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.

Surgical Intelligence can Lead to Higher Adoption of Best Practices in Minimally Invasive Surgery.

OBJECTIVE: To examine the use of surgical intelligence for automatically monitoring critical view of safety (CVS) in laparoscopic cholecystectomy (LC) in a real-world quality initiative. BACKGROUND: Surgical intelligence encompasses routine, AI-based capture and analysis of surgical video, and connection of derived data with patient and outcomes data. These capabilities are applied to continuously assess and improve surgical quality and efficiency in real-world settings. METHODS: LCs conducted at two general surgery departments between December 2022 and August 2023 were routinely captured by a surgical intelligence platform, which identified and continuously presented CVS adoption, surgery duration, complexity, and negative events. In March 2023, the departments launched a quality initiative aiming for 75% CVS adoption. RESULTS: 279 procedures were performed during the study. Adoption increased from 39.2% in the 3 pre-intervention months to 69.2% in the final 3 months (P < .001). Monthly adoption rose from 33.3% to 75.7%. Visualization of the cystic duct and artery accounted for most of the improvement; the other two components had high adoption throughout. Procedures with full CVS were shorter (P = .007) and had fewer events (P = .011) than those without. OR time decreased following intervention (P = .033). CONCLUSION: Surgical intelligence facilitated a steady increase in CVS adoption, reaching the goal within 6 months. Low initial adoption stemmed from a single CVS component, and increased adoption was associated with improved OR efficiency. Real-world use of surgical intelligence can uncover new insights, modify surgeon behavior, and support best practices to improve surgical quality and efficiency.

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.

Long-term outcomes and patterns of recurrence in patients with thin melanoma and a negative sentinel lymph node biopsy: a single-center experience.

The majority of patients diagnosed with melanoma have thin melanomas (≤1 mm). Data on the rate and pattern of recurrence after a negative sentinel lymph node biopsy (SLNB) are sparse. We retrospectively searched our institutional database and retrieved the records of patients with thin melanomas who underwent an SLNB with negative results. We analyzed patterns of recurrence, time to recurrence, and mode of diagnosis. Thirteen of the 198 patients with thin melanomas and negative SLNB results had tumor recurrence (6.5%): two local in transit (15.4%), three regional (21.3%), and eight distant (61.5%). Distant recurrences tended to occur later than local or regional ones [median disease-free survival = 50 months (95% confidence interval: 36.1-63.9) vs. 34 and 15 months (95% confidence interval: 5.4-24.6), P = 0.005, respectively]. The percentage of patients with tumor thickness ≥0.8 mm was higher among those who sustained recurrence (84.6 vs. 64.9% for no recurrence, P = 0.04). The majority of patients with recurrence were not being followed up when diagnosed (69%), and they are presented because of clinical symptoms. Patients with recurrence had lower survival compared with those without recurrence (median: 118 months vs. ongoing survival, P < 0.001, respectively). Melanoma recurrence in patients with thin melanomas and negative SLNBs is rare, tends to be distant, and negatively affects prognosis. Recurrence tends to occur in patients with melanoma thickness ≥0.8 mm. Further studies are needed to identify patients with high recurrence risk and determine optimal follow-up protocols.

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.

Esophagogastric cancer surgery characteristics and outcomes in bariatric patients, compared with non-bariatric patients.

BACKGROUND: The association between bariatric surgery and esophagogastric cancer (EGC) is debated. This study aimed to assess EGC characteristics and surgery outcomes comparing bariatric and non-bariatric patients. METHODS: Single-center retrospective analysis of prospective EGC surgery database. RESULTS: EGC-surgery was performed in 269 patients, classified as bariatric (N.=10, 3.3%), and non-bariatric (N.=259, 96.6%) groups. Non-bariatric group was sub-classified into body mass index (BMI) <35 kg/m2 (N.=244) and >35 kg/m2 (N.=15). BMI was 35.3±5.6 vs. 25.7±16.1 and 37.8±8.7 kg/m2 in bariatric vs. non-bariatric-BMI <35 and >35, respectively (P<0.001). Bariatric patients were significantly younger (56.75±11 vs. 71±10 and 68.38±8.2 years; P<0.001). They tended to have lower rates of diabetes mellitus (30% vs. 43.9% and 73.3%; P=0.05) and significantly lower hypertension rates (50%, vs.86.5% and 93.3%, P<0.004). Bariatric procedures were performed 11.3 years (IQR 5.5-16.5) prior to EGC-surgery. Tumor characteristics were statistically comparable except a significantly higher number of positive LN in the bariatric group (6.9±13.6 vs. 2.7±4.9 and 1.9±4.8; P=0.006), and more bariatric patients received adjuvant treatment (P=0.035). Postoperative major complication rates (0% vs. 25.8%, and 33.3%; P=0.14) and length of hospital stay (14.1±15.3, vs. 23±28.5, and 21±18 days; P=0.59) were comparable. There was no significant difference in Disease- free survival (P=0.42) or overall survival (P=0.48) between patient-groups. CONCLUSIONS: Bariatric patients were diagnosed with EGC at a younger age, and tended to have worse nodal involvement. Although outcomes were comparable, clinical and endoscopic surveillance seem important as EGC can occur 10 years or earlier than in non-bariatric patients.

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.