Factors associated with surgical resection in patients with Crohn's disease: long-term evaluation.

PURPOSE: To evaluate patient characteristics and factors associated with surgical resection in patients with Crohn's disease (CD). METHODS: An analysis was performed on data from 295 patients with CD in follow-up from 2001 to 2018. Medical record data comprised age, gender, location, behavior and duration of the CD, smoking, and extraintestinal manifestation. Patients were divided into two groups according to the presence or absence of surgical resection. RESULTS: Out of the 295 patients with CD, 155 underwent surgical resection (53.2% male, mean age: 43.88 ± 14.35 years). The main indications for surgery were stenosis (44.5%), clinical intractability (15.5%), and intra-abdominal fistulas (15.5%). Smoking (p < 0.001), longer CD duration (p < 0.0001), ileo-colonic location (p = 0.003), stenosing behavior (p < 0.0001), and fistulizing behavior (p < 0.0001) were significantly associated with surgical resection. Initial use of biological was significantly more frequent in the group of patients without surgical resection (p < 0.001). CONCLUSIONS: Patients with CD still frequently need surgical treatment. Smoking (current or past), longer disease time, stenosing and fistulizing behavior, and ileo-colonic localization in CD patients were associated with a higher risk of surgery. Awareness about factors associated with unfavorable outcome allows such patients to be treated more appropriately.

Leukocyte dysfunction and reduced CTLA-4 expression are associated with perianal Crohn's disease.

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present a history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-γ, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management.

Factors associated with surgical resection in patients with Crohn's disease: long-term evaluation

ABSTRACT Purpose: To evaluate patient characteristics and factors associated with surgical resection in patients with Crohn's disease (CD). Methods: An analysis was performed on data from 295 patients with CD in follow-up from 2001 to 2018. Medical record data comprised age, gender, location, behavior and duration of the CD, smoking, and extraintestinal manifestation. Patients were divided into two groups according to the presence or absence of surgical resection. Results: Out of the 295 patients with CD, 155 underwent surgical resection (53.2% male, mean age: 43.88 ± 14.35 years). The main indications for surgery were stenosis (44.5%), clinical intractability (15.5%), and intra-abdominal fistulas (15.5%). Smoking (p < 0.001), longer CD duration (p < 0.0001), ileo-colonic location (p = 0.003), stenosing behavior (p < 0.0001), and fistulizing behavior (p < 0.0001) were significantly associated with surgical resection. Initial use of biological was significantly more frequent in the group of patients without surgical resection (p < 0.001). Conclusions: Patients with CD still frequently need surgical treatment. Smoking (current or past), longer disease time, stenosing and fistulizing behavior, and ileo-colonic localization in CD patients were associated with a higher risk of surgery. Awareness about factors associated with unfavorable outcome allows such patients to be treated more appropriately.

Evaluation of the response rate to neoadjuvant chemoradiotherapy in patients with rectal adenocarcinoma: a retrospective long-term study in two terciary reference centers

Objectives: To evaluate the complete response (CR) rate and surgeries performed in patients with rectal adenocarcinoma who underwent neoadjuvant therapy (NT) at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Hospital São Paulo, in Ribeirão Preto, from January 2007 to December 2017. Methods: We evaluated 166 medical records of patients with locally advanced rectal adenocarcinoma (T3, T4 or N+) who underwent NT. The regimen consisted of performing conventional (2D) or conformational (three-dimensional-3D/ radiotherapy with modulated intensity - IMRT) at a dose of 45-50.4Gy associated with capecitabine 1650mg/m2 or 5-fluorouracil (5FU) and leucovorin (LV). The following variables were analyzed: gender, age, pretreatment stage, radiotherapy, CR index, local and distant recurrence rates. Surgical treatment and complications were also evaluated. Results: The CR index was 28.3%. Patients treated with 3D/IMRT radiotherapy had a higher rate of CR (36.3% x 4.8%; p < 0.001), higher rates of clinical follow-up (21% x 0%; p < 0.001), lower surgery rates (79% x 100%; p < 0.001), higher rates of transanal resection (37.1% x 9.5%; p = 0.001), lower rates of abdominal rectosigmoidectomy (25.8% x 50%; p = 0.007) and lower rates of abdominoperineal resection of the rectum (16.1% x 40.5%; p = 0.002), when compared to patients treated with 2D radiotherapy. Conclusion Modern radiotherapy techniques such as 3D conformal and IMRT, by offering greater adequacy and precision of treatment, could result in better local control and less toxicity in organs at risk, enabling organ preservation strategies and less invasive approaches in selected cases. (AU)

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology.

INTRODUCTION: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. PURPOSE: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. METHODS: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. RESULTS: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. CONCLUSIONS: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

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.

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology / Análise retrospectiva dos resultados cirúrgicos e oncológicos em cirurgias videolaparoscópicas realizadas por residentes de coloproctologia

ABSTRACT Introduction: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. Purpose: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. Methods: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. Results: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. Conclusions: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

RESUMO Introdução: com o aperfeiçoamento e a ampla aceitação da laparoscopia nas operações colorretais, houve necessidade de treinamento específico dos cirurgiões em formação. Existem poucos estudos avaliando os resultados pós operatórios das colectomias videolaparoscópicas realizadas por médicos residentes e seu impacto na segurança do paciente. Objetivo: analisar os resultados cirúrgicos e oncológicos das colectomias videolaparoscópicas realizadas por residentes de coloproctologia e comparar com dados da literatura. Métodos: trata-se de uma análise retrospectiva de pacientes submetidos a cirurgias colorretais laparoscópicas, realizadas por médicos residentes do Hospital das Clínicas de Ribeirão Preto, entre 2014 e 2018. Foram estudadas as características clínicas dos pacientes bem como os principais aspectos cirúrgicos e oncológicos em um período de um ano. Resultados: analisou-se 191 operações, cuja principal indicação cirúrgica foi adenocarcinoma, a maioria estadio III. A duração média das cirurgias foi 210±58 minutos. Houve necessidade de estoma em 21,5% dos pacientes, principalmente colostomia em alça. A taxa de conversão foi 23%, sendo 79,5% por dificuldades técnicas, e os principais fatores preditores de conversão foram obesidade e acidentes intra-operatórios. A mediana do tempo de internação foi 6 dias. Anemia pré operatória associou-se a uma maior taxa de complicações (11,5%) e reoperações (12%). Houve comprometimento das margens de ressecção cirúrgica em 8,6% dos casos. A taxa de recidiva em um ano foi de 3,2%, e a taxa de mortalidade, 6,3%. Conclusões: a cirurgia colorretal videolaparoscópica realizada por residentes apresentou eficácia e segurança semelhante aos dados encontrados na literatura.

Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn's disease: a real-world multicenter Brazilian study.

BACKGROUND: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. METHODS: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. RESULTS: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. CONCLUSIONS: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

Preservation of the superior rectal artery in laparoscopic colectomy for slow transit constipation: Is it really associated with better outcomes?

Few patients with slow-transit constipation refractory to conservative treatment can benefit with a subtotal colectomy with ileorectal anastomosis with the preservation of the superior rectal artery. In this letter to the editor some important issues were discussed. First, the study did not include a comparison group. Second, they did not present the functional results in the short or long term related to the bowel function of these patients after surgery. Finally, the authors showed that this surgical procedure was safe, and no cases of leakage were found.

TEACHING BASIC COLONOSCOPY SKILLS: QUALITY AND SAFETY STANDARDS CAN BE FULFILLED IN AN OUTPATIENT UNIVERSITY CENTER.

BACKGROUND: Recent studies have shown that endoscopy fellows can perform colonoscopy effectively and safely. However, little is known about the performance of surgical residents without prior knowledge of endoscopic techniques. OBJECTIVE: To assess whether quality indicators were met at an outpatient endoscopy center and whether surgical residents, without prior upper or lower endoscopy skills, could perform colonoscopy adequately. METHODS: A prospective non-randomized cohort study was undertaken. All exams were performed either by assistant physicians or by residents. Quality measures were compared between those groups. RESULTS: A total of 2720 colonoscopies were analyzed. In the resident group, we observed older patients (57.7±12.7 years vs 51.5±14.5 years, P<0.001), a higher prevalence of screening colonoscopies (52% vs 39.4%, P<0.001) and a higher prevalence of colorectal cancer (6.4% vs 1.8%, P<0.001). The cecal intubation rate was higher in the attending group (99.9% vs 89.3%; P<0.001). The polyp detection rate was 40.8%, and no differences were observed between the studied groups. The residents had a higher rate of perforation in all exams (0.4% vs 0%; P=0.02). Postpolypectomy bleeding and 7-day readmission rates were the same (0.2%). All readmissions in 7 days occurred due to low digestive bleeding, and none required intervention. CONCLUSION: Quality indicators were met at a university outpatient endoscopy center; however, medical residents achieved lower rates of cecal intubation and higher rates of perforation than the attending physicians.

Ensino das habilidades básicas de colonoscopia: os padrões de qualidade e segurança podem ser atendidos em um centro universitário / Teaching basic colonoscopy skills: quality and safety standards can be fulfilled in an outpatient university center

ABSTRACT BACKGROUND: Recent studies have shown that endoscopy fellows can perform colonoscopy effectively and safely. However, little is known about the performance of surgical residents without prior knowledge of endoscopic techniques. OBJECTIVE: To assess whether quality indicators were met at an outpatient endoscopy center and whether surgical residents, without prior upper or lower endoscopy skills, could perform colonoscopy adequately. METHODS: A prospective non-randomized cohort study was undertaken. All exams were performed either by assistant physicians or by residents. Quality measures were compared between those groups. RESULTS: A total of 2720 colonoscopies were analyzed. In the resident group, we observed older patients (57.7±12.7 years vs 51.5±14.5 years, P<0.001), a higher prevalence of screening colonoscopies (52% vs 39.4%, P<0.001) and a higher prevalence of colorectal cancer (6.4% vs 1.8%, P<0.001). The cecal intubation rate was higher in the attending group (99.9% vs 89.3%; P<0.001). The polyp detection rate was 40.8%, and no differences were observed between the studied groups. The residents had a higher rate of perforation in all exams (0.4% vs 0%; P=0.02). Postpolypectomy bleeding and 7-day readmission rates were the same (0.2%). All readmissions in 7 days occurred due to low digestive bleeding, and none required intervention. CONCLUSION: Quality indicators were met at a university outpatient endoscopy center; however, medical residents achieved lower rates of cecal intubation and higher rates of perforation than the attending physicians.

RESUMO CONTEXTO: Estudos recentes mostraram que médicos em treinamento podem realizar a colonoscopia de maneira eficaz e segura. No entanto, pouco se sabe sobre a performance dos médicos residentes de cirurgia sem o conhecimento prévio das técnicas endoscópicas. OBJETIVO: Avaliar se os indicadores de qualidade foram atendidos em um centro de endoscopia ambulatorial e se os residentes de cirurgia, sem habilidades anteriores em endoscopia alta ou baixa, realizaram a colonoscopia de forma adequada. MÉTODOS: Foi realizado um estudo de coorte prospectivo não randomizado. Todos os exames foram realizados por médicos assistentes ou residentes. Os indicadores de qualidade foram comparados entre esses grupos. RESULTADOS: Um total de 2.720 colonoscopias foram analisadas. No grupo de médicos residentes, observamos pacientes mais velhos (57,7±12,7 anos vs 51,5±14,5 anos, P<0,001), maior prevalência de colonoscopias de rastreamento (52% vs 39,4%, P<0,001) e maior prevalência de câncer colorretal (6,4% vs 1,8%, P<0,001). A taxa de intubação cecal foi maior no grupo de médicos assistentes (99,9% vs 89,3%; P<0,001). A taxa de detecção de pólipos foi de 40,8% e não foram observadas diferenças entre os grupos estudados. Os médicos residentes tiveram maior índice de perfuração (0,4% vs 0%; P=0,02). O sangramento pós-polipectomia e as taxas de readmissão em 7 dias foram iguais (0,2%). Todas as readmissões em 7 dias ocorreram devido a hemorragia digestiva baixa e nenhuma intervenção foi necessária. CONCLUSÃO: Os indicadores de qualidade foram alcançados em um centro de endoscopia universitário; no entanto, os médicos residentes alcançaram taxas mais baixas de intubação cecal e taxas mais altas de perfuração do que os médicos assistentes.

A novel technique for superficial complicated stomas using the Dacron vascular prosthesis.

BACKGROUND AND PURPOSE: Despite the advances achieved in surgical techniques in recent years, an intestinal stoma is still needed in many patients undergoing colorectal surgery. However, the intestinal stoma may be associated with serious complications and the need for a second surgical procedure. In extreme cases, when it is not possible to access the abdominal cavity, the management of a complicated stoma is challenging. The purpose of this study was to describe the use of a Dacron vascular prosthesis (DVP) in patients with intestinal stoma complications. METHODS: In patients with a shallow, superficial stoma or mucocutaneous separation (MCS), we sutured the prosthesis in the intestinal loop (at the edge of an intestinal fistula) to create a device to direct the fecal content to the collection bag. RESULTS: We included 9 patients in this series (colorectal cancer, n = 5; Crohn's disease, n = 2; giant abdominal hernia and morbid obesity, n = 2). The results obtained were promising since they showed good evolution in patients with severe intestinal complications and an impossibility of surgical correction of the stoma. Five patients presented complete healing, and two patients presented partial healing. There were two deaths caused by sepsis, which were not related to the surgical procedure. With this technique, there was a reduction in the leakage of intestinal contents into the peritoneal cavity and an increase in the healing of the peristomal dermatitis in most of the patients. The DVP could possibly represent a surgical alternative in selected patients with complicated stomas when surgical correction may not be a suitable option. CONCLUSIONS: The authors recommend this technique for selected complex cases of stoma complications after unsuccessful attempts to adapt collecting equipment. The placement of the DVP allowed the peristomal skin to heal and improved the contamination of the peritoneal cavity.

ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition. METHODS: Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients. RESULTS: Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples. CONCLUSION: Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration.

COVID-19 quarantine measures are associated with negative social impacts and compromised follow-up care in patients with inflammatory bowel disease in Brazil.

BACKGROUND: COVID-19 has affected the entire world. We aimed to determine the impact of COVID-19 containment measures on the daily life and follow up of patients with inflammatory bowel disease (IBD). METHODS: During May 2020, we evaluated 179 (79.6%) patients with Crohn's disease (CD) and 46 (20.4%) with ulcerative colitis (UC) by telephone, using a structured questionnaire to gather information on social impact and IBD follow up. RESULTS: Some kind of social distancing measure was reported by 95.6% of our patients, self-quarantine (64.9%) being the most frequent. Depressive mood was the most prevalent social impact (80.2%), followed by anxiety/fear of death (58.2%), insomnia (51.4%), daily activity impairment (48%), sexual dysfunction (46.2%), and productivity impairment (44%). The results were similar when we compared patients with active disease to those in remission and patients with UC to those with CD. Analysis of IBD follow up showed that 83.1% of all patients missed an IBD medical appointment, 45.5% of the patients missed laboratory tests, 41.3% missed the national flu vaccination program, 31.3% missed any radiologic exam, 17.3% missed colonoscopy, and 16.9% failed to obtain biologic therapy prescriptions. Biologics were discontinued by 28.4% of the patients. UC patients had higher rates of missed vaccination than CD patients (56.5% vs. 37.4%, P=0.02) and more failures to obtain a biologic prescription (28.3% vs. 14.0%, P=0.02). CONCLUSIONS: Our study reveals alarming social impacts and declining follow-up care for IBD patients during the COVID-19 outbreak. These findings may have implications for disease control in the near future.

The impact of laparoscopic surgery on the symptoms and wellbeing of patients with deep infiltrating endometriosis and bowel involvement.

BACKGROUND: The purpose of this study was to evaluate the symptoms and wellbeing of patients who underwent laparoscopic colorectal resection for deep endometriosis infiltrating the rectum and/or colon in a single reference center. METHODS: We conducted a cross-sectional survey based on a structured questionnaire. All patients underwent laparoscopic discoid resection, segmental resection or shaving for deep endometriosis in a single reference center between October 2014 and October 2019. The following topics were addressed: symptoms related to endometriosis, fertility, disease recurrence and quality of life. The Institutional Review Board approved the study and signed informed consent was required before enrollment. RESULTS: A total of 77 of 160 (48.1%) subjects agreed to answer the questionnaire and were enrolled in the study. The mean age was 36.4 years (range, 24-54 years), and 45.5% of the patients had previously undergone surgery for deep endometriosis. Complete resolution of abdominal pain was observed in 48.1% of subjects after surgery. Pelvic pain was rated on a scale of 0 (no pain) to 10 (worst pain) before and after the procedure. In this evaluation, mean pain scores were reduced after surgery (9.21 ± 1.53 × 3.99 ± 3.14; p < .001). Other positive aspects reported by interviewees were increased willingness to perform daily activities (66.2%), increased physical activity (70.1%), better work performance (72.7%), improved dyspareunia (77.9%) and increased sexual activity (71.4%). Some negative aspects reported after surgery were straining at stool (35.1%), nocturia (24.7%), liquid-feces incontinence (13%), mild urinary incontinence (13%), urinary urgency (11.7%) and flatus incontinence (7.8%). Regarding pregnancy, 59% of patients tried to conceive after surgery, and the success rate was 28.2% (46.2% spontaneous and 53.8% after in vitro fertilization or insemination). CONCLUSIONS: Laparoscopic surgery was associated with pain reduction and improved general wellbeing in patients diagnosed with deep endometriosis and bowel involvement.

Increased HLA-G Expression in Tissue-Infiltrating Cells in Inflammatory Bowel Diseases.

BACKGROUND: Since HLA-G is an immune checkpoint molecule and since Crohn's disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension. METHODS: HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA. RESULTS: HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P < 0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P = 0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P = 0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P < 0.0001) than in controls, but no difference was observed between diseases. CONCLUSIONS: Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.

ANEMIA AND IRON DEFICIENCY IN INFLAMMATORY BOWEL DISEASE PATIENTS IN A REFERRAL CENTER IN BRAZIL: PREVALENCE AND RISK FACTORS.

BACKGROUND: Data regarding the prevalence of anemia in inflammatory bowel disease (IBD) patients are scarce in Brazil. Anemia and iron deficiency anemia have been known to cause significant functional impairment, lower quality of life, and higher morbidity and mortality and may be correlated with an impact on the cost of treatment. OBJECTIVE: The aim of this study was to estimate the prevalence and risk factors for anemia and iron deficiency anemia in patients with IBD in a tertiary IBD unit in Southeast Brazil. METHODS: We conducted an Institutional Review Board-approved retrospective analysis of an adult IBD cohort (IBD Unit, Ribeirão Preto Medical School, University of São Paulo, Brazil) consisting of 579 patients between January 2014 and July 2018. Clinicoepidemiological data, hemoglobin measurements and serum ferritin were extracted from electronic medical records. Anemia prevalence was calculated among ulcerative colitis (UC) and Crohn's disease (CD) phenotypes. Risk factors for anemia were also calculated. RESULTS: A total of 529 (91%) patients had complete blood counts available in their medical records. Only 35.5% of IBD patients were fully screened for anemia. The prevalence of anemia in IBD patients was 24.6% (29.1% in CD and 19.1% in UC, P=0.008). The anemia was moderate to severe in 16.9% (19.8% in CD and 11.4% in UC, P=0.34). The prevalence of iron deficiency was 52.3% (53.6% in CD and 51.2% in UC, P=0.95). Anemia of chronic disease was present in 14.1% of IBD patients. A total of 53.8% of patients with anemia were in clinical remission. CD was associated with an increased prevalence of anemia (P=0.008; OR=1.76; CI 95% =1.16-2.66) compared to UC. The penetrant disease phenotype in CD was associated with a lower risk of anemia (P<0.0001; OR=0.25; CI 95% =0.14-0.43). Active disease compared to the disease in clinical remission was associated with an increased risk of anemia (P=0.0003; OR=2.61; CI 95% =1.56-4.36) in CD. The presence of anemia was less frequent in patients with CD who underwent surgical bowel resection compared to those who did not undergo surgery (P<0.0001; OR=0.24; CI 95% =0.14-0.40). No differences in anemia prevalence were observed regarding CD localization, age at diagnosis, UC extension or biological therapy (P>0.05). CONCLUSION: Despite the low levels of full screening, anemia and iron deficiency anemia were common manifestations of IBD. CD was associated with an increased risk of anemia, especially with active disease. In addition, patients with CD who underwent surgical bowel resection and penetrant disease phenotype in CD were associated with lower risk of anemia.

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.

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.