Fábio Vieira Teixeira

The onset of psoriasis during the treatment of inflammatory bowel diseases with infliximab: should biological therapy be suspended?

CONTEXT Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. OBJECTIVE To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. METHODS A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. RESULTS Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohns disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. CONCLUSION As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

Risk factors for complications after ileocolonic resection for Crohn’s disease with a major focus on the impact of preoperative immunosuppressive and biologic therapy: A retrospective international multicentre study

Background Author note: TY, AS, YS, FVT and PGK designed the study. All authors did data collection and gave scientific contribution to the study design and discussion. TY, AS and PGK drafted the article. All authors read and approved the final version of the manuscript. In the era of biologic agents, risk factors for complications following resection for Crohn’s disease have not been fully identified. In particular, the association of preoperative use of immunosuppressive and biologic agents with the incidence of complications after resection remains to be elucidated. Aim This retrospective multicentre study aimed to identify risk factors for complications after ileocolonic resection for Crohn’s disease, with a major focus on the impact of preoperative immunosuppressive and biologic therapy. Methods A total of 231 consecutive patients who underwent ileocolonic resections for active Crohn’s disease in seven inflammatory bowel disease referral centres from three countries (Japan, Brazil and Italy) were included. The following variables were investigated as potential risk factors: age at surgery, gender, behaviour of Crohn’s disease (perforating vs. non-perforating disease), smoking, preoperative use (within eight weeks before surgery) of steroids, immunosuppressants and biologic agents, previous resection, blood transfusion, surgical procedure (open vs. laparoscopic approach), and type of anastomosis (side-to-side vs. end-to-end). Postoperative complications occurring within 30 days after surgery were recorded. Results The rates of overall complications, intra-abdominal sepsis, and anastomotic leak were 24%, 12% and 8%, respectively. Neither immunosuppressive nor biologic therapy prior to surgery was significantly associated with the incidence of overall complications, intra-abdominal sepsis or anastomotic leak. In multivariate analysis, blood transfusion, perforating disease and previous resection were significant risk factors for overall complications (odds ratio [OR] 3.02, 95% confidence interval [CI] 1.21–7.52; P = 0.02), intra-abdominal sepsis (OR 2.67, 95% CI 1.04–6.86; P = 0.04) and anastomotic leak (OR 2.87, 95% CI 1.01–8.18; P = 0.048), respectively. Conclusions Blood transfusion, perforating disease and previous resection were significant risk factors for overall complications, intra-abdominal sepsis and anastomotic leak after ileocolonic resection for Crohn’s disease, respectively. Preoperative immunosuppressive or biologic therapy did not increase the risk of postoperative complications.

Recommendations on the use of biosimilars by the Brazilian Society of Rheumatology, Brazilian Society of Dermatology, Brazilian Federation of Gastroenterology and Brazilian Study Group on Inflammatory Bowel Disease—Focus on clinical evaluation of monoclonal antibodies and fusion proteins used in the treatment of autoimmune diseases

The Brazilian Societies of Rheumatology (SBR) and Dermatology (SBD), the Brazilian Federation of Gastroenterology (FBG) and the Brazilian Study Group on Inflammatory Bowel Disease (GEDIIB) gathered a group of their respective specialists on the topic of interest to discuss the most relevant issues regarding the clinical use of biosimilar medicines in Brazil. The main aim of that meeting was to prepare a document with recommendations to guide medical specialists and to help the national regulatory and policy-making agencies as concerns the authorization for marketing biosimilars used in autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohns disease, juvenile idiopathic arthritis and ulcerative colitis. In addition to considerations on the typical differences between innovator medicines and biosimilars, the specialists established a set of seven recommendations on regulatory advances related to clinical studies, indication extrapolation, nomenclature, interchangeability, automatic substitution and pharmacovigilance.

Enhancing release of peptide yy after near-total proctocolectomy: jejunal pouch vs. ileal pouch-distal rectal anastomosis

Reconstructing the enteric tract after near-total proctocolectomy by interposing a jejunal pouch between the distal ileum and the distal rectum slows small intestinal transit and decreases the number of stools per day compared to a conventional ileal pouch-distal rectal reconstruction. Our hypothesis was that the jejunal pouch operation brings about these results by protecting the ability of the ileal mucosa to secrete peptide YY, thus augmenting the hormonal ileal brake on small intestinal transit and decreasing the stool frequency. In five jejunal pouch dogs and five ileal pouch dogs, more than 6 months after the operation, serum peptide YY concentrations were determined before and at 30-minute intervals for 180 minutes after a standard meal. Fasting serum concentrations of peptide YY, measured by radioimmunoassay, were greater in jejunal pouch dogs (mean ± SEM, 1340 ±143 pg/ml) than in ileal pouch dogs (804 ±52 pg/ml; P <0.01). Postprandial peptide YY concentrations in jejunal pouch dogs were also greater at 30 minutes (jejunal pouch = 1524 ±131 pg/ml, ileal pouch = 913 ±67 pg/ml; P = 0.01) and 60 minutes after the meal (jejunal pouch = 1723 ±250 pg/ml, ileal pouch = 1001 ±70 pg/ml; P = 0.05) and peaked sooner (jejunal pouch = 81 ±17 minutes, ileal pouch = 147 ±12 minutes; P = 0.01). We concluded that the jejunal pouch operation results in greater ileal fasting and postprandial secretion of peptide YY than the ileal pouch operation. The greater release may account, in part, for the slower small bowel transit and decreased number of stools after the jejunal pouch operation.

BIOSIMILARS IN INFLAMMATORY BOWEL DISEASES: an important moment for Brazilian gastroenterologists

Biosimilars are not generic drugs. These are more complex medications than small molecules, with identical chemical structures of monoclonal antibodies that lost their patency over time. Besides identical to the original product at the end, the process of achieving its final forms differs from the one used in the reference products. These differences in the formulation process can alter final outcomes such as safety and efficacy of the drugs. Recently, a biosimilar of Infliximab was approved in some countries, even to the management of inflammatory bowel diseases. However, this decision was based on studies performed in rheumatologic conditions such as rheumatoid arthritis and ankylosing spondylitis. Extrapolation of the indications from rheumatologic conditions was done for Crohns disease and ulcerative colitis based on these studies. In this article, the authors explain possible different mechanisms in the pathogenesis between rheumatologic conditions and inflammatory bowel diseases, that can lead to different actions of the medications in different diseases. The authors also alert the gastroenterological community for the problem of extrapolation of indications, and explain in full details the reasons for being care with the use of biosimilars in inflammatory bowel diseases without specific data from trials performed in this scenario.

In vivo assessment of intratumoral aspirin injection to treat hepatic tumors

AIM To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (10(4) cells/rabbit) via supra-umbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirin-treated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nodules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) and at 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both, P < 0.005). CONCLUSION Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treatment administration.

Fitobezoar em íleo terminal: uma causa rara de obstrução intestinal

Universidade Estadual Paulista Julio de Mesquita Filho, Departamento de Cirurgia e Ortopedia, Faculdade de Medicina de Botucatu, Botucatu, Anexo Verde 3 Andar, Rubiao Junior, CEP 18618970, SP, Brasil

The jejunal pouch as a rectal substitute after proctocolectomy

Our hypothesis was that a jejunal pouch used as a rectal substitute after proctocolectomy would slow enteric transit, delay defecation, and decrease stool frequency compared to an ileal pouch so used. Twelve dogs underwent proctocolectomy; six had a jejunal pouch-distal rectal anastomosis and six had an ileal pouch-distal rectal anastomosis. After recovery, postprandial mouth-to-anus transit was slower in jejunal pouch dogs (253 ±18 minutes [mean ± SEM]) than in ileal pouch dogs (112 ±7.9 minutes; P <0.05). Moreover, jejunal pouch dogs passed only 4.1 ± 0.3 stools during the 12 hours after eating, whereas ileal pouch dogs passed 6.3 ± 0.9 stools (P <0.05). The mean frequency of proximal ileal pacesetter potentials after feeding was less in jejunal pouch dogs (12 ± 0.4 cycles/min) than in ileal pouch dogs (16 ± 0.3 counts/min; P = 0.01), and jejunal pouches had more action potentials (jejunal = 82% ±4.3% of pacesetter potentials had action potentials, ileal = 61% ±3.0%; P <0.05). In contrast, gastric emptying and pouch motility, emptying, mucosal integrity, and bacteriologie and histologic properties were similar in the two groups of dogs. We concluded that the jejunal pouch operation slowed enteric transit, delayed defecation, and decreased postprandial stooling compared to the ileal pouch operation.

Factors affecting the incidence of early endoscopic recurrence after ileocolonic resection for Crohn's disease: a multicentre observational study

Early endoscopic recurrence is frequently observed in patients following resection for Crohns disease (CD). However, factors affecting the incidence of an early postoperative endoscopic recurrence (EPER) have not been fully determined. The aim of this study was to evaluate risk factors for EPER after ileocolonic resection for CD.

Management of psoriatic lesions associated with anti-TNF therapy in patients with IBD

Univ State Sao Paulo UNESP, Sch Med Sci, Dept Surg, Div Coloproctol, BR-17516707 Sao Paulo, Brazil