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.

Primary versus Revisional One Anastomosis Gastric Bypass - Outcomes of patients with at least eight-year follow-up.

BACKGROUND: One anastomosis gastric bypass (OAGB) prevalence is increasing worldwide and shows good mid- to long-term results. Data on long-term outcomes of revisional OAGB (rOAGB) is limited. This study objective is to evaluate the long-term outcomes of patients undergoing primary OAGB (pOAGB) and rOAGB. METHODS: A retrospective analysis of a prospectively maintained patient registry at a single-tertiary center. Patients undergoing OAGB from January 2015 to May 2016 were included and grouped to pOAGB and rOAGB. RESULTS: There were 424 patients, of which 363 underwent pOAGB, and 61 underwent rOAGB. Baseline characteristics were insignificantly different between groups except for type 2 diabetes (T2D) rate which was higher in pOAGB (26% vs. 11.5%, p=0.01). The mean follow-up time was 98.5±3.9 months and long-term follow up data was available for 52.5% of patients. The mean total weight loss (TWL) was higher in the pOAGB group (31.3±14 vs. 24.1±17.6, p=0.006), however TWL was comparable when relating to the weight at primary surgery for rOAGB. The rate of T2D and hypertension resolution was 79% and 72.7% with no difference between groups. 13 patients (5.9%) underwent OAGB revision during follow-up, with no difference between groups. Two deaths occurred during follow-up, both non-related to OAGB. CONCLUSION: OAGB is effective as a primary and as a revisional procedure for severe obesity with good long-term results in terms of weight loss and resolution of associated diseases. In addition, the revisional surgery rates and chronic complications are acceptable. Further large prospective studies are required to clarify this data.

Dysglycemia in non-functioning pancreatic neuroendocrine tumors (NF-PNET): Further insights into an under recognized entity.

Objective: Pancreatic neuroendocrine tumors (PNETs) are rare, but their incidence has risen significantly in recent years. Whereas diabetes mellitus (DM) is recognized in association with chronic pancreatitis and pancreatic cancer, it has not been well-characterized concerning non-functioning (NF)-PNETs.Study aim: to determine whether NF-PNETs are associated with DM/ Pre-DM and characterize the features of this putative association. Methods: Retrospective study to evaluate rate of Pre-DM /DM in subjects with NF-PNETs. Results: Study cohort of 129 patients with histologically confirmed NF-PNETs, ∼60% were men (M/F: 77/52). Abnormal glucose metabolism that preceded any treatment was seen in 70% of this cohort: overt DM in 34% and Pre-DM in 36% of the subjects. However, during follow-up, the overall prevalence rose to 80.6%, owing exclusively to newly diagnosed DM in subjects who received treatment.Patients with DM/Pre-DM were older (65 ± 11; 54 ± 14; p < 0.0001), the tumor was more commonly localized in the pancreatic body and tail (76.5% vs. 23.5% p = 0.03), while BMI (27 ± 6 vs. 28 ± 5 kg/m2), and tumor size (2.4 ± 2 vs. 2.9 ± 3.2 cm) were similar. The relative prevalence of DM in our cohort of NF-PNETs was 1.6 higher than that in the age and gender-adjusted general Israeli population (95 %CI: 1.197-2.212p = 0.03). Conclusions: We found a high rate of impaired glucose metabolism, either DM or Pre-DM, in a large cohort of NF-PNETs. The high prevalence of diabetes/pre-diabetes was unrelated to obesity or tumor size. This observation should increase awareness of the presence of DM on presentation or during treatment of "NF"-PNETs.

Adjuvant FOLFIRINOX in Patients with Resectable Pancreatic Cancer Is Effective but Rarely Feasible in Real Life: Is Neoadjuvant FOLFIRINOX a Better Option?

BACKGROUND: The recommended treatment for resectable pancreatic cancer (PC) is resection followed by adjuvant FOLFIRINOX. We assessed the proportion of patients that managed to complete the 12 courses of adjuvant FOLFIRINOX and compared their outcome with that of patients with borderline resectable pancreatic cancer (BRPC) who underwent resection after neoadjuvant FOLFIRINOX. METHODS: A retrospective analysis was performed on a prospectively maintained database of all PC patients who underwent resection with (2/2015-12/2021) or without (1/2018-12/2021) neoadjuvant therapy. RESULTS: A total of 100 patients underwent upfront resection, and 51 patients with BRPC received neoadjuvant treatment. Only 46 resection patients started adjuvant FOLFIRINOX, and only 23 completed 12 courses. The main reasons for not starting/completing adjuvant therapy were poor tolerance and rapid recurrence. Significantly more patients in the neoadjuvant group received at least six FOLFIRINOX courses (80.4% vs. 31%, p < 0.001). Patients who completed at least 6 courses, either pre- or postoperatively, had better overall survival (p = 0.025) than those who did not. In spite of having more advanced disease, the neoadjuvant group had comparable overall survival (p = 0.062) regardless of the number of treatment courses. CONCLUSION: Only a minority of patients (23%) undergoing upfront pancreatic resection completed the planned 12 courses of FOLFIRINOX. Patients who received neoadjuvant treatment were significantly more likely to receive at least six treatment courses. Patients receiving at least six courses had better overall survival than those who received fewer than six courses, regardless of the timing of treatment relative to surgery. Potential ways to increase chemotherapy adherence, such as administering treatment before surgery, should be considered.

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.

Microbiota transfer following liver surgery involves microbial extracellular vesicle migration that affects liver immunity.

BACKGROUND: Short-term perioperative administration of probiotics was shown to alleviate postoperative complications and promote liver recovery among patients undergoing resection for liver malignancy. The mechanisms by which probiotic bacteria effectively influence the gut microbiome composition during the perioperative time are controversial. Here, we aim to elucidate the short-term direct biological effect of probiotic microbiota-derived vesicles on host liver cells during the perioperative period. METHODS: Probiotic-derived vesicles (pbMVs) were administered postoperatively. pbMVs were isolated and characterized from probiotics, mainly from the bacteria genus Lactobacillus, Bifidobacterium, and Lactococcus. Mice underwent bile duct ligation, sham laparotomy (SHAM), or 70% partial hepatectomy (70%PH). pbMVs were tracked in vivo, and intrahepatic cellular and molecular aspects were analyzed by flow cytometry and qRT-PCR techniques. Liver sinusoidal endothelial cells (LSECs) analysis for Vascular Cell Adhesion Molecule-1(VCAM-1) expression following pbMV stimulation of cultured liver non-parenchymal cells which had been activated by LPS. RESULTS: The administered pbMV rapidly translocated to the liver after surgery. pbMV administrations following surgeries enhanced neutrophil clearance; there was a dramatic decline in the liver neutrophil-to-lymphocyte ratio Ly6G+/CD3+ and an increase in IL6 levels. pbMVs reduced intrahepatic VCAM1 and ICAM2 expression compared with control following SHAM and decrease in IL10 levels following 70%PH. The administration of pbMV improved liver regeneration 72 hours following surgical liver resection with a significant decrease in IL17 expression. pbMVs modulated VCAM-1 on liver sinusoidal endothelial cells in liver cell culture. CONCLUSIONS: Our study findings provide mechanistic insights into the liver-gut axis following surgery and illustrate how probiotic vesicles can reduce adhesion molecule expression and affect immune cell invasion and liver immunity, resulting in improved liver recovery following hepatic surgery.

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.

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.

A Lymph Node Ratio Model for Prognosis of Patients with Pancreatic Neuroendocrine Tumors.

The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS p = 0.002 HR = 13.4 and 5-year DFS p = 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS p = 0.004 HR = 9 and p = 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.

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.

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.

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.

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.

Ten-Year Results of Laparoscopic Sleeve Gastrectomy: a Retrospectively Designed Study of a Single Tertiary Center.

PURPOSE: Laparoscopic sleeve gastrectomy (SG) is the most popular bariatric surgery. Nonetheless, only a few studies have reported its long-term outcomes. This study aimed to evaluate changes in weight and body mass index (BMI) parameters, resolution of comorbidities, and frequency of re-operations in a follow-up period of at least 10 years. MATERIALS AND METHODS: Data was available from 180 patients' records who underwent SG between 2008 and 2011 in the Tel Aviv Sourasky Medical Center. Eighty patients agreed to partake in a follow-up assessment that was completed via a phone call questionnaire and hospital computed registry. RESULTS: Patients' mean preoperative BMI was 43.86 ± 6.36 kg/m2 which was significantly higher when compared to mean nadir BMI and last follow-up BMI (29.44 ± 7.12 and 36.34 ± 9.7; p < 0.001). Mean percentage of excess weight loss (%EWL) at 10 years was 42.65 ± 36.02% and mean percentage of total weight loss was 19.33 ± 16.73%. Twenty-eight patients (35%) maintained at least 50% EWL. Twenty-seven (33.75%) patients underwent at least one surgical procedure following SG. Eleven patients (13.75%) underwent a conversion to Roux-en-Y gastric bypass and six patients (7.5%) underwent conversion to one anastomosis gastric bypass. Resolution of type 2 diabetes (T2D), hypertension, and hypercholesterolemia occurred in 47%, 43.7%, and 48.4%, respectively. De-novo cases of gastroesophageal reflux (GERD) were present in 40%. CONCLUSION: SG shows high long-term failure rates. One of every three patients will undergo another surgical procedure within a 10-year period.

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.

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.

Revisional Surgery of One Anastomosis Gastric Bypass for Severe Protein-Energy Malnutrition.

BACKGROUND: One anastomosis gastric bypass (OAGB) is safe and effective. Its strong malabsorptive component might cause severe protein-energy malnutrition (PEM), necessitating revisional surgery. We aimed to evaluate the safety and outcomes of OAGB revision for severe PEM. METHODS: This was a single-center retrospective analysis of OAGB patients undergoing revision for severe PEM (2015-2021). Perioperative data and outcomes were retrieved. RESULTS: Ten patients underwent revision for severe PEM. Our center's incidence is 0.63% (9/1425 OAGB). All patients were symptomatic. Median (interquartile range) EWL and lowest albumin were 103.7% (range 57.6, 114) and 24 g/dL (range 19, 27), respectively, and 8/10 patients had significant micronutrient deficiencies. Before revision, nutritional optimization was undertaken. Median OAGB to revision interval was 18.4 months (range 15.7, 27.8). Median BPL length was 200 cm (range 177, 227). Reversal (n = 5), BPL shortening (n = 3), and conversion to Roux-en-Y gastric bypass (RYGB) (n = 2) were performed. One patient had anastomotic leak after BPL shortening. No death occurred. Median BMI and albumin increased from 22.4 kg/m2 (range 20.6, 30.3) and 35.5 g/dL (range 29.2, 41), respectively, at revision to 27.5 (range 22.2, 32.4) kg/m2 and 39.5 g/dL (range 37.2, 41.7), respectively, at follow-up (median 25.4 months, range 3.1, 45). Complete resolution occurs after conversion to RYGB or reversal to normal anatomy, but not after BPL shortening. CONCLUSIONS: Revisional surgery of OAGB for severe PEM is feasible and safe after nutritional optimization. Our results suggest that the type of revision may be an important factor for PEM resolution. Comparative studies are needed to define the role of each revisional option.