Brazilian society of surgical oncology: Guidelines for the surgical treatment of mid-low rectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer in North America, Western Europe, and Brazil, and represents an important public health problem. It is estimated that approximately 30% of all the CRC cases correspond to tumors located in the rectum, requiring complex multidisciplinary treatment. In an effort to provide surgeons who treat rectal cancer with the most current information based on the best evidence in the literature, the Brazilian Society of Surgical Oncology (SBCO) has produced the present guidelines for rectal cancer treatment that is focused on the main topics related to daily clinical practice. OBJECTIVES: The SBCO developed the present guidelines to provide recommendations on the main topics related to the treatment of mid-low rectal cancer based on current scientific evidence. METHODS: Between May and June 2021, 11 experts in CRC surgery met to develop the guidelines for the treatment of mid-low rectal cancer. A total of 22 relevant topics were disseminated among the participants. The methodological quality of a final list with 221 sources was evaluated, all the evidence was examined and revised, and the treatment guideline was formulated by the 11-expert committee. To reach a final consensus, all the topics were reviewed via a videoconference meeting that was attended by all 11 of the experts. RESULTS: The prepared guidelines contained 22 topics considered to be highly relevant in the treatment of mid-low rectal cancer, covering subjects related to the tests required for staging, surgical technique-related aspects, recommended measures to reduce surgical complications, neoadjuvant strategies, and nonoperative treatments. In addition, a checklist was proposed to summarize the important information and offer an updated tool to assist surgeons who treat rectal cancer provide the best care to their patients. CONCLUSION: These guidelines summarize concisely the recommendations based on the most current scientific evidence on the most relevant aspects of the treatment of mid-low rectal cancer and are a practical guide that can help surgeons who treat rectal cancer make the best therapeutic decision.

Robotic rectal surgery: Outcomes of the first 102 totally robotic cases handled using the single-docking technique in a reference institution.

BACKGROUND AND OBJECTIVE: Rectal cancer is often surgically treated, but it is still associated with morbidity rates. Minimally invasive techniques are increasingly being used to reduce complications, and the use of such techniques can be found in the literature. This study aims to report our experience in a reference oncology center. METHODS: A retrospective cohort study was performed on a prospective database of patients who underwent robotic surgery for rectal cancer using the single-docking technique from September 2014 to April 2018. Clinical and surgical variables, as well as morbidity and mortality rates, were analyzed. RESULTS: One hundred and two patients underwent robotic surgery. Intraoperative complications occurred in six patients (4.9%), and postoperative complications in 24 patients (23.5%), of which anastomotic fistula represented 3.9%. The conversion rate was 1.96%. Two cases (1.9%) faced death within 30 days. The median length of hospitalization was 3 days. The median number of lymph nodes dissected was 15. Clinical and surgical data were correlated with postoperative complications, and no statistically significant differences were found. CONCLUSION: Robotic surgery is a safe and feasible approach to manage rectal cancer. The method presents satisfactory results with regard to the rate of operative complications, conversion rate, oncologic outcomes, and length of hospitalization.

The Performance of Colorectal Cancer Screening in Brazil: The First Two Years of the Implementation Program in Barretos Cancer Hospital.

Colorectal cancer is the second most common cancer in Brazil. Yet, a nationally organized colorectal screening program is not implemented. Barretos Cancer Hospital (BCH) is one of the largest Brazilian institution that cares for underserved patients. BCH developed a fecal immunochemical test (FIT)-based organized colorectal cancer screening program to improve colorectal cancer outcomes.This study aims to present the quality/performance measures of the first 2 years of the FIT-based colorectal cancer screening program and its impact on the colorectal cancer disease stage. Between 2015 and 2017, a total of 6,737 individuals attending the Outpatient Department of Prevention or the Mobile Unit of BCH, which visits 18 cities of Barretos county, ages 50 to 65 years, were personally invited by a health agent/nurse practitioner. Exclusion criteria were personal history of colorectal cancer, adenomatous polyps, inflammatory bowel disease, and colonoscopy, or flexible sigmoidoscopy performed in the past 5 years. European Union (EU) guidelines for colorectal cancer screening programs were evaluated. Overall, 92.8% returned the FIT, with an inadequate examination rate of 1.5%. Among the 6,253 adequately tested, 12.5% had a positive result. The colonoscopy compliance and completion rates were 84.6 and 98.2%, respectively. The PPVs were 60.0%, 16.5%, and 5.6% for adenoma, advanced adenoma, and cancer, respectively. Stage distribution of screen-detected cancers shows earlier stages than clinically diagnosed colorectal cancer cancers reported at BCH and Brazilian cancer registries. Our colorectal cancer screening program achieved desirable quality metrics, aligned with the EU guidelines. The observed shift toward earlier colorectal cancer stages suggests an exciting opportunity to improve colorectal cancer-related cancers in Brazil.

Multicenter Controlled Study of Intracorporeal Mechanical Side-to-Side Isoperistaltic Anastomosis versus Extracorporeal Anastomosis in Laparoscopic Right Hemicolectomy: HEMI-D-TREND-Study.

Colorectal cancer is the second most frequent cancer in the Western world. A third of colorectal tumors are located in the right colon, and right hemicolectomy is the treatment in nondisseminated right colon cancer. The most serious complication of this procedure is anastomotic leak, which occurs in 8.4% of cases. At present, there is no standardized technique for laparoscopic ileo-colic anastomosis. In previous observational studies, intracorporeal side-to-side ileo-colic laparoscopic anastomosis has shown better results than extracorporeal anastomosis in terms of morbidity and mortality. It is known that randomized studies provide higher levels of evidence, but multicenter randomized controlled studies may imply a learning curve bias due to the differences in technical experience acquired at each hospital. As a result, we propose to carry out a prospective, controlled, nonrandomized TREND-study design (Transparent Reporting of Evaluations with Non-randomized Designs-TREND) in a large sample of 416 patients (208 per group) in order to assess the use of intracorporeal side-to-side ileo-colic laparoscopic anastomosis as the gold standard in right hemicolectomy.

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies. Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

Loss of Raf kinase inhibitor protein expression is associated with human papillomavirus 16 infection in anal tumors.

There has been an increase in the incidence of anal cancer in the past two decades, with squamous cell carcinoma (SCC) being the most frequent histological type identified. Among the risk factors, high-risk human papillomavirus (HPV) infection is the most pervasive. Raf kinase inhibitor protein (RKIP) is expressed in a number of normal human tissues and previous studies have demonstrated the prognostic value of the loss of RKIP expression in several gastrointestinal tumors. Therefore, the present study aimed to evaluate the clinical implications of RKIP expression in a series of neoplastic lesions of the anal canal. The resected tumors of 48 patients [8 high-grade intraepithelial lesions (HSILs), 14 adenocarcinomas and 26 squamous cell carcinomas (SCCs)] were immunohistochemically evaluated for RKIP expression, and the results were correlated with clinicopathological data. The results identified a decreased 5-year overall survival rate in patients with adenocarcinoma (40.8%) compared with patients with SCC (76.7%), and a decreased 5-year disease-free survival rate in patients at clinical stages III/IV (37.3 vs. 62.5 and 82.6% for clinical stages 0 and I/II, respectively). Low RKIP expression was revealed in 62.5% of HSILs, 88.5% of SCCs and 100.0% of the adenocarcinomas. High RKIP expression was associated with patient ethnicity (37.5% in non-Caucasians vs. 7.5% in Caucasians) and patient age (33.3% in younger patients vs. 0.0% in older patients). Finally, high RKIP expression was correlated with HPV16 infection status (40% in HPV- vs. 5.3% in HPV+ patients). A correlation was identified between high RKIP expression and lesions with a generally improved prognosis, such as those diagnosed in younger patients, in situ lesions and lesions of lower clinical grades; there was also a negative correlation between high RKIP expression and HPV16 positivity in patients.

Characterization of topoisomerase II α and minichromosome maintenance protein 2 expression in anal carcinoma.

The present study aimed to ascertain the significance of topoisomerase II α (TOP2A) and minichromosome maintenance protein (MCM) 2 expression in anal carcinoma. A total of 75 anal lesions were retrieved from the files of the Department of Pathology of Barretos Cancer Hospital (Barretos, Brazil) in order to verify the human papillomavirus (HPV) statuses of these lesions and characterize the immunohistochemical expression levels of TOP2A and MCM2 in anal carcinoma, as these are important markers for cervical HPV-induced lesions; their expression was also compared with respect to p16 and Ki-67. The vast majority of the cases tested positive for HPV16 (84%); 1 case tested positive for both HPV16 and HPV18. Positive HPV16 status was more frequent in early stages than in advanced stages (P=0.008). Positive immunohistochemical reactivity for MCM2 and TOP2A protein was observed in 71.6 and 100% of cases, respectively. Positive reactivity for p16 was significantly associated (P=0.001) with histological grade, and was more commonly expressed in squamous cell carcinoma than adenocarcinomas. HPV16 was strongly associated with positive p16 protein expression (76.6%). However, the high expression of Ki-67 combined with the high expression of p16 was predominantly observed in Stage III-IV cases. MCM2, TOP2A, p16 and Ki-67 exhibited intense positive staining in the anal lesions, indicating that these markers were significantly and constantly expressed in anal carcinoma.

Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors.

Anal cancer is a rare type of digestive tract disease, which has had a crescent incidence in a number of regions. Carcinomas are most frequently found, with squamous cell carcinoma (SCC) comprising ~95% of all anal tumors. The major risk factor for development of this type of tumor is human papillomavirus (HPV) infection. However, previous studies have identified patients with anal cancer that are HPV­/p16­and observed that they have a poorer outcome compared with HPV+/p16+ patients. This suggests that molecular profile may drive anal cancer progression. The aim of the present study was to evaluate the mutational status of two important oncogenes, KRAS and BRAF, in a series of anal cancer lesions. Resected tumors of the anal canal (n=43) were evaluated, nine of these were high­grade squamous intra­epithelial lesion cases (HSIL), 11 were adenocarcinomas, and 23 SCCs. Direct sequencing of KRAS proto­oncogene, GTPase (KRAS; codons 12 and 13) and B­Raf proto­oncogene, serine/threonine kinase (BRAF; codon 600) was performed and associated with patient clinicopathological and molecular features. There was a trend of poorer prognosis of adenocarcinoma compared with HSIL and SCC. Analysis indicated one SCC patient (2.3%) exhibited a KRAS p.G13D mutation, and one adenocarcinoma patient (2.3%) exhibited a BRAF p.V600E mutation. It was observed that, these mutations are rare in anal tumors, and certain patients may be at a disadvantage using targeted therapies based on KRAS and BRAF mutational status. As there is a low mutation percentage in SCCs, adenocarcinomas and HSIL, there may exist other underlying molecular alterations that result in anal cancer development, which require further elucidation.

Clinical characteristics of women diagnosed with carcinoma who tested positive for cervical and anal high-risk human papillomavirus DNA and E6 RNA.

High-risk human papillomavirus (hrHPV) is an essential cause of cervical carcinoma and is also strongly related to anal cancer development. The hrHPV E6 oncoprotein plays a major role in carcinogenesis. We aimed to evaluate the frequency of hrHPV DNA and E6 oncoprotein in the anuses of women with cervical carcinoma. We analyzed 117 women with cervical cancer and 103 controls for hrHPV and the E6 oncogene. Positive test results for a cervical carcinoma included 66.7 % with hrHPV-16 and 7.7 % with hrHPV-18. One case tested positive for both HPV variants (0.9 %). The samples from the anal canal were positive for HPV-16 in 59.8 % of the cases. Simultaneous presence of HPV in the cervix and anal canal was found in 53.8 % of the cases. Regarding expression of E6 RNA, positivity for HPV-16 in the anal canal was found in 21.2 % of the cases, positivity for HPV-16 in the cervix was found in 75.0 %, and positivity for HPV-18 in the cervix was found in 1.9 %. E6 expression in both the cervix and anal canal was found in 19.2 % of the cases. In the controls, 1 % tested positive for HPV-16 and 0 % for HPV-18. Anal samples from the controls showed a hrHPV frequency of 4.9 % (only HPV16). The presence of hrHPV in the anal canal of women with cervical cancer was detected at a high frequency. We also detected E6 RNA expression in the anal canal of women with cervical cancer, suggesting that these women are at risk for anal hrHPV infection.

Laparoscopic mobilization for resection of the transverse colon for cancer: a simple, reproducible method.

Laparoscopic resection for colorectal cancer by appropriately skilled surgeons is now accepted as safe and oncologically sound. Much of the contemporary debate in this area is regarding appropriate training of surgeons, as there is a steep learning curve. Arguably, the most difficult aspect of laparoscopic colon resection is mobilization of the transverse colon, with division of the middle colic artery. Mobilizing the transverse colon is necessary for many colonic resections, including "introductory" procedures. Our department has a consistent, sequential method for mobilization of the transverse colon with proximal isolation and ligation of the middle colic artery as indicated. This involves using the head, or distal body, of the pancreas as a landmark, for right-sided and left-sided resections, respectively. We believe that this particular methodology is easy to learn and surgically efficient. We also discuss some particular intraoperative problems and scenarios, with suggested solutions.

Study on the prevalence of human papillomavirus in the anal canal of women with cervical intraepithelial neoplasia grade III.

OBJECTIVE: The objective was to evaluate the prevalence of human papillomavirus (HPV) in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade III. STUDY DESIGN: Two groups were compared. In group I (study group), 40 women who had undergone cervical biopsy with a histopathological result indicating CIN III were evaluated. Group II (control) consisted of 40 women with normal results from colposcopic examination and colpocytological tests. The women in group I who presented high-grade neoplasia in colpocytological tests underwent collection of material from the uterine cervix and anal canal for investigating HPV DNA using the Hybrid Capture II technique. Colposcopy and cervical biopsy were then performed. If CIN III was confirmed, HPV DNA was investigated in the material collected. In group II, colpocytological tests and colposcopy were performed and, if normal, the procedure was similar to that followed for group I, except that no biopsy was performed. RESULTS: In group I, 39 women (97.5%) were positive for HPV in the uterine cervix and 14 women (35%) in the anal canal. In group II, only four women (10%) had a positive HPV test, for both the uterine cervix and the anal canal. CONCLUSIONS: The prevalence of HPV in the anal canal of the women with CIN III was greater than in the women without CIN III.

Estudo da expressão da proteína caderina-E correlacionada com o grau de diferenciação celular e o estadiamento TNM do adenocarcinoma colorretal / Relationship study between the cadherin-E protein cell diferentiation and TNM staging

OBJETIVO: Avaliar a relação de uma proteína que participa do mecanismo de adesão celular com o grau de diferenciação celular e o estadiamento TNM I e IV no CCR. MÉTODOS: Foram estudados 100 pacientes (54 homens e 46 mulheres) tratados por CCR, estádio I - 44 pacientes, estádio IV - 56 pacientes. Os cortes histológicos do tecido tumoral foram examinados por técnica de imunohistoquímica em relação à expressão da proteína caderina-E. Os cortes histológicos foram classificados como positivos ou negativos pelo método semiquantitativo. RESULTADOS: Para o TNM, expressão da caderina-E estádio I: positiva em 72,7 por cento e negativa em 35,7 por cento ; estádio IV: positiva em 64,3 por cento e negativa em 35,7 por cento. Em relação ao grau de diferenciação celular, expressão da caderina-E; G I: positiva em 70 por cento e negativa em 30 por cento; G II: positiva em 68.4 por cento e 31,6 por cento negativa; G III: 63.6 por cento positiva e 36,4 por cento negativa.. Não houve diferença significativa entre os grupos. CONCLUSÃO: Os resultados dessa pesquisa permitem concluir que não há relação da expressão da proteína caderina-E com o estadiamento TNM (I e IV) e o grau de diferenciação celular no CCR.

OBJECTIVE: To evaluate the relationship of a protein that take part in the same mechanism of cell adhesion with the cell differentiation degree and TNM staging I and IV in CRA. METHODS: One-hundred patients (54 men and 46 women), who have received treatment for CRA, stage I - 44 patients and stage IV - 56 patients, have been studied. Histological cuts of tumor tissue were examined by the immunohistochemical technique as to the expression of E-cadherin proteins. Such histological cuts were classified as positive or negative through the semi-quantitative method. RESULTS: For TNM, the E-cadherin expression for stage I: positive in 72.7 percent and negative in 35.7 percent; stage IV: positive in 64.3 percent and negative in 35.7 percent. Regarding the cell differentiation degree, the expression of E-cadherin, GI: positive in 70 percent and negative in 30 percent; GII: positive in 68.4 percent and negative in 31.6 percent; GIII: positive in 63.6 percent and negative in 36.4 percent. There was no significant difference among the groups. CONCLUSION: The results of this research come to the conclusion that there is no relationship between the expression of E-cadherin protein with TNM staging (I and IV) and cell differentiation degree in CRA.