Experimental Model of Rectal Carcinogenesis Induced by N-Methyl-N-Nitrosoguanidine in Mice with Endoscopic Evaluation.

Background and purpose: The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods: Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. Results: We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Conclusion: Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia.

Hyperbaric oxygen therapy increases the effect of 5-fluorouracil chemotherapy on experimental colorectal cancer in mice.

Tumor hypoxia may compromise the results of chemotherapy for treating colorectal cancer because it stimulates angiogenesis and the release of tumor growth factors. Hyperbaric oxygen (HBO) supplementation may potentiate the effects of chemotherapy in such cases. This study aimed to assess the effect of HBO therapy combined with chemotherapy on the treatment of colorectal cancer in mice. C57BL6 mice were submitted to the intrarectal instillation of N-methyl-N-nitrosoguanidine (MNNG) and treated with 5-fluorouracil (5FU) and/or HBO therapy. The MNNG group presented the highest dysplastic crypt rate. The 5FU + HBO group presented the highest rate of apoptotic cells per dysplastic crypt. The 5FU group presented the highest expression of hypoxia-inducible factor-1 alpha and CD44. HBO therapy increased the effect of 5FU on the treatment of the experimental colorectal neoplasia in mice.

Relationship between academic performance and affective changes during the first year at medical school.

BACKGROUND: Entering medical school may be associated with changes in the students' life, which can affect academic motivation and impair academic performance. AIMS: This work aimed at measuring longitudinally academic motivation, anxiety, depression and social adjustment in first-year medical students and determining the relationships between these variables and academic performance, as measured mainly by grades on regular exams. METHODS: Eighty-five first-year medical students (age: 17-25 years) were included after giving informed consent. Beck's Anxiety (BAI) and Beck's Depression (BDI) Inventories, the self-reported Social Adjustment Scale (SAS-SR) and the Academic Motivation Scale (AMS) were applied two months after admission and at the end of the academic year. RESULTS: BAI scores increased throughout the year (7.3 ± 6.6 versus 28.8 ± 6.7; p < 0.001), whereas BDI scores did not change (6.8 ± 5.9 versus 6.0 ± 5.4; p > 0.10). SAS-SR subscales scores remained stable, except for a decreasing pattern for leisure/social life (1.8 ± 0.4 versus 2.1 ± 0.4; p < 0.001). AMS scores for motivation to know (22.2 ± 4.5 versus 19.7 ± 5.5; p < 0.001), to accomplish things to know (17.7 ± 5.3 versus 15.4 ± 5.3; p = 0.001), to experience to know (18.2 ± 5.2 versus 15.4 ± 5.4; p < 0.001) and by identification to know (23.5 ± 3.5 versus 21.8 ± 5.0; p = 0.002) decreased significantly. There were no significant correlations between academic performance and the global scores for any of the scales except for the SAS-SR subscale for academic life (r = -0.48, p < 0.001). CONCLUSIONS: Throughout the academic year, first-year medical students showed increased anxiety, decreased academic motivation and a maladjusted leisure/social life, which however does not seem to affect academic achievement.

Access to High-Cost Biological Agents: Perceptions of Brazilian Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Brazilian patients with inflammatory bowel diseases (IBD) requiring therapy with biological agents usually have access to medicines through the National Unified Health Care System (SUS). This study aimed to analyze Brazilian IBD patient perception regarding access (availability and provision quality) to high-cost drugs in the public health care system. METHODS: A questionnaire-based survey was carried out in an IBD referral center in Brazil. All adult patients with an established diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) that use biological therapy were invited to participate. Data were collected on the biological in use, lack of distribution (number of absences, average time to regularization, impairment in patient treatment), and difficulties reported by patients in obtaining the drugs. RESULTS: Overall, 205 patients met the inclusion criteria and answered the questionnaire. Most of the patients had CD (n = 161, 78.5%), nearly half of them (n = 104, 50.7%) were female; 87 patients (42.4%) were unemployed, and of these, 40 patients (19.5%) had government assistance as the main source of income. Regarding the medications used, infliximab (n = 128, 62.5%) was the most used medication, followed by adalimumab (n = 39, 19.0%). Most patients (n = 172, 83.9%) reported at least one failed delivery of biological medicine in the last year, with a single shortage in forty-two patients (24.4%), at least two shortages in forty-seven patients (27.3%), and three or more shortages in seventy-eight patients (45.3%). The average time to regularize the distribution was up to 1 month in 44 cases (25.6%), up to 2 months in 64 cases (37.2%), and more than 3 months in 56 patients (32.6%). Among patients who reported delays, 101 patients (58.7%) felt that it may have impaired their treatment. CONCLUSION: Brazilian IBD patients reported high rates of failure to dispense biological drugs by the national healthcare system within one year. Our data highlight the need for improvement in this system for the correct supply of medication to avoid treatment failure and relapse.

MAIN MANOMETRIC FINDINGS AND POTENTIAL FOR ANORECTAL PHYSICAL THERAPY IN THE TREATMENT OF PATIENTS WITH EVACUATION DISORDERS.

BACKGROUND: Evacuation disorders are prevalent in the adult population, and a significant portion of cases may originate from pelvic floor muscle dysfunctions. Anorectal manometry (ARM) is an important diagnostic tool and can guide conservative treatment. OBJECTIVE: To evaluate the prevalence of pelvic dysfunction in patients with evacuation disorders through clinical and manometric findings and to evaluate, using the same findings, whether there are published protocols that could be guided by anorectal manometry. METHODS: A retrospective analysis of a prospective database of 278 anorectal manometries performed for the investigation of evacuation disorders in patients seen at the anorectal physiology outpatient clinic of Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto between January 2015 to June 2019 was conducted. The following parameters were calculated: resting pressure (RP), squeeze pressure (SP), high-pressure zone (HPZ), rectal sensitivity (RS) and rectal capacity (RC). The pressure measurements and manometric plots were reviewed to determine the diagnosis and to propose potential pelvic physical therapy procedures. Analysis of variance (ANOVA) and Fisher's exact test were used to compare the continuous variables and to evaluate the equality of variances between groups of patients with fecal incontinence (FI) and chronic constipation (CC). Results with a significance level lower than 0.05 (P-value <0.05) were considered statistically significant. Statistical analysis was performed using IBM® SPSS® Statistics version 20. RESULTS: The mean age of the sample was 45±22 years, with a predominance of females (64.4%) and economically inactive (72.7%) patients. The indications for exam performance were FI (65.8%) and CC (34.2%). Patients with FI had lower RP (41.9 mmHg x 67.6 mmHg; P<0.001), SP (85.4 mmHg x 116.0 mmHg; P<0.001), HPZ (1.49 cm x 2.42 cm; P<0.001), RS (57.9 mL x 71.5 mL; P=0.044) and RC (146.2 mL x 195.5 mL; P<0.001) compared to those of patients with CC. For patients with FI, the main diagnosis was the absence of a functional anal canal (49.7%). For patients with CC, the main diagnosis was outflow tract obstruction (54.7%). For patients with FI, the main protocol involved a combination of anorectal biofeedback (aBF) with tibial nerve stimulation (TNS) (57.9%). For patients with CC, the most indicated protocol was aBF combined with TNS and rectal balloon training (RBT) (54.7%). CONCLUSION: There was a high prevalence of pelvic floor changes in patients with evacuation disorders. There was a high potential for performing pelvic floor physical therapy based on the clinical and manometric findings.

PPARG expression in colorectal cancer and its association with staging and clinical evolution.

Purpose To evaluate the gene expression of peroxisome proliferator activated receptors gamma (PPARG) in colorectal tumors and to correlate this data with clinical variables of the patients. Methods We analyzed the gene expression of PPARG in 50 samples of colorectal tumors using real-time reverse transcription polymerase chain reaction, and 20 adjacent normal tissue samples as control. The results of these quantifications were correlated with the respective patients' medical records' clinical information. Results PPARG expression was not different in the tumor tissue compared to the control tissue. Patients older than 60 years, histological type with mucinous differentiation, more advanced staging at the time of diagnosis, and patients who evolved with recurrence of the disease or death did not present higher PPARG expression. Conclusion Expression of PPARGD was not associated with worse prognosis.

Transanal endoscopic operation for rectal cancer after neoadjuvant therapy.

PURPOSE: In this paper we report the oncological outcomes from clinical series of patients with rectal cancer submitted to local excision after neoadjuvant therapy and discuss the indications for local excision in partial clinical responders. METHODS: We analysed a prospective database of 39 patients submitted to a transanal endoscopic operation for rectal cancer after neoadjuvant chemoradiation between 2006 and 2015, comparing clinical and pathological variables, perioperative complications, recurrence rate and overall survival. RESULTS: We obtained 15.4% ypT0, 17.9% ypT1, 35.9% ypT2 and 28.2% ypT3. After a median follow-up of 24 months, tumoral recurrence was observed in 4 patients, one of them with isolated pulmonary metastasis. R0 resection was achieved in 79.5%, and postoperative complications were observed in 30.2% patients and no perioperative mortality occur. Compromise surgical margins do not affect recurrence rate, and 94.9% of patients are alive nowadays. CONCLUSION: Local excision could be associated with low recurrence rate and good overall survival. Short hospitalization time and low level of serious complications observed could be an interesting option for patients who would not tolerate a radical procedure or for those who declined a total mesorectal excision. A strict long-term follow-up must be warranted to detect early tumoral recurrence.

A novel subcutaneous T-shaped bridge device for loop colostomies.

PURPOSE: To describe a novel securing device for loop colostomies, developed in our institution and report our 10-year experience. METHODS: The T-shaped support device was used in all patients who required loop colostomy and who were at an increased risk of stoma withdrawal. The device was removed on the fifth postoperative day in all patients. An analysis from a prospective database regarding early postoperative complication, from 209 patients, was conducted between 2003 and 2013. RESULTS: Bleeding, peristomal skin problems, surgical site infection, stomal ischemia/necrosis, stenosis, obstruction, retraction and early withdrawal of the stoma were not noted in all cases. Thirteen patients (6%) reported mild discomfort on the site of the skin suture. Removal of the instrument was fast and easy, with the advantage of keeping the colostomy bag. CONCLUSION: The T-shaped bridge device successfully prevented stoma withdrawal in all subjects. The device was safe and well accepted, with minor complications.

Infliximab-associated fulminant hepatic failure in ulcerative colitis: a case report.

INTRODUCTION: Infliximab, an antibody against tumor necrosis factor alpha, is used to treat inflammatory bowel disease and has well-established efficacy and proven safety. Complications of this treatment are related to immunosuppression and include higher risk of serious infections and malignant neoplasia. Although extremely rare, fulminant liver damage related to infliximab therapy has been reported. CASE PRESENTATION: We present the case of a 38-year-old Afro-Brazilian woman with refractory ulcerative colitis who was started on infliximab. She had no previous history of liver disease, alcohol abuse, or infection. After the fifth dose of the medication, drug-induced liver injury was diagnosed. Treatment was discontinued but our patient's condition was aggravated by severe cholestasis and grade III/IV encephalopathy, requiring liver transplantation. CONCLUSION: Drug-induced liver injury is an uncommon complication of infliximab. Current consensus recommends screening for liver dysfunction prior to and during therapy. This case emphasizes the need for vigilance and highlights a rare and potentially lethal complication.

A review of experimental models in colorectal carcinogenesis / Modelos experimentais de carcinogênese colorretal

Colorectal cancer is the leading cause of malignancy of the gastrointestinal tract. A better understanding of the molecular and cellular changes that lead to the disease is necessary to develop early diagnosis and optimal treatment modalities. Rodent models are rapid, reproducible and exhibit an adenoma-carcinoma sequence similar to that found in humans. The objective of this manuscript is to review the most common chemical carcinogens used to induce experimental tumors and the usual methods of evaluation.

O câncer colorretal é a principal neoplasia maligna do trato gastrointestinal. Um melhor entendimento dos processos moleculares e celulares é necessário para o desenvolvimento de estratégias que permitam um diagnóstico precoce e um tratamento mais eficaz. Modelos que utilizam roedores são rápidos, reprodutíveis e permitem o estudo da sequencia adenoma-carcinoma de forma similar a encontrada em humanos. O objetivo desse manuscrito é revisar os principais modelos de carcinogênese química e os métodos mais usuais para avaliação dos resultados.

Transanal endoscopic operation for rectal cancer after neoadjuvant therapy

PURPOSE: In this paper we report the oncological outcomes from clinical series of patients with rectal cancer submitted to local excision after neoadjuvant therapy and discuss the indications for local excision in partial clinical responders. METHODS: We analysed a prospective database of 39 patients submitted to a transanal endoscopic operation for rectal cancer after neoadjuvant chemoradiation between 2006 and 2015, comparing clinical and pathological variables, perioperative complications, recurrence rate and overall survival. RESULTS: We obtained 15.4% ypT0, 17.9% ypT1, 35.9% ypT2 and 28.2% ypT3. After a median follow-up of 24 months, tumoral recurrence was observed in 4 patients, one of them with isolated pulmonary metastasis. R0 resection was achieved in 79.5%, and postoperative complications were observed in 30.2% patients and no perioperative mortality occur. Compromise surgical margins do not affect recurrence rate, and 94.9% of patients are alive nowadays. CONCLUSION: Local excision could be associated with low recurrence rate and good overall survival. Short hospitalization time and low level of serious complications observed could be an interesting option for patients who would not tolerate a radical procedure or for those who declined a total mesorectal excision. A strict long-term follow-up must be warranted to detect early tumoral recurrence.

A novel subcutaneous T-shaped bridge device for loop colostomies

PURPOSE: To describe a novel securing device for loop colostomies, developed in our institution and report our 10-year experience. METHODS: The T-shaped support device was used in all patients who required loop colostomy and who were at an increased risk of stoma withdrawal. The device was removed on the fifth postoperative day in all patients. An analysis from a prospective database regarding early postoperative complication, from 209 patients, was conducted between 2003 and 2013. RESULTS: Bleeding, peristomal skin problems, surgical site infection, stomal ischemia/necrosis, stenosis, obstruction, retraction and early withdrawal of the stoma were not noted in all cases. Thirteen patients (6%) reported mild discomfort on the site of the skin suture. Removal of the instrument was fast and easy, with the advantage of keeping the colostomy bag. CONCLUSION: The T-shaped bridge device successfully prevented stoma withdrawal in all subjects. The device was safe and well accepted, with minor complications.