green (ICG) fluorescence has been recently introduced as a novel imaging technique improving the accuracy of lymph node (LN) dissection in gastric cancer (GC) surgery, although procedure standardization and achievements have not been clearly defined. This study analyzed the feasibility and effectiveness of ICG-guidance for laparoscopic D2-lymphadenectomy during total gastrectomy for cancer. METHODS: This study retrospectively analyzed a single-center series of patients who underwent laparoscopic total gastrectomy for cancer between April 2015 and August 2021. All patients underwent surgery with standard D2 LN dissection. Intraoperative ICG-fluorescence was institutionally implemented in April 2018 and was performed routinely afterward. Primary outcomes were LN harvest and ratio. Secondary endpoints included operative time and subgroup analysis to assess variables potentially affecting LN retrieval. RESULTS: The study population included 102 patients, and ICG-fluorescence was applied in 38 (37.3%). ICG and no-ICG groups presented similar median age, gender proportions, ASA score and comorbidities (age-adjusted Charlson Comorbidity Index), body mass index, and advanced pathological stage. The median of LNs retrieved was significantly higher after the intraoperative ICG-guidance (44 vs. 32; p = 0.004), although this association was not significant after neoadjuvant therapy or among patients with positive LNs. Lymph node ratio and operative time were not significantly impacted by ICG fluorescence. Multivariate analysis identified the ICG-assistance as the only independent determinant for LN harvest (p = 0.029). CONCLUSIONS: ICG-guidance contributes to a significantly wider LN retrieval after laparoscopic D2-lymphadenectomy during total gastrectomy for cancer. However, neoadjuvant therapy and positive LN stage appeared to limit the procedural effectiveness to ICG-assisted LN identification.

Diet and Lifestyle Habits in Early-Onset Colorectal Cancer: A Pilot Case-Control Study.

BACKGROUND: Early-onset colorectal cancer (eoCRC), defined as a colorectal cancer (CRC) in patients younger than 50 years old, shows an increasing incidence worldwide in the latest years. The role of exogenous factors associated with CRC has been largely overlooked in eoCRC. Here, we conducted a case-control study to evaluate the diet and the lifestyle habits in an Italian population of patients with eoCRC, compared to age-matched healthy controls (HCs). METHODS: We enrolled 118 subjects (47 cases, 71 controls) in a third-level academic hospital. We analyzed epidemiological features (age, sex, body mass index), lifestyle behaviors (smoking habits, physical activity, type of diet, use of dietary supplements), and eating habits (semiquantitative food-frequency questionnaire) in eoCRCs and HCs, covering the previous 5 years. RESULTS: In our cohort, positive family history of CRC was significantly associated with the development of eoCRC (p = 0.004). Fresh meat (p = 0.003), processed meat (p < 0.001), dairy products (p = 0.013), and smoking (p = 0.0001) were significantly associated with eoCRC compared to controls. Other variables did not differ significantly between the two groups. CONCLUSION: Fresh and processed meat, dairy products, and smoking could be considered significant risk factors for eoCRC, although further confirmation by international multicenter studies is desirable. Diet and smoking could be the main areas of future interventions for eoCRC primary prevention.

Risk factors for anastomotic leakage after anterior resection for rectal cancer (RALAR study): A nationwide retrospective study of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group.

AIM: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage. METHODS: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured. RESULTS: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection. CONCLUSIONS: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction.