Linking factors to incisional hernia following pancreatic surgery: a 14-year retrospective analysis.

BACKGROUND: Incisional hernias (IH) are a significant postoperative complication with profound implications for patient morbidity and healthcare costs. The relationship between IH and perioperative factors in pancreatic surgery, with particular attention to preoperative biliary stents and pancreatic fistulas requires further exploration. METHODS: This retrospective observational study examined adult patients who underwent open pancreatic surgeries via midline incision at a high-volume tertiary hepatopancreatobiliary center from January 2008 to December 2021. The study focused on IH incidence and associated risk factors, with particular attention to preoperative biliary stents and pancreatic fistulas. RESULTS: In a cohort of 620 individuals undergoing pancreatic surgery, 351 had open surgery with at least one-year follow-up. Within a median follow-up of 794 days (IQR 1694-537), the overall incidence of IH was 17.38%. The highest frequency of IH was observed among patients who had a Pancreaticoduodenectomy (PD). Significant predictors for the development of IH within the entire study population in a multivariable analysis included perioperative biliary stenting (OR 2.05; 95% CI 1.06-3.96; p = 0.03), increased age at diagnosis (OR 2.05; 95% CI 1.06-3.96; p = 0.01), and BMI (OR 1.08; 95% CI 1.01-1.15; p = 0.01). In the subset of patients who underwent Pancreaticoduodenectomy (PD), although the presence of biliary stents was associated with a heightened occurrence of SSIs, it did not demonstrate a direct correlation with an increased incidence of incisional hernias (IH). The development of pancreatic fistulas did not show a significant correlation with IH in either the Distal Pancreatectomy with Splenectomy (DPS) or the PD patient groups. CONCLUSIONS: The study underscores a notable association between biliary stent placement and increased IH risk after PD, mediated by elevated SSI incidence. Pancreatic fistulas were not directly correlated with IH in the studied cohorts. Further research is necessary to validate these findings and guide clinical practice.

Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.

Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as "second-hand" EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.

Implementation of artificial intelligence-based computer vision model in laparoscopic appendectomy: validation, reliability, and clinical correlation.

BACKGROUND: Application of artificial intelligence (AI) in general surgery is evolving. Real-world implementation of an AI-based computer-vision model in laparoscopic appendectomy (LA) is presented. We aimed to evaluate (1) its accuracy in complexity grading and safety adherence, (2) clinical correlation to outcomes. METHODS: A retrospective single-center study of 499 consecutive LA videos, captured and analyzed by 'Surgical Intelligence Platform,' Theator Inc. (9/2020-5/2022). Two expert surgeons viewed all videos and manually graded complexity and safety adherence. Automated annotations were compared to surgeons' assessments. Inter-surgeons' agreements were measured. Since 7/2021 videos were linked to patients' admission numbers. Data retrieval from medical records was performed (n = 365). Outcomes were compared between high and low complexity grades. RESULTS: Low and high complexity grades comprised 74.8 and 25.2% of 499 videos. Surgeons' agreements were high (76.9-94.4%, kappa 0.77/0.91; p < 0.001) for all annotated complexity grades. Surgeons' agreements were also high (96.0-99.8%, kappa 0.78/0.87; p < 0.001) for full safety adherence, whereas agreement was moderate in partial safety adherence and none (32.8-58.8%). Inter-surgeons' agreements were high for complexity grading (kappa 0.86, p < 0.001) and safety adherence (kappa 0.88, p < 0.001). Comparing high to low grade complexity, preoperative clinical features were similar, except larger appendix diameter on imaging (13.4 ± 4.4 vs. 10.5 ± 3.0 mm, p < 0.001). Intraoperative outcomes were significantly higher (p < 0.001), including time to achieve critical view of safety (29.6, IQR 19.1-41.6 vs. 13.7, IQR 8.5-21.1 min), operative duration (45.3, IQR 37.7-65.2 vs. 25.0, IQR 18.3-32.7 min), and intraoperative events (39.4% vs. 5.9%). Postoperative outcomes (7.4% vs. 9.2%) including surgical complications, mortality, and readmissions were comparable (p = 0.6), except length of stay (4, IQR 2-5.5 vs. 1, IQR 1-2 days; p < 0.001). CONCLUSION: The model accurately assesses complexity grading and full safety achievement. It can serve to predict operative time and intraoperative course, whereas no clinical correlation was found regarding postoperative outcomes. Further studies are needed.

Technical Considerations in One Anastomosis Gastric Bypass-the Israeli Society of Metabolic and Bariatric Surgery Experience.

BACKGROUND: One anastomosis gastric bypass (OAGB) is gaining popularity worldwide due to its safety and effectiveness. OAGB is the most commonly performed metabolic bariatric surgery (MBS) in Israel. Israel is the only country where OAGB is the most prevalent MBS. Our aim is to address OAGB technical aspects using a national survey completed by members of the Israeli Society of Metabolic and Bariatric Surgery (ISMBS). MATERIALS AND METHODS: An online-survey composed of a 17-item-based questionnaire was sent to ISMBS members. All responses were collected and analyzed. RESULTS: A total of 47/64 (73.4%) ISMBS members participated in the survey. Most surgeons (74.5%) had > 10 years of MBS experience, and most (61.7%) performed > 100 MBS/year. The majority (78.7%) perform OAGB as their most common procedure. Most surgeons fashion a 10-15-cm pouch and use a 36-Fr bougie, (57.4% and 38.3%). Regarding bowel length measurement, 70% use visual estimation and 10.6% routinely measure total small bowel length (TSBL). The most common reasons for creating a longer biliopancreatic limb (BPL) were high body mass index (BMI) and revisional surgery (83.3% and 66%, respectively). In a primary procedure of a patient with a BMI = 40, most (76.6%) would create a 150-200-cm BPL. In patients with a BMI > 50 or revisional cases, most (70.2% and 68.0%) would create a 175-225-cm BPL. CONCLUSION: OAGB is the most prevalent MBS performed in Israel. This survey showed common preferences and variations among ISMBS members. Further studies are needed in order to standardize and build a consensus on OAGB technique.

Two-hour indirect calorimetry measurement as a predictor of 24-hour energy expenditure in critically ill surgical patients: A longitudinal study.

BACKGROUND: Measuring energy expenditure (EE) by indirect calorimetry (IC) has become the gold standard tool for critically ill patients to define energy targets and tailor nutrition. Debate remains as to the optimal duration of measurements or the optimal time of day in which to perform IC. METHODS: In this retrospective longitudinal study, we analyzed results of daily continuous IC in 270 mechanically ventilated, critically ill patients admitted to the surgical intensive care unit in a tertiary medical center and compared measurements performed at different hours of the day. RESULTS: A total of 51,448 IC hours was recorded, with an average 24-h EE of 1523 ± 443 kcal/day. Night shift (00:00-8:00) was found to have significantly lower EE measurements (mean, 1499 ± 439 kcal/day) than afternoon (16:00-00:00; mean, 1526 ± 435 kcal/day) and morning (8:00-16:00; mean, 1539 ± 462 kcal/day) measurements (P < 0.001 for all). The bi-hourly time frame that most closely resembled the daily mean was 18:00-19:59, with a mean of 1521 ± 433 kcal/day. Daily EE measurements of the continuous IC at days 3-7 of admission showed a trend toward a daily increase in 24-h EE, but the difference was not statistically significant (P = 0.081). CONCLUSIONS: Periodic measurements of EE can differ slightly when performed at various hours of the day, but the error range is small and may not necessarily have a clinical impact. When continuous IC is not available, a 2-h EE measurement between 18:00 and 19:59 can serve as a reasonable alternative.

PET-CT underestimates the true pathological extent of disease at lymphadenectomy for melanoma patients after systemic therapy.

INTRODUCTION: Modern systemic therapy has revolutionized the treatment of melanoma. Currently, patients with clinically involved lymph nodes require lymphadenectomy with associated morbidities. Positron Emission Tomography - Computed Tomography (PET-CT) has demonstrated accuracy in melanoma detection and response to therapy. We aimed to identify whether a PET-CT directed lymphatic resection after systemic therapy is oncologically sound. MATERIALS AND METHODS: Retrospective review of patients who underwent lymphadenectomy after systemic therapy for melanoma with a preoperative PET-CT. Examined demographic, clinical, and perioperative parameters including extent of disease, systemic therapy and response, and PET-CT findings compared to pathological outcomes. We compared patients with "as or less than expected" outcomes on pathology against those with "more than expected" pathological outcomes. RESULTS: Thirty-nine patients met inclusion criteria. In 28 (71.8%), pathological outcomes were "as or less than expected" by PET-CT, and in 11 (28.2%) pathological outcome were "more than expected". "More than expected" occurred more frequently with advanced disease at presentation with 75% presenting with regional/metastatic disease versus only 42.9% in the "as or less than expected" group (p = 0.015). Poor response to therapy also trended towards the "more than expected" group with only 27.3% favorable response versus 53.6% favorable response in the "as or less than expected" group, not statistically significant. Extent of disease on imaging failed to predict pathological concordance. CONCLUSION: PET-CT underestimates pathological extent of disease in the lymphatic basin in 30% of patients after systemic therapy. We failed to identify predictors of more extensive disease and warn against limited PET-CT directed lymphatic resections.

The Effect of Revisional One Anastomosis Gastric Bypass After Sleeve Gastrectomy on Gastroesophageal Reflux Disease, Compared with Revisional Roux-en-Y Gastric Bypass: Symptoms and Quality of Life Outcomes.

BACKGROUND: Gastroesophageal reflux disease (GERD) is common after sleeve gastrectomy (SG). We aimed to evaluate the effect of revisional one anastomosis gastric bypass (OAGB) on GERD, compared with revisional Roux-en-Y gastric bypass (RYGB) METHODS: A retrospective single-center study of a prospectively maintained patient registry (2018-2022). All patients with GERD undergoing OAGB and RYGB after SG were retrieved and included in the study. RESULTS: Seventy-eight SG patients had conversion to OAGB (n=31) and RYGB (n=47). Baseline characteristics were similar except age (43.8±11.5 vs. 50.3±13.4 years; p=0.03), body mass index (39.9±8.8 vs. 30.6±6 kg/m2; p<0.001), time interval (8±2.7 vs. 6.4±3.4 years; p=0.01), and sleep apnea (29% vs 8.5%; p=0.01), respectively. There was no significant difference between groups in number of patients consuming proton pump inhibitors (70.1% vs. 72.3%; p=0.66), GERD-health-related quality of life (HRQL) score (9.6±7.2 vs. 13.1±8; p=0.06), and pathological endoscopic findings (48.4% vs. 46.8%; p=0.89). Major complication rates were 0% vs. 8.5% (p=0.09). At 32.4 months follow-up, total weight loss was 22%±12.9 and 4.4%±14.6 (p<0.001), GERD resolution 77.4% and 91.9% (p=0.03), HRQL scoring improved to 1.7±4.5 and 1.7±2.7; p=0.94 for OAGB and RYGB, respectively. CONCLUSIONS: SG conversion to RYGB provides better chances for definitive treatment of GERD. OAGB results in good symptom resolution and improved quality of life and may be considered for post-SG GERD treatment. The most appropriate solution should be individualized to each patient.

Ataxia Telangiectasia Mutated Signaling Delays Skin Pigmentation upon UV Exposure by Mediating MITF Function toward DNA Repair Mode.

Skin pigmentation is paused after sun exposure; however, the mechanism behind this pausing is unknown. In this study, we found that the UVB-induced DNA repair system, led by the ataxia telangiectasia mutated (ATM) protein kinase, represses MITF transcriptional activity of pigmentation genes while placing MITF in DNA repair mode, thus directly inhibiting pigment production. Phosphoproteomics analysis revealed ATM to be the most significantly enriched pathway among all UVB-induced DNA repair systems. ATM inhibition in mouse or human skin, either genetically or chemically, induces pigmentation. Upon UVB exposure, MITF transcriptional activation is blocked owing to ATM-dependent phosphorylation of MITF on S414, which modifies MITF activity and interactome toward DNA repair, including binding to TRIM28 and RBBP4. Accordingly, MITF genome occupancy is enriched in sites of high DNA damage that are likely repaired. This suggests that ATM harnesses the pigmentation key activator for the necessary rapid, efficient DNA repair, thus optimizing the chances of the cell surviving. Data are available from ProteomeXchange with the identifier PXD041121.

Comparison of One Anastomosis Gastric Bypass and Sleeve Gastrectomy for Revision of Laparoscopic Adjustable Gastric Banding: 5-Year Outcomes.

PURPOSE: Laparoscopic adjustable gastric banding (LAGB) is in continuous decline due to low effectiveness and high reoperation rates. This study aims to evaluate outcomes of converting LAGB to one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG) for insufficient weight loss or weight regain. MATERIALS AND METHODS: Retrospective comparative study, based on prospective registry database of a tertiary center (2012-2019). RESULTS: In all, 276 LAGB patients were converted to OAGB (n = 125) and SG (n = 151). Body mass index (BMI) at revision was 41.3 ± 6.6 and 42.3 ± 9.6 kg/m2 (P = 0.34) in OAGB and SG patients, respectively. Time interval was longer in OAGB patients (p < 0.001). Major early complication rates were comparable (2.4% and 4%; p = 0.46). At 5-years, OAGB patients had lower BMI (31.9 vs. 34.5 kg/m2; p = 0.002), and a higher total weight loss (25.1% vs. 18.8%; p = 0.003), compared with SG patients. Resolution of type 2 diabetes was higher in OAGB patients (93.3% vs. 66.6%; p = 0.047), while resolution of hypertension was not significantly different (84.6% and 80.5%; p = 0.68). Revision due to delayed complications was required in five (4%) OAGB patients and nine (8.6%) SG patients (p = 0.14). CONCLUSION: OAGB for revision after LAGB due to insufficient weight loss or weight regain is safe, and has better effectiveness in weight reduction and resolution of type 2 diabetes than SG.

Safety of concomitant cholecystectomy during one anastomosis gastric bypass compared with sleeve gastrectomy and Roux-en-Y gastric bypass.

Candidates of metabolic and bariatric surgery (MBS) are prone for gallstone formation. Concomitant cholecystectomy (CC) during MBS is controversial. This study is first to examine the safety of CC during one anastomosis gastric bypass (OAGB), compared with sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Single-center retrospective comparative study of CC (2012-2021) during OAGB, to SG and RYGB. CC was performed in 115 patients during OAGB (n = 50), SG (n = 39), and RYGB (n = 26). All procedures were completed laparoscopically. Baseline characteristics were similar except age, body mass index, gastroesophageal reflux disease, obstructive sleep apnea, and previous MBS (p < 0.05). Intraoperative complications occurred in one OAGB patient (2% vs. 0%, 0%; p = 0.52), which was not cholecystectomy related. There were no differences in total (6% vs. 2.6%, 15.4%; p = 0.13) and major (2% vs. 0%, 3.8; p = 0.50) early-complication rates. Of them, cholecystectomy-related complications occurred in one OAGB, compared with none of SG and one RYGB (2% vs. 0%, 3.8%; p = 0.50). The former was major, and the latter was minor complication. None of the OAGB patients needed re-admission (0% vs. 0%, 11.5; p = 0.04). All CC outcome parameters were similar between asymptomatic and symptomatic gallstones. Previous bariatric procedures were found to be a significant risk for major complications and readmissions (OR = 16.87, p = 0.019). CC during OAGB for gallstones seems safe, as in SG and RYGB. No cholecystectomy-related intraoperative complications occurred, and postoperative complication rates were low and acceptable. Outcomes for asymptomatic gallstones were similar to symptomatic ones, and we cautiously support CC in the presence of gallstones.

Immunological effects of heated intraperitoneal chemotherapy can be augmented by thymosin α1.

BACKGROUND: Peritoneal metastases of colorectal carcinoma origin (PM-CRC) are treated by cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC). However, the majority of patients recur, calling for novel treatments. We explored the immunogenic changes induced by HIPEC and the possibility to use thymosin α1 (Tα1) as an immune-stimulatory agent. METHODS: We used an experimental murine model of PM-CRC combined with mitomycin (MMC)-based HIPEC. We determined immune cell infiltration into tumor metastases after HIPEC administration by means of immunohistochemistry, and determined immunogenic cell death signals in tumor cells by real-time polymerase chain reaction. RESULTS: Mice with PM-CRC treated by HIPEC had increased overall survival (OS) compared to sham-treated mice (median OS 22.8 vs 18.9 days, respectively; P < 0.001). HIPEC induced increased infiltration of CD4+, CD8+, CD68 + and CD20 + cells into omental and visceral metastases at a magnitude of 40-100 %. We searched for potential immune signals induced by HIPEC by determining its effects on known immunogenic cell death proteins (heat-shock protein [HSP]-70, HSP-90 and calreticulin). HIPEC significantly increased HSP-90 mRNA expression (2.37 ± 1.5 vs 1-fold change, P < 0.05). The OS of Tα1 treated mice significantly improved compared to HIPEC-treated mice (16.3 ± 0.8 vs 14.1 ± 0.6 days, respectively, P = 0.02) and vs sham (11.8 ± 0.8 days, P = 0.007). CONCLUSIONS: HIPEC induced immunogenic changes that led to increased immune cell infiltration. These changes were further augmented by Tα1 treatment. Future studies aimed at optimizing Tα1 treatment should focus upon the immune response it evokes.

PD-1 Blockade Combined with Heated Intraperitoneal Chemotherapy Improves Outcome in Experimental Peritoneal Metastases from Colonic Origin in a Murine Model.

BACKGROUND: Heated intraperitoneal chemotherapy (HIPEC) was shown to induce immunogenicity of peritoneal metastases from colorectal cancer (PM-CRC) by induction of immunogenic cell death. We aimed to explore whether the addition of a checkpoint inhibitor would augment the effect of HIPEC in an experimental murine model of PM-CRC. METHODS: PM-CRC was established in C57BL mice by intraperitoneal inoculation of MC38 colon cancer cells. HIPEC was administered using the closed technique with mitomycin C (MMC). Clinical and immunological parameters were compared between animals treated with HIPEC alone and those treated with HIPEC + anti-programmed death receptor-1 (aPD-1). RESULTS: MMC-based HIPEC increased the overall survival of animals compared with sham-treated animals (22.8; 95% confidence interval [CI] 21.14-24.53 vs. 18.9 days; 95% CI 17.6-20.3, p < 0.001). The extent of peritoneal disease as measured by the modified peritoneal carcinomatosis index was also reduced by HIPEC. This clinical benefit was accompanied by increased infiltration of CD8+, CD68+, and CD20+ cells into tumor metastases in HIPEC-treated animals compared with sham-treated animals. We identified heat shock protein (HSP) 90 as a potential immunogenic cell death protein whose expression is increased under HIPEC conditions (fold change: 2.37 ± 1.5 vs. 1 without HIPEC, p < 0.05). Combined HIPEC + PD-1 treatment ameliorated survival compared with HIPEC alone and sham treatment (24.66; 95% CI 20.13-29.2 vs. 19; 95% CI 15.85-22.14 and 14.33 days; 95% CI 9.6-19.04, respectively; p = 0.008). This clinical effect was accompanied by increased CD8+ tumor infiltration. CONCLUSIONS: HIPEC induced the expression of immunogenic cell death signals that can support an anti-tumor immune response. This response can be further exploited by a checkpoint inhibitor.

One Anastomosis Gastric Bypass Compared with Sleeve Gastrectomy in Elderly Patients: Safety and Long-term Outcomes.

BACKGROUND: As life expectancy increases, more elderly patients are being considered for metabolic bariatric surgery. We aimed to assess the safety and long-term effectiveness of one anastomosis gastric bypass (OAGB) compared to sleeve gastrectomy (SG). METHODS: Single-center retrospective comparative study of OAGB and SG (2012-2019) in patients aged ≥ 65 years. RESULTS: In all, 124 patients underwent OAGB (n = 41) and SG (n = 83). Mean age was 67.6 ± 2.8 and 67.6 ± 2.6 years (p = 0.89), respectively. Baseline characteristics were comparable, except lower rates of hypertension (HTN) and non-alcoholic fatty liver disease in OAGB than SG patients (43.9% vs. 74.6%; p < 0.001, and 39.0% vs. 89.1%; p < 0.001, respectively). Body mass index (BMI) of OAGB and SG patients decreased from 41.8 ± 7.8 and 43.3 ± 5.9 kg/m2 (p = 0.25) to 28.6 ± 4.7 and 33.2 ± 5.3 (p < 0.001), at long-term follow-up, respectively. Excess weight loss (EWL) > 50% was achieved in 80.6% and 43.2% of OAGB and SG patients, with a mean EWL of 67.2% ± 22.3 and 45.8% ± 18.0 (p < 0.001) and a mean total weight loss (TWL) of 30.7% ± 10.4 and 21.9% ± 8.1 (p < 0.001), respectively. Resolution rates of obesity-associated medical problems were similar, except type 2 diabetes (T2D) and HTN, which were 86.6% and 73.3% in OAGB, compared with 29.7% and 36.3% in SG patients (p < 0.001 and p = 0.001), respectively. Major early complication rates were comparable (2.4% vs. 3.6%; p = 0.73, respectively). Revision for late complications was required in two OAGB patients. CONCLUSIONS: OAGB in the elderly is safe and results in better long-term weight reduction and resolution of T2D and HTN than SG.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

The Use of Inlay Bridge of the Posterior Fascia as Adjuvants to a Modified Rives-Stoppa Repair for Difficult Abdominal Wall Hernias.

BACKGROUND: Major abdominal wall defects remain a highly morbid complication. Occasionally a fascial defect is encountered, that despite all surgical efforts, is unable to completely approximate at the midline. Here we describe our method and outcomes of using a bridging mesh when the posterior fascia was unable to be approximated during the repair of large postoperative ventral hernias using the modified Rives-Stoppa technique. METHODS: A retrospective review was conducted looking at all the open abdominal wall hernia repairs between 2014 and 2020. The cohort of patients who had a bridge placed in addition to the traditional open modified Rives-Stoppa repair were used for this study. RESULTS: Nineteen patients had a mesh inlay bridge placed in addition to a modified Rives-Stoppa repair with a sublay (retrorectus) Ultrapro mesh. For the inlay mesh 13 Symbotex composite meshes were placed and 6 Vicryl meshes used. The average surface area of the defect was 358.1 cm^2. The average length of hospitalization was 8.8 days with a range of 3-24 days. During the immediate postoperative course there were 6 minor complications. During the follow-up period there were 2 recurrences. DISCUSSION: The use of inlay mesh bridge as an adjuvant to a modified Rives-Stoppa repair with a sublay ultrapro mesh is an effective technique for difficult abdominal wall repairs where the posterior fascia is unable to be approximated without tension.

Long-term outcomes of elderly patients with peritoneal metastases of colorectal origin after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) were reportedly safe for the elderly. However, long-term survival data in this subgroup of patients are scarce. Our aim was to evaluate the peri-operative and long-term outcomes of CRS + HIPEC in colorectal peritoneal metastases (CRC-PM) in patients ≥70 years of age. MATERIAL AND METHODS: We retrospectively analyzed our combined institutional databases for patients who underwent CRS + HIPEC for CRC-PM. Clinical and pathological characteristics, as well as overall survival (OS) and progression-free survival (PFS) were compared between the groups. Tumor extent was measured by the peritoneal carcinomatosis index (PCI) and completeness of cytoreduction by the CCR score. Major morbidity was defined according to Clavien-Dindo classification. RESULTS: The dataset of 159 patients included 33 elderly and 126 non-elderly patients. Clinical characteristics between the groups differed only in medical comorbidities (Charlson comorbidity index 10 vs. 7, P < 0.001) and delivery of post-HIPEC adjuvant treatment (12.5% vs. 43.8%, P = 0.004). Overall PCI and CCR0 rates were similar between the groups, as were length of stay and major morbidity and mortality rates. Long-term outcomes in the elderly group were lower than those of the non-elderly (median OS: 21.8 vs. 40.5 months, P < 0.001; median PFS: 6 vs. 8 months, P = 0.02, respectively). CONCLUSIONS: CRS + HIPEC in selected elderly patients can be safe in terms of postoperative morbidity and mortality. However, despite the same surgical extents and radicality, their long-term outcomes are inferior, possibly due to under-usage of systemic chemotherapy.

An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination.

Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of murine internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active human subject plasma demonstrated increased carbohydrate utilization following exercise. Epidemiologic data from a 20-year prospective study of a large human cohort of initially cancer-free participants revealed that exercise prior to cancer initiation had a modest impact on cancer incidence in low metastatic stages but significantly reduced the likelihood of highly metastatic cancer. In three models of melanoma in mice, exercise prior to cancer injection significantly protected against metastases in distant organs. The protective effects of exercise were dependent on mTOR activity, and inhibition of the mTOR pathway with rapamycin treatment ex vivo reversed the exercise-induced metabolic shield. Under limited glucose conditions, active stroma consumed significantly more glucose at the expense of the tumor. Collectively, these data suggest a clash between the metabolic plasticity of cancer and exercise-induced metabolic reprogramming of the stroma, raising an opportunity to block metastasis by challenging the metabolic needs of the tumor. SIGNIFICANCE: Exercise protects against cancer progression and metastasis by inducing a high nutrient demand in internal organs, indicating that reducing nutrient availability to tumor cells represents a potential strategy to prevent metastasis. See related commentary by Zerhouni and Piskounova, p. 4124.

Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma.

INTRODUCTION: Heated intraperitoneal chemotherapy (HIPEC) is currently implemented in the treatment of peritoneal metastases from colorectal carcinoma (PM-CRC) origin. However, recurrence is common and the effectiveness of HIPEC has been questioned. The aim of this study was to evaluate the use of thymosin alpha 1 (Tα1), an immunomodulatory molecule, as an adjuvant to HIPEC treatment. METHODS: We developed an experimental model of HIPEC by the induction of PM-CRC in C57BL mice and intra-abdominal perfusion of mitomycin C (MMC). Mice were treated with Tα1 at 0.6 mg/kg for 5 days after HIPEC. Clinical and immunological parameters were compared between HIPEC and HIPEC + Tα1 groups. RESULTS: Treatment with Tα1 increased overall survival of mice compared to HIPEC treatment alone and sham-treated animals (16.1 ± 0.8 vs. 14.1 ± 0.6 and 11.8 ± 0.8, respectively, p = 0.02). Tα1 had no direct anti-tumor effect, as seen by lack of inhibition of tumor cell proliferation. Tα1 treatment induced a T helper (Th) 1 immune response in tumor metastases as evidenced by a significant increase of the Th1-specific markers IFN-γ and T-bet (1.21 ± 0.3 vs. 0.52 ± 0.08, p < 0.05; 0.88 ± 0.04 vs. 0.64 ± 0.14, p < 0.05, respectively). This Th1 skew was accompanied by increased CD8+ infiltration into omental and visceral metastases by Tα1 treatment compared to sham and HIPEC-treated animals (21.24 ± 2.16 vs. 10.45 ± 0.89 and 7.7 ± 1.3, p < 0.001; 14.12 ± 1.54 vs. 12.12 ± 0.01 and 6.64 ± 0.87, p < 0.01, respectively). CONCLUSIONS: Tα1 augments the effect of HIPEC by the induction of a Th1 anti-tumor immune response. Further experiments should evaluate Tα1 and other novel immunomodulators in order to exploit the immunological opportunities created by HIPEC.

Gastric Cancer-Derived Extracellular Vesicles (EVs) Promote Angiogenesis via Angiopoietin-2.

Angiogenesis is an important control point of gastric cancer (GC) progression and metastasis. Angiopoietin-2 (ANG2) is a key driver of tumor angiogenesis and metastasis, and it has been identified in primary GC tissues. Extracellular vesicles (EVs) play an important role in mediating intercellular communication through the transfer of proteins between cells. However, the expression of ANG2 in GC-EVs has never been reported. Here, we characterized the EV-mediated crosstalk between GC and endothelial cells (ECs), with particular focus on the role of ANG2. We first demonstrate that ANG2 is expressed in GC primary and metastatic tissues. We then isolated EVs from two different GC cell lines and showed that these EVs enhance EC proliferation, migration, invasion, and tube formation in vitro and in vivo. Using an angiogenesis protein array, we showed that GC-EVs contain high levels of proangiogenic proteins, including ANG2. Lastly, using Lenti viral ANG2-shRNA, we demonstrated that the proangiogenic effects of the GC-EVs were mediated by ANG2 through the activation of the PI3K/Akt signal transduction pathway. Our data suggest a new mechanism via which GC cells induce angiogenesis. This knowledge may be utilized to develop new therapies in gastric cancer.