Oncological safety of transanal total mesorectal excision (TaTME) for rectal cancer: mid-term results of a prospective multicentre study

Background There is no consensus regarding the gold standard technique for rectal cancer as Total Mesorectal Excision (TME) may be safely performed either by open or minimally invasive surgery. The laparoscopic approach, however, may carry technical difficulties. For this reason, a novel technique has emerged in the last decade combining a dual laparoscopic dissection (abdominal and transanal) to perform the TME technique (TaTME). When focusing on oncological outcomes, there is a lack of literature regarding mid-long term results. The aim of this study is to evaluate the mid-term oncological impact of TaTME for treating rectal cancer. Methods A prospective multicentre study was performed in four tertiary centres including consecutive patients who underwent TaTME for mid-low rectal cancer by the same group of experienced surgeons. The analysed data included pathological results on the quality of TME and mid-term oncological outcomes. Results In total, 173 patients were included throughout a study period of 6 years. Our series included 70% males and 68% of patients with neoadjuvant treatments. The median follow-up was 23 [15–37.5] months. Regarding pathological results, a complete TME was achieved in 72.8%, while circumferential and distal margins were affected in 1.4 and 1.1%, respectively. Five patients developed local recurrences (3%) and 8.1% presented distant disease during the follow-up. The 2-year disease-free survival and the overall survival rates were 88% and 95%, respectively. Conclusions There is currently a lack of evidence in the literature regarding TaTME and oncological outcomes with no data available from randomized clinical trials. In the meantime, the reported results from different multicentre series are controversial. This study showed positive mid-term outcomes at 2 years of follow-up and supported notable oncological outcomes with TaTME. However, it must be emphasized that previous experience in minimally invasive and transanal surgeries is essential for surgeons before intending to perform TaTME

How to perform an anastomosis following a low anterior resection by transanal total mesorectal excision surgery: from top to bottom techniques

Aim: The aim was to describe the range of possibilities and our group's clinical outcomes when performing different types of anastomosis during transanal total mesorectal excision (taTME). Method: A retrospective analysis was performed based on four taTME series from 2016 to 2021. Inclusion criteria were patients with rectal cancer in whom a sphincter-saving low anterior resection by taTME was performed. Four different techniques were employed for the anastomosis construction: (A) abdominal view, (B) transanal view, (C) hand-sewn coloanal anastomosis and (D) pull-through. Intra-operative and postoperative data were collected and compared. Results: A total of 161 patients were included. Tumour height was lower in groups C and D (4 [3-5] vs. 7 [6-8] group A vs. 6 [5-7] group B, P = 0.000), requiring a hand-sewn anastomosis. A transanal extraction of the specimen was more commonly performed in groups C and D (over 60% vs. 30% in groups A and B, P = 0.000). The rate of temporary stoma was similar between groups A, B and C (ranging from 84% to 98%) but was significantly lower in group D (P = 0.000). The overall rate of complications was similar between groups; however, group D had longer length of stay (15 days vs. 5-6 in groups A, B and C, P = 0.026). Conclusion: Every type of anastomosis construction after a taTME procedure seems to be safe and feasible and should be chosen based on surgeon's experience, tumour height and the length of the rectal cuff after the rectal transection. Colorectal surgeons should be familiar with these techniques in order to choose the one that benefits each patient the most

Combined transanal minimally invasive surgery (TAMIS) and retroperitoneal laparoscopy for resection of lymph node recurrence of ovarian cancer

To our knowledge no cases of transanal minimally invasive surgery (TAMIS) combined with retroperitoneal laparoscopy for resection of lymph node recurrence have been described in the literature. We report a case of resection of mesorectal and para-aortic lymph node recurrence of primary ovarian cancer performed with retroperitoneal laparoscopy and TAMIS. A 66-year-old female, diagnosed in December 2014 with stage IIa ovarian adenocarcinoma had cytoreductive surgery at that time, achieving a R0 resection (complete hysterectomy with bilateral ovariectomy, pelvic peritonectomy with standard lymphadenectomy and supramesocolic omentectomy). Surgery was followed by adjuvant treatment. On November 2017, a computed tomography scan revealed lymph node recurrence in the left para-aortic nodes (2.5 cm diameter on CT) and mesorectal space (2.8 cm diameter) at 10 cm from the anal verge. After a multidisciplinary session, both nodes were resected (see attached video). The para-aortic node was resected using retroperitoneal laparoscopy and the mesorectal node resected using a TAMIS approach [1,2,3]. The postoperative course was uneventful and the patient was discharged 5 days after surgery. Histopathological examination of the two nodes revealed undifferentiated serosal adenocarcinoma of the ovary. No recurrence was found at 1-year follow-up. Combination of different minimally invasive approaches is a safe alternative to conventional surgery for resection of lymph node recurrence that surgeons should be aware of

Rectal cancer treatment by transanal total mesorectal excision: Results in 100 consecutive patients

Introduction The aim of this study is to describe and evaluate our clinical short-term surgical results of laparoscopic transanal total mesorectal excision. Methods Analysis of 100 consecutive patients with mid and lower rectal cancer who underwent transanal total mesorectal excision from November 2013 to September 2018. Main outcomes described are operative data, morbidities, mortality and quality of the specimen. A comparative analysis was done between gender and simultaneous versus non simultaneous abdominal-perineal surgery. Results Mean patient age was 67 years (56–75), and 67% were male. On MRI, 50% were stage T3 tumors, and 52% had positive nodes. Mean distance of the tumor from anal verge was 4.9±1.3cm. A total of 58% underwent neoadjuvant treatment. Mean operative time was 262±40.7min; it was shorter in females (P<.001) and in simultaneous 2-field surgery. Median specimen distal free margin was 1.5cm (0.5–2.4). A total of 89% of the specimens were with complete mesorectum, with better results when a simultaneous approach was used (P=.047). The mean number of retrieved lymph-nodes was 15.2±11.6, and 26% of patients had positive nodes. Median length of stay was 5.5 days (4–8). Morbidities occurred in 36% of cases, and one patient died. Conclusions According to our experience, laparoscopic transanal total mesorectal excision is safe and effective with adequate circumferential and distal free margins and high quality of the resected mesorectum specimen. Post-operative morbidity is acceptable, according to the current literature.Introducción El objetivo de este estudio es analizar los resultados quirúrgicos a corto plazo de la escisión completa del mesorrecto por vía transanal laparoscópica. Métodos Análisis en 100 pacientes con cáncer de recto medio e inferior, intervenidos consecutivamente entre noviembre de 2013 y septiembre de 2018. Se describen los datos operatorios, la morbimortalidad y la calidad de la pieza quirúrgica. Se realiza un análisis comparativo entre sexos y la cirugía a uno y a 2 campos simultáneos. Resultados La mediana de edad fue de 67 años (56–75), siendo el 67% varones. El 50% fueron tumores T3 y el 52% con afectación ganglionar, por RMN. La media de distancia al margen anal fue de 4,9±1,3cm. El 58% recibió neoadyuvancia. La media de tiempo quirúrgico fue de 262±40,7min, siendo menor en mujeres (p<0,001) y en la cirugía simultánea a 2 campos (p=0,008). La mediana de margen distal fue de 1,5cm (0,5-2,4). Se obtuvo un mesorrecto completo en el 89%, con mejores resultados en la cirugía a 2 campos (p=0,047). La media de ganglios aislados fue de 15,2±11,6. El 26% de los pacientes tuvieron afectación ganglionar. La mediana de estancia fue de 5,5 días (4-8). Hubo una morbilidad del 36% y un paciente falleció. Conclusiones La escisión completa del mesorrecto por vía transanal laparoscópica es segura, consiguiendo un adecuado margen circunferencial y distal, con una alta calidad del mesorrecto. Ofrece una morbilidad aceptable para el tipo de intervención quirúrgica, según la literatura actual

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review

Background Preoperative or neoadjuvant chemotherapy (NAC) has emerged as a novel alternative to treat locally advanced colon cancer (LACC), as in other gastrointestinal malignancies. However, evidence of its efficacy and safety has not yet been gathered in the literature. The aim of the present study was to perform an extensive review of the scientific evidence for NAC in patients with LACC. Methods PubMed, EMBASE, MEDLINE and Cochrane Library were searched for a systematic review of the literature from 2010 to 2019. Six eligible studies were included, with a total of 27,937 patients, 1232 of them (4.4%) treated with NAC. There were only one randomized controlled trial, three phase II non-randomized single arm studies and two retrospective studies. Results The baseline computed tomography scan showed that most of patients had a T3 tumor. The completion rate of the planned neoadjuvant treatment ranged from 52.5 to 93.8%. Between 97.2 and 100% of patients had the scheduled surgery. The median tumor volume reduction after NAC ranged from 62.5 to 63.7%. The anastomotic leak rate in the NAC group ranged from 0 to 7%, with no cases of postoperative mortality. There was major pathological tumor regression in 4–34.7% of cases. Between 84 and 100% of NAC patients had R0-surgery. Survival after NAC seems to be encouraging although significant improvement has only been proven in T4b tumours. Conclusions According to our systematic review, the NAC may be a safe and effective emerging therapeutic alternative for treating LACC. This approach, which is still being tested, increases the reliance on accurate radiological staging

The impact of SARS-CoV-2 infection on the surgical management of colorectal cancer: lessons learned from a multicenter study in Spain

Objective: the aim of the study was to analyze the management of colorectal cancer (CRC) patients diagnosed with CRC or undergoing elective surgery during the period of the SARS-CoV-2 pandemic. Material and methods: a multicenter ambispective analysis was performed in nine centers in Spain during a four-month period. Data were collected from every patient, including changes in treatments, referrals or delays in surgeries, changes in surgical approaches, postoperative outcomes and perioperative SARS-CoV-2 status. The hospital's response to the outbreak and available resources were categorized, and outcomes were divided into periods based on the timeline of the pandemic. Results: a total of 301 patients were included by the study centers and 259 (86 %) underwent surgery. Five hospitals went into phase III during the peak of incidence period, one remained in phase II and three in phase I. More than 60 % of patients suffered some form of change: 48 % referrals, 39 % delays, 4 % of rectal cancer patients had a prolonged interval to surgery and 5 % underwent neoadjuvant treatment. At the time of study closure, 3 % did not undergo surgery. More than 85 % of the patients were tested preoperatively for SARS-CoV-2. A total of nine patients (3 %) developed postoperative pneumonia; three of them had confirmed SARS-CoV-2. The observed surgical complications and mortality rates were similar as expected in a usual situation. Conclusions: the present multicenter study shows different patterns of response to the SARS-CoV-2 pandemic and collateral effects in managing CRC patients. Knowing these patterns could be useful for planning future changes in surgical departments in preparation for new outbreaks

Extracellular vesicles secreted by triple-negative breast cancer stem cells trigger premetastatic niche remodeling and metastatic growth in the lungs

Tumor secreted extracellular vesicles (EVs) are potent intercellular signaling platforms. They are responsible for the accommodation of the premetastatic niche (PMN) to support cancer cell engraftment and metastatic growth. However, complex cancer cell composition within the tumor increases also the heterogeneity among cancer secreted EVs subsets, a functional diversity that has been poorly explored. This phenomenon is particularly relevant in highly plastic and heterogenous triple-negative breast cancer (TNBC), in which a significant representation of malignant cancer stem cells (CSCs) is displayed. Herein, we selectively isolated and characterized EVs from CSC or differentiated cancer cells (DCC; EVsCSC and EVsDCC, respectively) from the MDA-MB-231 TNBC cell line. Our results showed that EVsCSC and EVsDCC contain distinct bioactive cargos and therefore elicit a differential effect on stromal cells in the TME. Specifically, EVsDCC activated secretory cancer associated fibroblasts (CAFs), triggering IL-6/IL-8 signaling and sustaining CSC phenotype maintenance. Complementarily, EVsCSC promoted the activation of α-SMA+ myofibroblastic CAFs subpopulations and increased the endothelial remodeling, enhancing the invasive potential of TNBC cells in vitro and in vivo. In addition, solely the EVsCSC mediated signaling prompted the transformation of healthy lungs into receptive niches able to support metastatic growth of breast cancer cells

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

Abstract Aim: It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC. Methods: We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by NewcastleeOttawa scale. Randomeffects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC. Results: Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n Z 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confi- dence interval [CI] 15.04e52.85, p Z 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n Z 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08e0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n Z 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20e2.06, p Z 0.02). There was moderate-to-high heterogeneity among the included studies. Conclusion: Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMAIR values

Residential proximity to industrial pollution sources and colorectal cancer risk: a multicase-control study (MCC-Spain)

Background: Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary. Objectives: To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Methods: MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects' residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders. Results: Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44-2.87) to 3 km (1.26; 1.00-1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77-4.00), surface treatment of metals (1.48; 1.08-2.02), glass and mineral fibers (2.06; 1.39-3.07), organic chemical industry (4.80; 3.20-7.20), inorganic chemical industry (6.74; 4.38-10.36), food/beverage sector (3.34; 2.38-4.68), and surface treatment using organic solvents (6.16; 4.06-9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91-14.28), antimony (5.30; 3.45-8.15), naphthalene (3.11; 2.16-4.49), organotin compounds (2.64; 1.76-3.98), manganese (2.53; 1.63-3.93), dichloromethane (2.52; 1.74-3.66), and vanadium (2.49; 1.59-3.91). Conclusions: Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer.This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) – EVP-1178/14); Spain's Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416); Carlos III Institute of Health (ISCIII) grants, cofunded by ERDF funds–a way to build Europe– (grants PI08/0533, PI08/1359, PI08/1770, PS09/00773-Cantabria, PS09/01286-Leon, PS09/01662-Granada, PS09/01903-Valencia, PS09/02078-Huelva, PI11/00226, PI11/01403, PI11/01810, PI11/01889-FEDER, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI14/01219, PI15/00069, PI15/00914, PI15/01032, PI17-00092); the Fundación Marqués de Valdecilla (API 10/09); the Junta de Castilla y León (LE22A10-2); the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); the Catalan Government DURSI grant 2014SGR647; the European Commission grants FOOD-CT-2006-036224-HIWATE; the Recercaixa (2010ACUP 00310); Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR72