The New Proactive Approach and Precision Medicine in Crohn's Disease.

The proactive approach to Crohn's disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.

Preoperative exposure to anti-tumor necrosis factor therapy in ulcerative colitis patients undergoing ileal pouch-anal anastomosis (IPAA) is not associated with histological fibrosis: A case control study.

BACKGROUND: We sought to determine whether preoperative exposure to anti-TNF therapy affects objective histological measures of fibrosis in the colorectum. METHODS: Ulcerative colitis (UC) patients who received infliximab as maintenance therapy pre IPAA surgery were identified and compared to anti-TNF-naïve matched controls by age, sex, BMI, disease duration, albumin levels, and post-operative leak outcome. Hematoxylin and eosin- (H&E) and trichrome-stained slides from the most distal, well-oriented, full-thickness section of colorectum from each patient's total colectomy specimen were evaluated. Blinded histopathological assessment of the degree of fibrosis was performed using a semi-quantitative pictorial scale. RESULTS: Histological fibrosis in 65 patients from the therapy group was compared to 65 patients from the matched control group. There were no statistically significant differences in the degree of fibrosis observed in any of the bowel layers. In the lamina propria, 29% of the control group and 28% of the treatment group had fibrosis scores ≥3. Fibrosis scores were higher in the submucosa, with both groups having 66% of patients showing scores ≥3. Similarly, in the region above the muscularis propria, 77% of the control group and 80% of the treatment group had fibrosis scores ≥3. In the subserosa, fibrosis scores were lower, with 25% of the control group and 32% of the treatment group having fibrosis scores ≥3. CONCLUSION: Resection specimens from UC patients treated with maintenance anti-TNF therapy who underwent IPAA surgery showed no significant differences in the degree of histologic fibrosis in any of the bowel layers compared to a matched control group.

Would Marjolin see it coming? Two unusual cases of squamous cell carcinoma.

INTRODUCTION: Cutaneous squamous cell carcinoma (SCC) is a common skin cancer, second in incidence only to basal cell carcinoma (BCC). The incidence of SCC increases significantly with age; thus, it is rarely diagnosed in young patients. In this paper, we present two cases of young patients who presented clinically with purulent lesions that were later diagnosed as large primary SCCs. MATERIALS AND METHODS: A review of the medical records of two patients who were admitted to the department of plastic surgery with a final clinical diagnosis of cutaneous SCC was conducted. Information of the review included history, physical examination, laboratory tests, imaging studies and histology. A literature review was also conducted and discussed. RESULTS: Two female patients under the age of 45 presented with large, purulent lesions that were initially clinically suggestive of an infectious etiology. The lesions were surgically treated by incision and drainage without sending tissue samples to pathology. Biopsies of the lesions were performed to obtain a tissue diagnosis due to recurrence approximately one year after the initial treatment. Histological evaluation revealed well differentiated squamous cell carcinomas. Surgical intervention with wide excision with adjuvant chemotherapy was recommended based on biopsy and CT scan results. DISCUSSION: Aggressive behavior of SCC in young patients is uncommon. The patients in this report were diagnosed only one year after the first sign of the lesion. One patient was first diagnosed with an abscess, and the other with necrotizing fasciitis. The delayed diagnosis of SCC in these two patients is a potential contributing factor to the aggressiveness of the tumors. Therefore, it is imperative to perform skin biopsies of chronic or persistent purulent lesions to rule out malignancies including Marjolin's ulcer. CONCLUSION: Aggressive SCC should be suspected in cases of persistent and relapsing purulent lesions in all patients.

Anti-TNF-α therapies for the treatment of Crohn's disease: the past, present and future.

INTRODUCTION: Anti-TNF-α therapy is a novel approach that has transformed the way moderate-to-severe Crohn's disease (CD) is treated and has significantly improved clinical outcomes of patients with enhanced remission induction and maintenance efficacies. As a result, anti-TNF-α agents have become the primary cost driver in the treatment of CD, as the frequency of hospitalizations and surgical interventions have been drastically reduced. AREAS COVERED: In the review, the authors cover current anti-TNF-α treatments for CD including efficacy, mechanisms of action, pharmacokinetics and safety. In addition, the authors discuss future anti-TNF-α agents currently in the development pipeline including biosimilars, golimumab, oral AVX-470, TNF-α-kinoid vaccine, and non-biologic HMPL-004. EXPERT OPINION: While new therapeutics are in the pipeline like anti-integrin and anti-interleukin therapeutics, anti-TNF-α therapy remains at the forefront of CD treatment due to its long-term efficacy and safety profiles. The next horizon for new anti-TNF-α agents is biosimilars, which offer comparable safety and effectiveness to the originator molecules. Biosimilars promise to expand accessibility to anti-TNF-α therapy while significantly reducing the cost burden to patients and healthcare systems.