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Suzy E Meijer,1,2 Olga Klebanov-Akopyn,3 Vera Pavlov,2,3 Shachar Laks,4 David Hazzan,4 Aviram Nissan,2– 4 Douglas Zippel3,4 1Department of Infectious Disease, Sourasky Medical Center, Tel Aviv, Israel; 2The Surgical Oncology Laboratory, Hadassah-Hebrew University Hospital, Jerusalem, Israel; 3The Surgical Oncology Laboratory, The Chaim Sheba Medical Center, Ramat Gan, Israel; 4Department of General and Oncological Surgery – Surgery C, The Chaim Sheba Medical Center, Ramat Gan, IsraelCorrespondence: Douglas ZippelDepartment of General & Oncological Surgery-Surgery C, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, IsraelTel +972-3-530-2714Fax +972-3-5341562Email dov.zippel@sheba.health.gov.ilPurpose: Minimal residual disease (MRD) refers to micrometastases that are undetectable by conventional means and is a potential source of disease relapse. This study aimed to detect the presence of breast cancer (BC) biomarkers (MGB-1, MGB-2, CK-19, NY-BR-1) using real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMC) of BC patients and the impact of a positive assay on clinical outcome.Patients and Methods: Patients in the analysis included females > 18 years of age with biopsy-proven carcinoma of the breast. A 10 mL sample of venous blood was obtained from 10 healthy controls and 25 breast cancer patients. Comparisons of peripheral blood markers were made with clinicopathological variables.Results: High-quality RNA was extracted from all samples with a mean RNA concentration of 224.8± 155.3 ng/μL. Each of the molecular markers examined was highly expressed in the primary breast tumors (n = 3, positive controls) with none of the markers detected in healthy negative controls. The NY-BR-1 marker was expressed in one (4%) patient with metastatic disease with no MGB-1 and MGB-2 detected in any sample derived from the study patients. The CK-19 marker was detected in 16 (64%) of the BC cases. No correlation was found between CK-19 expression and tumor stage (P = 0.07) or nodal status (P = 0.32). No correlation was identified in the BC patients between CK-19 expression and receptor status in the BC primary tumor.Conclusion: This study showed high expression of all 4 markers NY-BR-1, MGB-1, MGB-2 and CK-19 in the PBMCs derived from breast cancer patients. CK-19 was detected in 64% of the stage I–III cases operated with curative intent, the only recurrent events occurring in the CK-19-positive cases. Our data confirm the need to enhance techniques for detection of MRD, which may better predict patients at risk for relapse.Keywords: breast cancer, circulating tumor cells, cancer biomarkers, early detection, predictive potential

Purpose: Several international groups have published guidelines to identify low-risk breast cancer (BC) patients who are eligible for partial breast irradiation (PBI). These include the American Society for Radiation Oncology (ASTRO), the European Society for Radiotherapy and Oncology (ESTRO), and ESTRO subgroups such as the Intraoperative radiation (IORT) Task Force and Groupe Européen de Curiethérapie (GEC) -ESTRO. Only ASTRO guidelines recommend against the use of PBI in known carriers of germline pathogenic variants (PVs) in BRCA1/2. The aim of this study was to evaluate the proportion of BC patients, subsequently found to be BRCA1/2 PV carriers who would be eligible for PBI based on clinical-pathologic criteria of the above-mentioned international guidelines., Methods and Materials: Data were extracted from the medical records of consecutive BC BRCA1/2 PV carriers treated at a single institution between 2006 and 2023. Data included patient demographics, tumor characteristics, treatment, and disease outcomes., Results: Overall, 498 patients with 518 primary tumors were analyzed. Of these, 282 (12 of them with synchronous bilateral disease) presented with unknown genetic status at diagnosis and formed the study cohort. The median age at diagnosis was 42.7 years (range, 23.8-77.9). Based on the recent ASTRO guidelines (not including conditionally recommended criteria), 17 of 294 (5.8%) of the carriers had tumors that would be eligible for PBI, including 3 Her2-positive tumors and 5 patients diagnosed between ages 40 and 49 years. Using the ESTRO IORT and the ACROP-ESTRO PBI criteria, 9 of 294 (3%) would be eligible, whereas with the GEC-ESTRO low-risk criteria, 31 of 294 (10.5%) of the carriers would be eligible, and their intermediate risk criteria would increase eligibility for PBI by an additional 8.2% (overall 18.7%)., Conclusions: Using clinical-pathologic criteria published in international guidelines, 3% to 18% of BRCA1/2 PV carriers will have tumors eligible for PBI. Therefore, especially in populations who are at high risk for being BRCA1/2 PV carriers, we recommend adhering to stricter guidelines. In our cohort, ASTRO, ESTRO-IORT, and ESTRO PBI had the lowest probability of identifying BRCA1/2 PV carriers as eligible for PBI., Competing Interests: Disclosures The authors disclose the following relationships/activities/interests (none related to the content of the manuscript): Rinat Bernstein-Molho received honoraria for lectures from Astra Zeneca, Roche, and Pfizer and support for attending meetings from Pfizer. Einav Nili Gal-Yam received honoraria for lectures from Astra Zeneca, Roche, Pfizer, Novartis, Gilead, Menarini, MSD, and Eli-Lilly and support for attending meetings from Pfizer, Roche, and Gilead. The remaining authors declare no conflicts of interest., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the rate of axillary node-positive disease in patients with early breast cancer who had a suspicious axillary lymph node on radiation planning computed tomography (CT)., Methods and Materials: A retrospective review was conducted of the medical records of all patients with breast cancer who were referred for axillary ultrasound from the radiation unit to the breast imaging unit at the Meirav Breast Center, Sheba Medical Center, from 2012 to 2022. Ethics approval was obtained. Only the records of patients who were referred due to an abnormal axillary lymph node seen on radiation planning CT were further evaluated., Results: During the study period, a total of 21 patients were referred to the breast imaging unit for evaluation of suspicious nodes seen on radiation planning CT. Of these, 3 cases were excluded. A total of 15 out of the 18 (83%) patients included had an abnormal lymph node in the ultrasound, and an ultrasound-guided biopsy was recommended (BI-RADS 4). Of these, 3 (out of 15, 20%) had a positive biopsy for tumor cells from the axillary lymph node. Two were cases after primary systemic therapy without complete pathologic response. Thickening of the lymph node cortex and complete loss of the central fatty hilum were associated with pathologic lymph node., Conclusion: Sonar had limited ability to differentiate reactive nodes from involved nodes. The presence of lymph nodes with loss of cortical-hilum differentiation on ultrasound together with clinical features are parameters that can help guide the need of further biopsy. Histopathology evaluation is important to make the diagnosis of residual axillary disease. Future studies and guidelines are needed to improve the diagnostic abilities and reduce the number of patients who are undergoing biopsy for noninvolved nodes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The contribution of clinical breast exam (CBE) to breast cancer diagnosis in average risk women undergoing regular screening mammography is minimal. To evaluate the role of CBE in high-risk women, we compared BC diagnosis by CBE in BRCA mutation carriers undergoing regular BC surveillance to average to intermediate risk women undergoing regular breast cancer screening., Methods: A retrospective chart review of all consecutive screening visits of BRCA mutation carriers (January 2012-October 2022) and average to intermediate risk women (November 2016-December 2022) was completed. Women with histologically confirmed BC diagnosis were included. Additional CBE yield for BC diagnosis, defined as the percentage of all BC cases detected by CBE alone, was assessed in both groups., Results: Overall, 12,997 CBEs were performed in 1,328 BRCA mutation carriers in whom 134 BCs were diagnosed. In 7,949 average to intermediate risk women who underwent 15,518 CBEs, 87 BCs were diagnosed. CBE contributed to BC diagnosis in 3 (2%) BRCA mutation carriers and 3 (4%) non-carriers. In both groups, over 4,000 CBEs were needed in order to diagnose one cancer. In all 3 BRCA mutation carriers BC was palpated during the surveillance round that did not include MRI. In the average to intermediate risk group, 2 of 3 cancers diagnosed following CBE findings were in a different location from the palpable finding., Conclusions: The contribution of CBE to BC diagnosis is marginal for all women including BRCA mutation carriers. In BRCA mutation carriers, CBE appears redundant during the MRI surveillance round., (© 2024. The Author(s).)

Background: Although minimally invasive surgery for Crohn's disease has been validated in previous studies, most of those reports have referred to laparoscopic-assisted procedures with an extra-corporeal anastomosis., Objectives: To evaluate the short- and long-term outcomes of total laparoscopic ileocolic resection with an intracorporeal anastomosis for Crohn's disease patients., Methods: We conducted a single-center retrospective review of all patients who underwent primary ileocolic resection for Crohn's disease between 2010 and 2021. Group A included 34 patients who underwent total laparoscopic ileocolic resection with intracorporeal anastomosis. Group B comprised 144 patients who underwent an open or laparoscopic-assisted procedure., Results: No differences were noted in operative time (mean 167 minutes vs. 152 minutes, P = 0.122), length of stay (median 6.4 days vs. 7.5 days, P = 0.135), readmission rates (11.8% vs. 13.2%, P = 1), and microscopic involvement of surgical margins (7.7% vs. 18.5%, P = 0.249). Group A had significantly fewer postoperative surgical site infections (2.9% vs. 22.2% respectively, P = 0.013), with no differences in other complications prevalence. After a median follow-up of 46 months, there were similar rates of endoscopic recurrence (47.1% vs. 51.4%, P = 0.72), clinical recurrence (35.3% vs. 47.9%, P = 0.253), and surgical recurrence (2.9% vs. 4.9%, P = 0.722)., Conclusions: Total laparoscopic ileocolic resection with intracorporeal anastomosis for Crohn's disease is safe and resulted in favorable outcomes in terms of postoperative wound healing. The long-term disease recurrence rates were like those of laparoscopic-assisted and open ileocolic resection.

Background: The peritoneum is a common metastatic site of colorectal cancer (CRC) and associated with worse oncological outcomes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve outcomes in selected patients. Studies have demonstrated significant difference in survival of patients with primary colon and rectal tumors both in local and in metastatic setting; but only few assessed outcomes of CRS/HIPEC for rectal and colon tumors. We studied the perioperative and oncological outcomes of patients undergoing CRS/HIPEC for rectal cancer., Methods: A retrospective analysis of a prospectively maintained database between 2009 and 2021 was performed., Results: 199 patients underwent CRS/HIPEC for CRC. 172 patients had primary colon tumors and 27 had primary rectal tumors. Primary rectal location was associated with longer surgery (mean 4.32, hours vs 5.26 h, p = 0.0013), increased blood loss (mean 441cc vs 602cc, p = 0.021), more blood transfusions (mean 0.77 vs 1.37units, p = 0.026) and longer hospitalizations (mean 10 days vs 13 days, p = 0.02). Median disease-free survival (DFS) was shorter in rectal primary group; 7.03 months vs 10.9 months for colon primaries (p = 0.036). Overall survival was not statistically significant; 53.2 months for rectal and 60.8 months for colon primary tumors. Multivariate analysis indicated origin (colon vs rectum) and Peritoneal Cancer Index to be independently associated with DFS., Conclusions: Patients with rectal carcinoma undergoing CRS/HIPEC for peritoneal metastasis had worse peri-operative and oncological outcomes. Overall survival was excellent in both groups. This data may be used for risk stratification when considering CRS/HIPEC for patients with rectal primary., (© 2023. The Society for Surgery of the Alimentary Tract.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Breast cancer diagnosis had been linked to an increased risk of melanoma in several reports. The aim of the current study was to assess the role of genetics, increased surveillance, and radiation treatment in patients with a dual diagnosis of breast cancer and melanoma (DBM)., Materials and Methods: All patients treated at Sheba Medical Center between 2007 and 2021 with DBM were included in the cohort. Data on family history, genetic tests, characteristics, and treatment of both cancers were collected. The proportion of patients with a pathogenic variant (PV) in BRCA1 and BRCA2 genes was compared to a control group of patients with breast cancer. The proportion of patients presenting with in-situ disease was compared to the national registry data., Results: The cohort included 222 DBM patients of whom 114 had documentation of genetic testing. Twenty patients tested positive for PVs of which 13 (11%) were in BRCA genes. This was comparable to the proportion in patients with a diagnosis of breast cancer (736; 19%). The proportion of melanoma diagnosed at stage 0 was comparable to the national proportion ( N  = 40; 30% vs. 28%, respectively). In comparison to the national registry, a larger proportion of breast cancers were ductal carcinoma in situ or lobular carcinoma in situ [10% in the registry vs. 19% (22) in the cohort; P  < 0.003]., Conclusions: In patients with DBM we did not find an increased proportion of PVs in BRCA genes. Our findings suggest that the increased standardized incidence ratio of the dual diagnosis may be partially explained by increased surveillance and detection of earlier-stage cancers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Retroperitoneal sarcomas (RPS) present a surgical challenge with high rates of local recurrence (LR). We investigated the role of intraoperative electron radiotherapy (IOeRT) in reducing LR after surgical resection of RPS., Methods: A retrospective analysis of all patients who underwent surgical resection for RPS between 2014 and 2021 at a tertiary academic referral center (n = 172). Patients included underwent surgical resection of their RPS and received IOeRT (n = 36) and were compared by case control matching to patients with similar tumor characteristics (recurrence status and tumor grade) that did not receive IOeRT (n = 36)., Results: The median length of hospitalization was 8 days (range, 4-34) in the IOeRT group and 10 days (range, 2-42) in the non-IOeRT group (p = 0.25). The mean operating room (OR) time was 4h (±1.3) and 4h (±1.9) in the IOeRT and non-IOeRT groups respectively, (p = 0.37). Complete resection with R0 margins was achieved in 30 patients (83.3%) and 24 patients (66.6%) in the IOeRT and non-IOeRT groups, respectively (p = 0.1). R1 resection was achieved in 6 patients (16.6%) and 12 patients (33.3%) respectively, (p = 0.1). The resected organ weighted score was significantly different between the groups; score 0 observed in 19 (52.7%) patients in the IOeRT group and 3 (8.3%) in the non-IOeRT group (p < 0.001), score 1 observed in 7 (19.4%) in the IOeRT group and 17 (47.2%) in the non-IOeRT group (p = 0.012). The rate of severe complications (CD score>3) did not differ between the groups, 5 (13.8%) patients in the IOeRT group and 9 (25%) patients in the non-IOeRT group (p = 0.23). No radiation associated complications were noted. The 2-year local recurrence free survival (LRFS) was 75.9% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.4). The 2-year IOeRT field recurrent free survival (IRFS) was 88.4% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.04)., Conclusions: The use of IOeRT did not increase the rate of surgical complications and was associated with superior local control in the radiation field, improved organ preservation without an impact on overall survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: One of the most common ileostomy-related complications is high output stoma (HOS) which causes significant fluids and electrolytes disturbances. We aimed to analyze the incidence, severity, and risk factors for readmission for HOS., Methods: We reviewed all patients who underwent loop ileostomy closure in a single institution between 2010 and 2020. Patients that were readmitted for dehydration due to HOS during the time interval between the creation and the closure of the stoma were identified and divided into a study (HOS) group. The remaining patients constructed the control group., Results: A total of 307 patients were included in this study, out of which, 41 patients were readmitted 73 times (23.7% readmission rate) for the HOS group, and the remaining 266 patients constructed the control group. Multivariate analysis identified; advanced American Society of Anesthesiologists (ASA) physical status (PS) classification, elevated baseline creatinine, and open surgery as risk factors for HOS. Renal function worsened among the entire cohort between the construction of the stoma to its closure (mean creatinine of 0.82 vs. 0.96, P<0.0001)., Conclusion: Loop ileostomy formation is associated with a substantial readmission rate for dehydration as a result of HOS, and increasing the risk for renal impairment during the duration of the diversion. We identified advanced ASA PS classification, open surgery, and elevated baseline creatinine as predictors for HOS.

Introduction: Soft tissue sarcomas (STS) of the pelvis present a surgical and oncological challenge. We investigated the outcomes of patients undergoing resection of pelvic sarcomas., Methods: A retrospective analysis of all patients who underwent surgical resection for STS between 2014 and 2021 at a tertiary academic referral center (n = 172). Included all patients with primary or recurrent STS which originated or extended to the pelvic cavity (n = 29)., Results: The cohort was divided into primary pelvic sarcomas (n = 18) and recurrent pelvic sarcomas (rPS, n = 11). Complete R0/R1 resection was achieved in 26 patients (89.6%). The postoperative complication rate was 48.3%. The rate of major complications was 27.5%. The median time of follow-up from surgery was 12.3 months (range, 0.6-60.3 months). Disease-free survival was superior in the primary pelvic sarcomas group compared to the rPS group (P = 0.002). However, there was no significant difference in overall survival, (P = 0.52). Univariant and multivariant analyses identified rPS group (Hazard Ratio 8.68, P = 0.006) and resection margins (Hazard Ratio 6.29, P = 0.004) to be independently associated with disease-free survival., Conclusions: We have demonstrated that achieving R0/R1 resection is feasible. Oncological outcomes are favorable for primary tumors, whereas recurrent tumors exhibit early recurrences. Consideration of resection of recurrent pelvic STS should involve a careful multidisciplinary evaluation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Constraints of pelvic anatomy render complete cytoreduction (CRS) challenging. The aim of this study is to investigate the impact of pelvic peritonectomy during CRS/HIPEC on colorectal peritoneal metastasis (CRPM) patients' outcomes., Methods: This is a retrospective analysis of a prospectively maintained CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) database. The analysis included 217 patients with CRPM who had a CRS/HIPEC between 2014 and 2021. We compared perioperative and oncological outcomes of patients with pelvic peritonectomy (PP) (n = 63) to no pelvic peritonectomy (non-PP) (n = 154)., Results: No differences in demographics were identified. The peritoneal cancer index (PCI) was higher in the PP group with a median PCI of 12 vs. 6 in the non-PP group (p < 0.001). Operative time was 4.9 vs. 4.3 h in the PP and non-PP groups, respectively (p = 0.63). Median hospitalization was longer in the PP group at 12 vs. 10 days (p = 0.007), and the rate of complications were higher in the PP group at 57.1% vs. 39.6% (p = 0.018). Pelvic peritonectomy was associated with worse disease-free (DFS) and overall survival (OS) with 3-year DFS and OS of 7.3 and 46.3% in the PP group vs. 28.2 and 87.8% in the non-PP group (p = 0.028, p .> 0.001). The univariate OS analysis identified higher PCI (p = 0.05), longer surgery duration (p = 0.02), and pelvic peritonectomy (p < 0.001) with worse OS. Pelvic peritonectomy remained an independent prognostic variable, irrespective of PCI, on the multivariate analysis (p < 0.001)., Conclusions: Pelvic peritonectomy at the time of CRS/HIPEC is associated with higher morbidity and worse oncological outcomes. These findings should be taken into consideration in the management of patients with pelvic involvement., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis., Methods: This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392). We analyzed patients' demographics, operative and perioperative details, SBO re-admission data, and long-term oncological outcomes., Results: Out of 366 patients, 73 (19.9%) were re-admitted with SBO. The cause was adhesive in 42 (57.5%) and malignant (MBO) in 31 (42.5%). The median time to obstruction was 7.7 months (range, 0.5-60.9). Surgical intervention was required in 21/73 (28.7%) patients. Obstruction eventually resolved (spontaneous or by surgical intervention) in 56/73 (76.7%) patients. Univariant analysis identified intraperitoneal chemotherapy agents: mitomycin C (MMC) (HR 3.2, p = 0.003), cisplatin (HR 0.3, p = 0.03), and doxorubicin (HR 0.25, p = 0.018) to be associated with obstruction-free survival (OFS). Postoperative complications such as surgical site infection (SSI), (HR 2.2, p = 0.001) and collection (HR 2.07, p = 0.015) were associated with worse OFS. Multivariate analysis maintained MMC (HR 2.9, p = 0.006), SSI (HR 1.19, p = 0.001), and intra-abdominal collection (HR 2.19, p = 0.009) as independently associated with OFS. While disease-free survival was similar between the groups, overall survival (OS) was better in the non-obstruction group compared with the obstruction group (p = 0.03)., Conclusions: SBO after CRS/HIPEC is common and complex in management. Although conservative management was successful in most patients, surgery was required more frequently in patients with MBO. Patients with SBO demonstrate decreased survival., (© 2022. Society of Surgical Oncology.)

Background: Metastatic spread of malignant melanoma to the abdomen presents a therapeutic challenge. Targeted and Immune-therapies dramatically improve patients' survival, yet some patients may still benefit from surgical intervention. This study investigates the outcomes of surgical treatment of abdominal metastatic melanoma in the era of modern therapy., Methods: This is a retrospective study of all patients who underwent surgical resection for abdominal metastatic melanoma between the years 2009-2021 (n = 80). We examined the clinical, operative, perioperative, and oncological outcomes of these patients., Results: The cohort included a therapeutic group (T, n = 43) and palliative group (P, n = 37). The rate of overall post-operative complications was lower in the T group (n = 3, 9.3%) compared to the P group (n = 10, 27.1%) (p = 0.04), but no difference in major complications rate (p = 0.41). The median follow-up was 13.4 months (range, 0.5-107), with an estimated 2- and 5-years survival of 66.5% and 45.3% respectively. The estimated 2- and 5-years survival of the T group was 76.61% and 69.65%, and 49.01% and 28.01% in the P group (p = 0.005). Univariate analysis identified Therapeutic resection (HR 3.2, p = 0.008), isolated lesions (HR 1.47, p = 0.033) and major complication score (HR 1.8, p=<0.001) to be correlated with survival. On multivariate analysis, Therapeutic resection (HR 2.53, p = 0.042) and major complication score (HR 1.62, p = 0.004) remained significant independent factors correlated with survival. In patients who progressed on treatment, and their progression was treated with surgical resection 46.1% where able to be maintained on the same preoperative treatment strategy., Conclusion: We have demonstrated that abdominal metastesectomy is a safe and oncologically efficacious therapy in selected patients. Especially in the era of modern therapeutics, patients with isolated disease site, limited resectable progression on therapy, or patients with symptomatic metastases should be considered for surgical resection., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Bariatric patients have a high prevalence of hiatal hernia (HH). HH imposes various difficulties in performing laparoscopic bariatric surgery. Preoperative evaluation is generally inaccurate, establishing the need for better preoperative assessment., Objective: To utilize machine learning ability to improve preoperative diagnosis of HH., Methods: Machine learning (ML) prediction models were utilized to predict preoperative HH diagnosis using data from a prospectively maintained database of bariatric procedures performed in a high-volume bariatric surgical center between 2012 and 2015. We utilized three optional ML models to improve preoperative contrast swallow study (SS) prediction, automatic feature selection was performed using patients' features. The prediction efficacy of the models was compared to SS., Results: During the study period, 2482 patients underwent bariatric surgery. All underwent preoperative SS, considered the baseline diagnostic modality, which identified 236 (9.5%) patients with presumed HH. Achieving 38.5% sensitivity and 92.9% specificity. ML models increased sensitivity up to 60.2%, creating three optional models utilizing data and patient selection process for this purpose., Conclusion: Implementing machine learning derived prediction models enabled an increase of up to 1.5 times of the baseline diagnostic sensitivity. By harnessing this ability, we can improve traditional medical diagnosis, increasing the sensitivity of preoperative diagnostic workout.

Aims: This study presents our experience with Intra-Operative Electron Radio-Therapy (IOeRT) using a mobile linear accelerator at the Sheba Medical Center., Background: Intraoperative radiotherapy is an alternative approach of partial breast irradiation for patients with early breast cancer and low risk for local recurrence who are undergoing breast conservation surgery., Methods: Patients were selected by a multidisciplinary team according to ASTRO\GEC-ESTRO guidelines for partial breast irradiation. IOeRT was administered using SIT LIAC HWL®., Results: A total of 28 patients were referred for breast conservation surgery and IOeRT between 8/2019 and 10/2020; 27/28 received IOeRT. In one patient, radiation was aborted due to anaphylactic shock in response to patent blue dye injected for sentinel node identification. Larger than usual seroma were reported on the first post-operative visit in all patients, and regressed spontaneously in 3-6 months. Infected seroma developed post-operatively in 5 patients, requiring surgical drainage in 2 patients. Final pathology matched the preoperative biopsy. There were no cases of pathology upstaging requiring additional adjuvant irradiation or chemotherapy. The patient who did not receive IOeRT was treated with adjuvant external radiotherapy., Conclusions: IOeRT is a safe alternative to partial breast irradiation, with a slight increase of postoperative infection rate.

Introduction: Breast cancer outcome is dependent on disease stage. The aim of the study was to assess the role of PET/CT in the evaluation of axillary lymph node and distant metastases in women with newly diagnosed primary breast cancer., Materials and Methods: We assessed, among patients with newly diagnosed primary breast cancer, associations of [ 18 F] fluorodeoxyglucose (FDG) uptake (maximum standardized uptake value [SUV max ]) with clinical variables of the primary tumor, including regional nodal status and the presence of distant metastases., Results: Of 324 patients, 265 (81.8%) had focal uptake of FDG that corresponded with the cancerous lesion, and 21 (6.5%) had no FDG-avid findings. The remaining 38 patients had diffuse or nonspecific uptake of FDG. Among patients with a focal uptake of FDG (n = 265), the mean tumor size was 2.6 ± 1.9 (range 0.5-13.5), and the mean SUV max was 5.3 ± 4.9 (range 1.2-25.0). In 83 patients (25.6%), PET/CT demonstrated additional suspected foci in the same breast. FDG-avid lymphadenopathy was observed in 156 patients (48.1%). Further assessment of lymph node involvement was available for 55/156 patients (axillary lymph node dissection [n = 21]; core needle biopsy [n = 34]) and confirmed axillary lymph node metastases in 47 (85.5%)). Thirteen patients (4.0%) had FDG-avid supraclavicular lymph nodes and six (1.9%) had FDG-avid internal mammary lymph nodes. Distant FDG-avid lesions were detected in 33 patients (10.2%)., Conclusion: PET/CT is a useful diagnostic tool for staging breast cancer patients, but its use should be limited to specific clinical situations; further evaluation is needed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Female BRCA1/BRCA2 mutation carriers may elect bilateral risk-reducing mastectomy. There is a paucity of data on yield of imaging surveillance after risk-reducing mastectomy. This retrospective study focused on female BRCA1/BRCA2 mutation carriers who underwent bilateral mastectomy either as primary preventative, or as secondary preventative, after breast cancer diagnosis. All participants underwent breast imaging at 6- to 12-month intervals after mastectomy. Data on subsequent breast cancer diagnosis and timing were collected and compared between the groups. Overall, 184 female mutation carriers (134 BRCA1, 45 BRCA2, 5 both BRCA genes) underwent bilateral mastectomy after initial breast cancer diagnosis, between April 1, 2009 and August 31, 2018. During a mean follow-up of 6.2 ± 4.2 years, 13 (7.06%) were diagnosed with breast cancer; 12 ipsilateral (range: 0.4-28.8 years) and 1 contralateral breast cancer, 15.9 years after surgery. On the contrary, among asymptomatic BRCA1 (n = 40) and BRCA2 (n = 13) mutation carriers who underwent primary risk-reducing mastectomy (mean age at surgery 39.5 ± 8.4 years); none has developed breast cancer after a mean follow-up of 5.4 ± 3.4 years. BRCA1/BRCA2 mutation carriers with prior disease who underwent risk-reducing mastectomy after breast cancer diagnosis are still prone for developing ipsi or contralateral breast cancer, and therefore may benefit from continues clinical and imaging surveillance, unlike BRCA1/BRCA2 mutation carriers who undergo primary preventative bilateral mastectomy., (© 2021 Wiley Periodicals LLC.)

Introduction: In primary Crohn's disease (CD), laparoscopic ileocolic resection has been shown to be both feasible and safe, and is associated with improved outcomes in terms of postoperative morbidity and length of hospital stay. However, it is unclear whether the laparoscopic approach can be routinely proposed as a safe procedure for patients with complex enterovisceral fistulas.The aim of this study is to assess the feasibility and safety of laparoscopic surgery for complex enterovisceral fistulas, and compare it with CD patients who underwent primary laparoscopic ileocolic resection., Patients and Methods: All patients who underwent laparoscopic primary ileocolic resection (LICR) for complex enterovisceral fistulas between July 2006 and July 2017 were included. They were compared with all consecutive patients who underwent LICR for nonfistulizing CD in the same period of time. Patients with previous bowel resections or recurrent disease were excluded., Results: Nineteen patients with 20 enterovisceral fistulas (group I) were compared with 61 patients who underwent LICR for nonfistulizing disease (group II). There were no differences between the groups in age, sex, preoperative body mass index, nutritional status, and American Society of Anesthesiology score. There was no conversion to open surgery in both groups.There were no significant differences between groups in terms of operative time [120 (range: 65 to 232) vs. 117 (range: 62 to 217) min, P=0.7], hospital stay [6 (5 to 8) vs. 7 (5 to 65) days, P=0.56], overall morbidity 26.3% versus 16.4% (P=0.33), major morbidity (Clavien-Dindo >3) 15.7% versus 10% (P=0.66) and reoperation rates 5.3% versus 4.9% (P=0.9). There was no mortality in both groups., Conclusions: Our experience shows that the laparoscopic approach for complex enterovisceral fistulas in selected CD patients is both feasible and safe in the hands of experienced inflammatory bowel disease surgeons with extensive expertise in laparoscopic surgery. Larger study cohorts are needed to confirm these findings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Rectal cancer surgery is continuously evolving. Transanal total mesorectal excision (TaTME) is a relatively new surgical approach with possible advantages in comparison to current standard surgical techniques. Several studies in recent years have validated this approach regarding safety and effectiveness. We describe our initial experience with TaTME evaluating surgical parameters, post-operative outcomes and short-term oncological outcomes., Methods: This is a retrospective study reviewing all patients who underwent TaTME in a single institution from May 2015 to April 2018., Results: The cohort included 25 patients with an average age of 60.4 (range: 40-86), of which 13 (52%) patients were male. The average body mass index was 26.1. The overall 30-day morbidity rate was 40%, with 20% (five cases) being severe complications, defined by Clavien-Dindo Grade of 3b or above. There were three major interoperative complications. Four cases (16%) required reoperation during the first 30 post-operative days. The median length of stay was 8 days. The surgery duration was on average 296 min (range: 205-510). Negative resection margins were achieved in all patients. At a median follow-up period of 14 months, there were no local recurrences, and 4 cases (16%) had a distant recurrence., Conclusion: This study describes our initial experience with TaTME, which requires a substantial learning curve to minimise complications and morbidity. Oncological outcomes as expressed by the resection margins, number of lymph nodes harvested and local recurrence rates were all comparable to previously published data., Competing Interests: None

Background: The rate of risk-reducing bilateral mastectomy (RRBM) among cancer-free Israeli female BRCA1/BRCA2 mutation carriers was reportedly 13% in 2010. Current RRBM rates in Israel and factors seemingly associated with opting for RRBM were reevaluated., Methods: Israeli female cancer-free BRCA1/BRCA2 mutation carriers, who were followed at the high-risk clinic at Sheba Medical Center between January 2011 and April 2020 were eligible. Univariate Cox regression and log-rank test were used to study the crude association between potential predictors and performance of RRBM., Results: Overall, 427 cancer-free BRCA1 (n = 218) or BRCA2 (n = 209) mutation carriers were included. Median age at genotyping was 33.6 years (interquartile range 26.8-41.8 years), median follow-up 4.4 years (range 0.1-7.6 years). Overall, 41/427 (9.6%) participants underwent RRBM, all of them within 5 years of genotyping. Being married (HR-2.57, p = 0.017) and having a first degree relative with breast cancer (BC) (HR-2.19, p = 0.017) were positively associated with RRBM, whereas any previous benign breast biopsy was negatively associated (HR-0.48, p = 0.029) with performing RRBM., Conclusions: RRBM is still infrequently elected by Israeli BRCA1/BRCA2 mutation carriers, with married women with one relative with BC who have not undergone previous breast biopsy more likely to opt for RRBM.

Background: Advanced breast cancer (ABC) at diagnosis carries a worse prognosis, and can be attributed to delay in diagnosis, failure of screening tests, or aggressive biology. Better understanding of factors related with ABC at diagnosis could help decrease the proportion of such cases. Patients and Methods: This is a retrospective study of all patients diagnosed and treated for breast cancer (BC) at a single institution between 2012 and 2015. Data were collected from medical records and phone interviews, and included demographic, clinical, and tumor-related data, and adherence to screening recommendations. Results: Of 555 newly diagnosed BC patients, 390 (70.3%) were diagnosed early (stage 0-IIa), and 165 (29.7%) were diagnosed with ABC (stage IIb-IV). Of the165 patients diagnosed with ABC, 57 (34.5%) underwent screening mammography as recommended. More patients with ABC were <50 years (29.1% vs. 19%, p  = 0.006). ABC was associated with higher grade, higher proliferation rate, Her2/neu overexpression, luminal B-like, and triple negative phenotypes. Mammography within 30 months of diagnosis was more prevalent among those diagnosed early (64.6% vs. 34.5%, p  = 0.003). Only 31 (18.8%) of the screening eligible patients who were diagnosed at advanced stage did not adhere to screening recommendations. Conclusions: ABC at diagnosis is related to aggressive tumor biology and age <50 years. It is also associated with lower adherence to screening mammography; however, more than one third of patients diagnosed with ABC who were eligible for screening underwent screening mammography as recommended. Further research is needed to elucidate factors related with ABC at diagnosis, review screening guidelines, and develop more effective screening modalities., Competing Interests: No competing financial interests exist., (© Orli Friedman-Eldar et al. 2020; Published by Mary Ann Liebert, Inc.)

Background: Minimally invasive adrenalectomy has facilitated resection of resistant adrenal metastases. The adrenal gland may function as a sanctuary site for metastatic growth despite systemic therapy. The objective of the study was to assess the outcomes of selective minimally invasive adrenalectomy during immunotherapy., Methods: Candidates included patients with adrenal metastases resistant to systemic therapy who underwent minimally invasive adrenalectomy., Results: There were 15 patients undergoing 16 minimally invasive adrenalectomies. Patients received either immunotherapy or BRAF inhibition prior to surgery. The mean operative time was 130 min with a median length of hospital stay of 2 days. At a median follow up of 24 months, 7 patients have no evidence of disease, 6 patients had progression with eventual mortality, while another patients has stable disease with maintenance therapy. One was lost to follow up., Conclusion: Despite an increase in objective durable responses in metastatic melanoma, there is still some site-specific resistance in isolated areas like the adrenal where early minimally invasive adrenalectomy remains indicated., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest with any of the data submitted in this manuscript., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Silastic ring vertical gastroplasty (SRVG) was a popular restrictive procedure 2 and 3 decades ago. However, it was associated with severe complications and a high rate of reoperation due to failure. Examination of long-term outcomes of those patients that underwent SVRG is limited. The aim of our study was to determine the long-term outcomes (over 13 years) of SRVG in our institution and to review the literature of long-term outcomes following SVRG., Methods: Following IRB approval, we reviewed patients who underwent SRVG between 1996 and 2001. Weight loss parameters, preoperative comorbidities, were compared to the follow-up data., Results: In total, 92 patients underwent SRVG, and 89 met the inclusion criteria. Mean age was 52.4 ± 10.6 years and body mass index (BMI) was 46.1 ± 6.5 Kg/m 2 . Preoperative comorbidities rate included diabetes mellitus (19.1%), hypertension (32.5%), hyperlipidemia (21.3%), joints disease (6.7%), mood disorders (7.8%), and dyspeptic disorders (3.3%). Mean length of follow-up was 208.5 ± 16.8 months. Thirty-eight patients (43%) had to be reoperated due to complications and 24 (30%) had an additional bariatric surgery. Follow-up BMI was 34.2 ± 9.8 Kg/m 2 (p < 0.001). There was no improvement in any of the comorbidities; incidence of joint disease and dyspeptic disorders were significantly higher at the follow-up (p = 0.03, p < 0.001, respectively)., Conclusions: SRVG procedure was associated with high rates of reoperations and revisions. The majority of our patients showed poor resolution of comorbidities and even worsening of some. Our data confirms that SRVG is not suitable as a bariatric procedure.

Background: Annual MRI screening is associated with a significant reduction in advanced-stage breast cancer diagnosis in BRCA1/2 mutation carriers. The impact that early detection has on subsequent oncological treatment is less frequently reported. In this study we compared disease stage and therapeutic approaches in BRCA1/2 mutation carriers who developed breast cancer while adhering to the recommended surveillance scheme ("known carriers"), with women who became aware of their BRCA mutation status after breast cancer diagnosis ("latent carriers")., Methods: Data on tumor characteristics, disease stage, and therapeutic decisions were collected on BRCA1/2 mutation carriers treated for breast cancer at the Chaim Sheba Medical Center., Results: Data were available for 298 BRCA1/2 carriers. Median follow-up was 77.4 months (range, 3.5-520). Age at diagnosis was not statistically different between known carriers (n = 96; median age at diagnosis 44.7 years) and latent carriers (n = 202; 43.7 years); p = 0.8284. Of known carriers, 19.8% were diagnosed with carcinoma in situ vs. 5% of latent carriers (p = 0.0012). Stage T1N0 disease was diagnosed in 54/96 (56.3%) of known carriers vs. 59/202 (29.2%) of latent carriers (p < 0.00001). Neoadjuvant or adjuvant chemotherapy was administered to 46/96 (47.9%) of known carriers compared with 162/202 (80.2%) of latent carriers (p < 0.00001)., Conclusions: While early stage breast cancer was diagnosed frequently among known BRCA1/2 carriers under tight surveillance, almost half of these women were treated with chemotherapy. Healthy BRCA1/2 mutation carriers should be informed about these rates while discussing risk-reducing surgical options., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background/aim: Adoptive transfer of tumor-infiltrating lymphocytes (TILs) combined with non-myeloablative chemotherapy (NMA) has been shown to prolong survival in patients with metastatic disease., Materials and Methods: Tissue harvesting was performed form a variety of sites. TILs were isolated, expanded and infused with bolus high-dose IL-2., Results: Between 2008 and 2018, 242 lesions were resected for TILs harvesting from a range of sites form 196 patients without mortality and with minimal morbidity. Of those harvested, 75 were unable to complete therapy because of clinical deterioration during the wait period. Of 121 evaluable treated patients, there was no effect of metastatic site biopsied on the mean fold TIL expansion. Those receiving prior ipilimumab had a higher TIL fold expansion but a lower TIL fold expansion than those exposed to anti-PD1 therapy., Conclusion: Harvesting may be safely performed with successful TIL expansion from most sites. Prior check point inhibitory immunotherapy may potentially influence TIL fold expansion., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: The best local management for breast cancer recurrence following conservative treatment for breast cancer (BC) continues to be an open question. In this study, we compared patients' outcome after salvage lumpectomy (SL) vs mastectomy for ipsilateral breast tumor recurrence (IBTR)., Materials and Methods: Between 1987 and 2014 we identified 121 patients with pT0-2, N0-3, M0 BC who had BCT as their primary treatment, and subsequently had IBTR (unifocal). 47 patients underwent SL and 74 salvage mastectomy (SM) as the local treatment for their 1st recurrence., Results: Median follow-up was 14 years (1-30) from first BC diagnosis. For the SL and SM cohorts, 8 and 10 patients (17%, 13.5%, P = 0.22), respectively, developed subsequent local recurrence as a 3rd event. Although in MVA, woman who underwent SL had higher chances of having a 2nd recurrence (3rd event), P = 0.020, at a median follow-up of 14 years, 95.8% of SL patients are alive, NED, 85% are mastectomy free. 87% of patients who opted for SM are alive, NED. Having re-irradiation following SL did not protect against 2nd breast cancer recurrence (3rd event, P = 0.42)., Conclusion: Salvage lumpectomy following IBTR, while associated with higher second LR rate than SM is not associated with inferior outcome. With survival >95% at 14 years in the SL cohort, salvage lumpectomy with or without re-radiation, in a selected population (unifocal T), represents an acceptable treatment option for patients in order to delay time to mastectomy without reducing BC survival. Both options should be discussed prior to any surgical decision., (© 2019 Wiley Periodicals, Inc.)

The treatment of peritoneal surface malignancies, either primary or secondary (peritoneal metastasis), has evolved over the past two decades. A nihilistic approach of incurable "carcinomatosis" is changing into treatment of peritoneal metastasis with curative intent. The aim of the present study is to review the current practice, past history, and future of peritoneal surface oncology in Israel. A systematic review of all patients treated in institutions performing cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies. Each center provided the following data: start year, number of total cases, number of cases performed in 2017, and the method used (open vs. closed technique). Between 1990 and 2018, there were 1462 patients treated by CRS/HIPEC in Israel by eight different surgical groups in six medical centers. Currently, there are seven surgical groups in six medical centers routinely performing CRS/HIPEC. The annual rate of CRS/HIPEC was 171 cases in 2017 with a range of (4-69 cases/center). This is the first step of establishing an Israeli Peritoneal Surface Oncology Group that will have joined database and perform clinical trials in this challenging field of surgical oncology.

The techniques of portal vein embolization (PVE) or ligation (PVL) have the goals of combining an induced atrophy of metastatic segments with the rapid relative compensatory hypertrophy of the postresection future liver remnant (FLR). Our study examines the anatomy of right-left hepatic lobar venous connections in the adult cadaver using corrosion cast analysis in an effort to define some of the inherent anatomical reasons why both PVL and PVE may be technically unsuccessful. Corrosion cast models of 215 cadaveric liver specimens were evaluated for hepatopetal venous blood flow, with a particular emphasis on cholecystic venous drainage patterns, including 57 cases prepared after lobar portal venous ligation. In 88.8 per cent of corrosion casts, there was a segmental venous communication between the gallbladder and all segments of the liver, except segment II. There was cystic vein drainage directly into a main lobar branch or directly into the portal vein itself in 11.2 per cent of cases. In all 57 cases, after portal lobar venous division, in situ cystic veins allowed persistent venous communication between lobes. Our cadaveric corrosion cast study has suggested that there is extensive intrahepatic cholecystic venous drainage to many segments of the liver. Perfusion from the gallbladder may potentially contribute to a limited response to procedures which interrupt the portal venous flow and could affect their capacity to induce an adequate FLR which would permit a wider hepatectomy.

Background and Objective: Entero vesical fistulas (EVFs) are an uncommon complication mainly of diverticular disease (70%) and less commonly of Crohn's disease (10%). Only about 10% are caused by malignancies. At this time, it is unclear whether the laparoscopic approach can be routinely proposed as a safe procedure for patients with EVF. The aim of this study was to assess the feasibility and safety of laparoscopic surgery in the treatment of EVFs in patients with complicated diverticular and Crohn's disease., Methods: All patients with the diagnosis of EVF who underwent laparoscopic surgery were identified from prospective collected data based in two institutions between 2007 and 2017. Patients with malignancy were excluded. Recorded parameters included operative time, conversion to open surgery, the presence of a protective loop ileostomy, perioperative complications, number of units of blood transfused, postoperative course, and histologic findings., Results: Seventeen patients were included in the study: 10 patients with a colo-vesical fistula due to diverticular disease, and 7 patients with an ileo-vesical fistula due to Crohn's disease. There were no conversions to open surgery and none of the patients needed a protective ileostomy. The bladder was sutured in 12 patients (70%). No intra-operative complications were met, and no blood transfusions were needed; there were no anastomotic leaks, nor mortality in both groups., Conclusions: The laparoscopic approach for benign EVF in selected patients is both feasible and safe in the hands of experienced surgeons with extensive expertise in laparoscopic surgery., Competing Interests: Conflicts of Interest: All authors declare no conflict of interest regarding the publication of this article.