CCAT1 lncRNA is chromatin-retained and post-transcriptionally spliced.

Super-enhancers are unique gene expression regulators widely involved in cancer development. Spread over large DNA segments, they tend to be found next to oncogenes. The super-enhancer c-MYC locus forms long-range chromatin looping with nearby genes, which brings the enhancer and the genes into proximity, to promote gene activation. The colon cancer-associated transcript 1 (CCAT1) gene, which is part of the MYC locus, transcribes a lncRNA that is overexpressed in colon cancer cells through activation by MYC. Comparing different types of cancer cell lines using RNA fluorescence in situ hybridization (RNA FISH), we detected very prominent CCAT1 expression in HeLa cells, observed as several large CCAT1 nuclear foci. We found that dozens of CCAT1 transcripts accumulate on the gene locus, in addition to active transcription occurring from the gene. The accumulating transcripts are released from the chromatin during cell division. Examination of CCAT1 lncRNA expression patterns on the single-RNA level showed that unspliced CCAT1 transcripts are released from the gene into the nucleoplasm. Most of these unspliced transcripts were observed in proximity to the active gene but were not associated with nuclear speckles in which unspliced RNAs usually accumulate. At larger distances from the gene, the CCAT1 transcripts appeared spliced, implying that most CCAT1 transcripts undergo post-transcriptional splicing in the zone of the active gene. Finally, we show that unspliced CCAT1 transcripts can be detected in the cytoplasm during splicing inhibition, which suggests that there are several CCAT1 variants, spliced and unspliced, that the cell can recognize as suitable for export.

Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BACKGROUND: Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC. METHODS: We performed a retrospective analysis of our prospectively maintained CRS/HIPEC database and evaluated all patients with CRC peritoneal metastases between 2012 and 2022. We divided the cohorts between those with low operative PCI (PCI<20) and high operative PCI (PCI =>20). We examined demographic, clinicopathologic data, perioperative, and oncological outcomes between the cohorts. RESULTS: Of the 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI <20 and 43 with PCI => 20. Median radiologic preoperative and operative PCI was 4 and 10 versus 7 and 24.5 in the low and high PCI cohorts, respectively. Operative time was longer (6 vs. 4 h) and blood loss higher (500 vs. 400 mL) in the high PCI cohort. All other demographic, clinicopathological, and operative characteristics were similar. Median disease free survival (DFS) was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months), (p = 0.001 and p = 0.189, respectively), comparatively with an only chemotherapy strategy. CONCLUSIONS: Appropriately selected patients with CRC metastases and extremely high PCI demonstrate similar perioperative safety outcomes in experienced tertiary referral centers. Despite a shorter median DFS, these carefully selected patients demonstrated similar median OS.

Distinct breast cancer phenotypes in BRCA 1/2 carriers based on ER status.

PURPOSE: BRCA1/2 genes are the two main genes associated with hereditary breast cancers (BC). In the present study, we explore clinical and molecular characteristics of BRCA-associated BC in relation to estrogen receptor (ER) status. METHODS: Three BC databases (DB) were evaluated: (i) Hadassah oncogenetics (n = 4826); (ii) METABRIC (n = 1980), and (iii) Nick-Zainal (n = 560). We evaluated age at diagnosis in BRCA positive (BP) and BRCA negative (BN) patients, and tested for mutational signature differences in cohort iii. mRNA differential expression analysis (DEA) and pathway analysis were performed in cohort ii. RESULTS: Age at diagnosis was lower in BP vs. BN tumors in all cohorts in the ER- group, and only in cohort i for the ER + group. Signature 3 was universal in BP BC, whereas several signatures were associated with ER status. Pathway analysis was performed between BP&BN, and was significant only in ER- tumors: the major activated pathways involved cancer-related processes and were highly significant. The most significant pathway was estrogen-mediated S-phase entry and the most activated upstream regulator was ERBB2. CONCLUSION: Signature 3 was universal for all BP BC, while other signatures were associated with ER status. ER + BP& BN show similar genomic characteristics, ER- BP differed markedly from BN. This suggests that the initial carcinogenic process is universal for all BRCA carriers, but further insults lead to the development of two genomically distinct subtypes ER- and ER + . This may shed light on possible mechanisms involved in BP and carry preventive and therapeutic implications.

Resection of Recurrent Pelvic Soft Tissue Sarcoma: Is the Risk Worth the Reward?

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.

Natural History and Management of Small-Bowel Obstruction in Patients After Cytoreductive Surgery and Intraperitoneal Chemotherapy.

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.

Long-term Outcomes of Minimally Invasive Versus Open Abdominoperineal Resection for Rectal Cancer: A Single Specialized Center Experience.

BACKGROUND: Randomized studies have validated laparoscopic proctectomy for the treatment of rectal cancer as noninferior to an open proctectomy, but most of those studies have included sphincter-preserving resections along with abdominoperineal resection. OBJECTIVE: This study aimed to compare perioperative and long-term oncological outcomes between minimally invasive and open abdominoperineal resection. DESIGN: This study is a retrospective analysis of a prospectively maintained database. SETTINGS: The study was conducted in a single specialized colorectal surgery department. PATIENTS: All patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2016 were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the perioperative and long-term oncological outcomes. RESULTS: We included 452 patients, 372 in the open group and 80 in the minimally invasive group, with a median follow-up time of 74 months. There were significant differences between the groups in terms of neoadjuvant radiation treatment (67.5% of the open versus 81.3% of the minimally invasive group, p = 0.01), operative time (mean of 200 minutes versus 287 minutes, p < 0.0001), and mean length of stay (9.5 days versus 6.6 days, p < 0.0001). Overall complication rates were similar between the groups (34.5% versus 27.5%, p = 0.177). There were no significant differences in the mean number of lymph nodes harvested (21.7 versus 22.2 nodes, p = 0.7), circumferential radial margins (1.48 cm versus 1.37 cm, p = 0.4), or in the rate of involved radial margins (10.8% versus 6.3%, p = 0.37). Five-year overall survival was 70% in the open group versus 80% in the minimally invasive group (p = 0.344), whereas the 5-year disease-free survival rate in the open group was 63.2% versus 77.6% in the minimally invasive group (p = 0.09). LIMITATIONS: This study was limited because it describes a single referral institution experience. CONCLUSIONS: Although both approaches have similar perioperative outcomes, the minimally invasive approach benefits the patients with a shorter length of stay and a lower risk for surgical wound infections. Both approaches yield similar oncological technical quality in terms of the lymph nodes harvested and margins status, and they have comparable long-term oncological outcomes. See Video Abstract at http://links.lww.com/DCR/B754.RESULTADOS A LARGO PLAZO DE LA RESECCIÓN ABDOMINOPERINEAL MÍNIMAMENTE INVASIVA VERSUS ABIERTA PARA EL CÁNCER DE RECTO: EXPERIENCIA DE UN SOLO CENTRO ESPECIALIZADOANTECEDENTES:Estudios aleatorizados han validado la proctectomía laparoscópica para el tratamiento del cáncer de recto igual a la proctectomía abierta, pero la mayoría de esos estudios han incluido resecciones con preservación del esfínter junto con resección abdominoperineal.OBJETIVO:Comparar los resultados oncológicos perioperatorios y a largo plazo entre la resección abdominoperineal abierta y mínimamente invasiva.DISEÑO:Análisis retrospectivo de una base de datos mantenida de forma prospectiva.ENTORNO CLINICO:Servicio único especializado en cirugía colorrectal.PACIENTES:Todos los pacientes que se sometieron a resección abdominoperineal por cáncer de recto primario entre 2000 y 2016.PRINCIPALES MEDIDAS DE VALORACION:Resultados oncológicos perioperatorios y a largo plazo.RESULTADOS:Se incluyeron 452 pacientes, 372 en el grupo abierto y 80 en el grupo mínimamente invasivo, con una mediana de seguimiento de 74 meses. Hubo diferencias significativas entre los grupos en términos de tratamiento con radiación neoadyuvante (67,5% del grupo abierto versus 81,3% del grupo mínimamente invasivo, p = 0,01), tiempo operatorio (media de 200 minutos versus 287 minutos, p < 0,0001) y la duración media de la estancia (9,5 días frente a 6,6 días, p < 0,0001). Las tasas generales de complicaciones fueron similares entre los grupos (34,5% versus 27,5%, p = 0,177). No hubo diferencias significativas en el número medio de ganglios linfáticos extraídos (21,7 versus 22,2 ganglios, p = 0,7), márgenes radiales circunferenciales (1,48 cm y 1,37 cm, p = 0,4), ni en la tasa de márgenes radiales afectados (10,8 cm). % versus 6,3%, p = 0,37). La supervivencia general a 5 años fue del 70% en el grupo abierto frente al 80% en el grupo mínimamente invasivo (p = 0,344), mientras que la tasa de supervivencia libre de enfermedad a 5 años en el grupo abierto fue del 63,2% frente al 77,6% en el grupo mínimamente invasivo (p = 0,09).LIMITACIONES:Experiencia en una institución de referencia única.CONCLUSIONES:Si bien ambos tienen resultados perioperatorios similares, el enfoque mínimamente invasivo, beneficia a los pacientes con estadía más corta y menor riesgo de infecciones de la herida quirúrgica. Ambos enfoques, producen una calidad técnica oncológica similar en términos de ganglios linfáticos extraídos y estado de los márgenes, y tienen resultados oncológicos comparables a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B754. (Traducción - Dr. Fidel Ruiz Healy).

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Elderly is Safe and Effective.

INTRODUCTION: An increasing proportion of elderly patients (EP) are undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC). They have increased comorbidities and perioperative risk. Current literature is deficient in describing the outcomes of EP undergoing CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of our prospectively maintained CRS/HIPEC database analyzed perioperative and oncological outcomes of EP (>70 y) compared to younger patients (YP) (<60 y). RESULTS: Of 500 CRS/HIPEC patients, 62 EP and 210 YP were included. Median age was 73 y in EP and 46 y in YP. Demographic, clinical, operative, and perioperative outcomes were similar between groups. American Society of Anesthesiologists > 3 was more prevalent in the EP with 88.2% versus 54.8% in the YP (P < 0.001). Comorbidities were higher in the EP with 87.1% versus 39.0% in the YP (P < 0.001). Peritoneal Cancer Index score was similar with a median of 9. All postoperative and severe complications were similar with 55.2% and 17.1% in the YP and 64.5% and 21.0% in the EP (P = 0.242; P = 0.448). Postoperative mortality was similar with 1.5% in the YP and 5.0% in the EP (P = 0.134). In colorectal primary patients, median overall and disease-free survival was 61.8 and 12.9 mo in the YP and 64.6 and 11.3 mo in the EP (P = 0.363; P = 0.845). CONCLUSIONS: Despite a significant age difference, increased comorbidities, worse American Society of Anesthesiologists, and similar Peritoneal Cancer Index burden, we found no significant differences in perioperative complications or oncological benefit in elderly CRS/HIPEC patients. EP appear to have similar perioperative and oncological outcomes as YP.

Canady Cold Helios Plasma Reduces Soft Tissue Sarcoma Viability by Inhibiting Proliferation, Disrupting Cell Cycle, and Inducing Apoptosis: A Preliminary Report.

Soft tissue sarcomas (STS) are a rare and highly heterogeneous group of solid tumors, originating from various types of connective tissue. Complete removal of STS by surgery is challenging due to the anatomical location of the tumor, which results in tumor recurrence. Additionally, current polychemotherapeutic regimens are highly toxic with no rational survival benefit. Cold atmospheric plasma (CAP) is a novel technology that has demonstrated immense cancer therapeutic potential. Canady Cold Helios Plasma (CHCP) is a device that sprays CAP along the surgical margins to eradicate residual cancer cells after tumor resection. This preliminary study was conducted in vitro prior to in vivo testing in a humanitarian compassionate use case study and an FDA-approved phase 1 clinical trial (IDE G190165). In this study, the authors evaluate the efficacy of CHCP across multiple STS cell lines. CHCP treatment reduced the viability of four different STS cell lines (i.e., fibrosarcoma, synovial sarcoma, rhabdomyosarcoma, and liposarcoma) in a dose-dependent manner by inhibiting proliferation, disrupting cell cycle, and inducing apoptosis-like cell death.

[INTRAOPERATIVE RADIOTHERAPY FOR EARLY BREAST CANCER - THE SHEBA EXPERIENCE AND EARLY OUTCOMES].

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.

Repeat Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Cancer Peritoneal Recurrences is Safe and Efficacious.

BACKGROUND: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) for colorectal cancer peritoneal metastases (CRPM) is associated with improved survival in patients with historically dismal prognosis. Nonetheless, peritoneal recurrences remain common and represent a difficult challenge in these patients' management. Repeat CRS/HIPEC is associated with even greater morbidity and its survival benefit has not yet been clearly demonstrated. METHODS: We retrospectively reviewed our prospectively maintained database and aimed to assess the safety and oncological efficacy of repeat CRS/HIPEC. RESULTS: Two hundred thirty-two patients underwent an initial CRS/HIPEC, whereas 30 subsequently had repeat CRS/HIPEC for CRPM. Groups were similar in demographics, comorbidities, and peritoneal cancer index (PCI). No significant difference in morbidity, hospital stay, or reoperation rate was noted between initial and repeat procedures. Patients who underwent repeat CRS/HIPEC had a median overall survival of 68 months versus 51 months in patients who did not undergo repeat procedure for their peritoneal recurrence (p = 0.03). Disease-free survival (DFS) in patients after repeat and after initial procedure were similar with median of 9.6 versus 12 months, respectively (p = 0.083). Univariate analysis demonstrated that PCI, DFS, and repeat procedure displayed significant factors on outcomes in patients with peritoneal recurrences, whereas PCI > 16 and DFS remained independent predictors on multivariable analysis. CONCLUSIONS: Our analysis, which represents the largest series to date of repeat CRS/HIPEC for CRPM, indicates that this approach as a part of multimodal therapy is both safe and efficacious in appropriately selected patients.

Perioperative and Oncological Outcomes of Combined Hepatectomy with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND: Synchronous peritoneal and liver metastasis in colorectal cancer is a relative contraindication for curative surgery. We aimed to evaluate the safety and oncological outcomes of combined treatment of peritoneal and liver metastasis. METHODS: We conducted a retrospective analysis of metastatic colorectal cancer patients from two prospective databases: peritoneal surface malignancy (n = 536) and hepatobiliary (n = 286). We compared 60 patients treated with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) and hepatectomy; 80 patients treated with cytoreduction and HIPEC only; and 63 patients treated with hepatectomy alone. RESULTS: No differences in demographics were observed between the groups. Median hospital and intensive care unit (ICU) stay was shorter in group C (7 and 1 days, respectively) versus groups A and B (13 and 1 days, and 12 and 1 days, respectively; p < 0.001). Postoperative complications were not significantly different. Median follow-up was 18.6, 23.1, and 30.6 months for groups A, B, and C, respectively. Estimated 5-year overall survival (OS) was 48.8% (group A), 55.4% (group B), and 60.2% (group C) [p = 0.043 for group A vs. group C], and estimated 5-year disease-free survival (DFS) was 14.2% (group A), 23.0% (group B), and 18.6% (group C). Five-year OS was superior in group C compared with group A (p = 0.043), and DFS was superior in group C compared with groups A and B (p = 0.043 and 0.03, respectively). The peritoneum was the site of first recurrence in groups A and B (23.3% and 32.5%, respectively), and the liver was the site of first recurrence in group C (44.4%). CONCLUSIONS: We report favorable perioperative and oncological outcomes in combined cytoreduction/HIPEC and hepatectomy for patients with peritoneal and liver metastasis. Surgical intervention after multidisciplinary discussion should be considered in patients with both peritoneal and hepatic lesions when complete cytoreduction is feasible.

Ratio of Pathological Response to Preoperative Chemotherapy in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer Correlates with Survival.

BACKGROUND: Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response; Group B, high response ratio, and Group C, low response ratio. RESULTS: The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio; the estimated median disease-free survival of Group C was 9.1 months (5.97-12.23), 14.9 months (4.72-25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69-43.31), and was not reached in Groups A and B (p = 0.001). CONCLUSIONS: The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.

Colorectal Surgery Surveillance: A Novel Method for Composing an Automated Real-time Prospective Registry.

BACKGROUND: Medical registries have been shown to be an effective way to improve patient care and reduce costs. Constructing such registries entails extraneous effort of either reviewing medical charts or creating tailored case report forms (CRF). While documentation has shifted from handwritten notes into electronic medical records (EMRs), the majority of information is logged as free text, which is difficult to extract. OBJECTIVES: To construct a tool within the EMR to document patient-related data as codified variables to automatically create a prospective database for all patients undergoing colorectal surgery. METHODS: The hospital's EMR was re-designed to include codified variables within the operative report and patient notes that documented pre-operative history, operative details, postoperative complications, and pathology reports. The EMR was programmed to capture all existing data of interest with manual completion of un-coded variables. RESULTS: During a 6-month pilot study, 130 patients underwent colorectal surgery. Of these, 104 (80%) were logged into the registry on the same day of surgery. The median time to log the rest of the 26 cases was 1 day. Forty-two patients had a postoperative complication. The most common cause for severe complications was an anastomotic leak with a cumulative rate of 12.3. CONCLUSIONS: Re-designing the EMR to enable prospective documentation of surgical related data is a valid method to create an on-going, real-time database that is recorded instantaneously with minimal additional effort and minimal cost.

Transanal total mesorectal excision for rectal cancer: Surgical outcomes and short-term oncological outcomes in a single-institution consecutive series.

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.

The location of premalignant colorectal polyps under age 50: a further rationale for screening sigmoidoscopy.

PURPOSE: The incidence of colorectal cancer (CRC) among young adults has been dramatically rising, with guidelines for screening recently adjusted to start at age 45. However, knowledge of the precursor lesions is limited. We recently reported that 83% of CRC diagnosed under age 50 are left sided. Our aim was to analyze the location and histology of benign colorectal lesions found in a cohort of patients younger than 50, documenting the presence of advanced histology. METHODS: We used the database in the Department of Pathology to retrospectively review the location and histology of all benign colorectal neoplasms in patients under age 50 submitted to pathology examination during 2006-2016. RESULTS: A total of 8364 lesions were examined from 4773 patients, and 3534 (65.5%) of the patients had only one polyp and the rest had multiple. Mean age was 41.9 years (range 16-49) while 3843 (72.8%) of the patients were between the ages of 40 and 49. In total, 4570/8364 lesions (54.6%) were distal to the splenic flexure. The most common pathology was tubular adenoma (63.7%), then hyperplastic polyps (16.6%), sessile serrated lesions (SSLs) (13.1%), and tubulovillous adenomas (6.3%). Tubulovillous adenomas, villous lesions, advanced adenomas, and adenomas with high-grade dysplasia were all predominantly left sided (left colon and rectum = 77.6%, 85%, 78.3%, and 87.6% respectively). Of the SSLs, 71.5% were in the right colon while 16.6% of hyperplastic lesions were right sided. CONCLUSIONS: High-risk advanced adenomas are predominantly left sided. This focuses attention on the rectum and left colon where carcinogenesis is strong in the young.

Long-Term Bowel Function after Transanal Minimally Invasive Surgery (TAMIS).

BACKGROUND: Transanal minimally invasive surgery (TAMIS) is a single port access platform used for full thickness local excision of rectal lesions. It is an appealing alternative to a radical resection of rectum that often can cause a significant bowel dysfunction described as low anterior resection syndrome (LARS). LARS is evaluated using a validated score. Functional outcomes of patients undergoing TAMIS has not yet been evaluated using the LARS score. OBJECTIVES: To evaluate long-term bowel function in patients who underwent TAMIS. METHODS: In this case series, all patients who underwent TAMIS in a single tertiary institute between 2011 and 2017 were retrospectively reviewed. We evaluated bowel function using the LARS score questionnaire through telephone interviews. RESULTS: The study consisted of 23 patients, average age of 67 ± 6.98 year; 72% were male. The median follow-up from the time of surgery was 5 years. Six patients (26.08%) had malignant type lesions. The average height of the lesion from the anal verge was 7.4 cm. The average size of the specimen was 4 cm. The total LARS score revealed that 17 patients (73.91%) had no definitive LAR syndrome following the surgery. Four patients (17.39%) fit the description of minor LARS and only two (8.69%) presented with major LARS. CONCLUSIONS: TAMIS provides relatively good long-term functional outcomes in terms of bowel function. Further randomized studies with larger cohorts are still needed to better evaluate the outcomes.

The Impact of the COVID-19 Pandemic on General Surgery Acute Admissions and Urgent Operations: A Comparative Prospective Study.

BACKGROUND: As part of the effort to control the coronavirus disease-19 (COVID-19) outbreak, strict emergency measures, including prolonged national curfews, have been imposed. Even in countries where healthcare systems still functioned, patients avoided visiting emergency departments (EDs) because of fears of exposure to COVID-19. OBJECTIVES: To describe the effects of the COVID-19 outbreak on admissions of surgical patients from the ED and characteristics of urgent operations performed. METHODS: A prospective registry study comparing all patients admitted for acute surgical and trauma care between 15 March and 14 April 2020 (COVID-19) with patients admitted in the parallel time a year previously (control) was conducted. RESULTS: The combined cohort included 606 patients. There were 25% fewer admissions during the COVID-19 period (P < 0.0001). The COVID-19 cohort had a longer time interval from onset of symptoms (P < 0.001) and presented in a worse clinical condition as expressed by accelerated heart rate (P = 0.023), leukocyte count disturbances (P = 0.005), higher creatinine, and CRP levels (P < 0.001) compared with the control cohort. More COVID-19 patients required urgent surgery (P = 0.03) and length of ED stay was longer (P = 0.003). CONCLUSIONS: During the COVID-19 epidemic, fewer patients presented to the ED requiring acute surgical care. Those who did, often did so in a delayed fashion and in worse clinical condition. More patients required urgent surgical interventions compared to the control period. Governments and healthcare systems should emphasize to the public not to delay seeking medical attention, even in times of crises.

Incidence and Risk Factors for Anastomotic Leakage in Colorectal Surgery: A Historical Cohort Study.

BACKGROUND: Anastomotic leakage (AL) is a major complication following colorectal surgery, with many risk factors established to date. The incidence of AL varies in the medical literature and is dependent on research inclusion criteria and diagnostic criteria. OBJECTIVES: To determine the incidence of and the potential risk factors for AL following colorectal surgery at a single academic medical center. METHODS: We retrospectively reviewed all operative reports of colorectal procedures that included bowel resection and primary bowel anastomosis performed at Sheba Medical Center during 2012. AL was defined according to the 1991 United Kingdom Surgical Infection Study Group criteria. Data were assessed for leak incidence within 30 days. In addition, 17 possible risk factors for leakage were analyzed. A literature review was conducted. RESULTS: This cohort study comprised 260 patients, and included 261 procedures performed during the study period. The overall leak rate was 8.4%. In a univariate analysis, male sex (odds ratio [OR] 3.37, 95% confidence interval [95%CI] 1.21-9.43), pulmonary disease (OR 3.99, 95%CI 1.49-10.73), current or past smoking (OR 2.93, 95%CI 1.21-7.10), and American Society of Anesthesiologist score ≥ 3 (OR 3.08, 95%CI 1.16-8.13) were associated with an increased risk for anastomotic leakage. In a multivariate analysis, male gender (OR 3.62, 95%CI 1.27-10.33) and pulmonary disease (OR 4.37, 95%CI 1.58-12.10) were associated with a greater risk. CONCLUSIONS: The incidence of AL in the present study is similar to that found in comparable series. Respiratory co-morbidity and male sex were found to be the most significant risk factors.

[CYTOREDUCTIVE SURGERY AND HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC) FOR PERITONEAL METASTASIS OF GASTRO-INTESTINAL ORIGIN].

INTRODUCTION: The management of peritoneal surface malignancies has changed dramatically. Moving, in less than two decades, from a nihilistic approach offering limited palliation and a short median survival into an aggressive surgical approach combining resection of all tumor deposits (cytoreductive surgery (CRS) combined with hyperthermic intra-peritoneal chemotherapy (HIPEC). This novel approach dramatically changed the outcome of this group of disorders offering a long term survival with curative intent to selected patients. The aim of the current review is to describe, based on current medical literature and our experience, current treatment options with CRS+HIPEC in various peritoneal surface malignancies of gastrointestinal origin, namely, colorectal cancer and appendiceal cancer, indications, technique, and outcomes.

Hospital readmission rates and risk factors for readmission following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies.

BACKGROUND: Cytoreductive surgery and Hyperthermic intra-peritoneal chemotherapy (CRS/HIPEC) for peritoneal surface malignancies is associated with high morbidity. The increased numbers of patients undergoing CRS/HIPEC in recent years mandates risk analysis and quality assurance. However, only scarce data exist regarding causative parameters for readmission. The aim of this study was to assess readmission rates and risk factors associated with readmission. METHODS: A retrospective-cohort study including patients from two high-volume centers who underwent CRS/HIPEC surgery between the years 2007-2016 was performed. Patients' demographics, peri-operative data and readmission rates were recorded. RESULTS: 223 patients were included in the study. The 7 and 30-day readmission rates were 3.5% (n = 8) and 11% (n = 25), respectively. Late readmission rates (up to 90 days) were 11% (n = 25). The most common causes of readmission were surgical related infections (35%), small bowel obstruction (17.5%) and dehydration (14%). Post-operative complications were associated with higher readmission rates (p = 0.0001). PCI score was not associated with higher rates of readmission. CONCLUSION: Readmissions following CRS/HIPEC occur mainly due to infectious complications and dehydrations. Patients following CRS/HIPEC should be discharged after careful investigation to a community based continuing care with access for IV fluid replacement or antibiotics administration when required.