Diagnosis and Management of Functional Pouch Disorders: A Systematic Review.

BACKGROUND: Functional disorders impart significant morbidity in patients with inflammatory bowel disease who undergo restorative proctocolectomy. OBJECTIVE: This systematic review aimed to summarize the management strategies for various functional disorders of the pouch. DATA SOURCES: A database search of PubMed was conducted to identify relevant clinical studies assessing the management of various functional disorders in patients who underwent restorative proctocolectomy. STUDY SELECTION: Published clinical studies investigating a functional disorder of the pouch in patients who previously underwent a colectomy with ileal pouch-anal anastomosis. INTERVENTIONS: Restorative proctocolectomy was completed in patients with inflammatory bowel disease or other indications such as a diagnosis of familial adenomatous polyposis. MAIN OUTCOME MEASURES: The primary outcomes described in this review include the prevalence of functional disorders of the pouch in patients undergoing restorative proctocolectomy and the relevant management strategies. RESULTS: Ten clinical studies were identified using the predetermined search terms and screened for relevancy to patients with inflammatory bowel disease who previously underwent colectomy with ileal pouch-anal anastomosis. A qualitative summary was developed on the basis of data from these studies and from current guidelines developed for the management of inflammatory bowel disease. LIMITATIONS: This systematic review is limited by the small number and low quality of the clinical studies included as well as the nonquantitative summary of the findings. CONCLUSIONS: Functional disorders of the pouch are likely underdiagnosed. Although a source of significant morbidity, these diseases require additional clinical studies to better elucidate effective management strategies.

Tissue-specific signatures of activating PIK3CA and RAS mutations in carcinosarcomas of gynecologic origin.

OBJECTIVES: Gynecologic carcinosarcoma is an aggressive malignancy that requires more effective treatment approaches. However, therapeutic implications regarding the specific gynecologic site of origin and the admixture of carcinomatous and sarcomatous elements that define this tumor remain uncertain. Therefore, broad genotyping was performed to identify tissue-specific somatic mutational profiles that may help direct targeted therapies in this complex neoplasia. METHODS: Genotyping was conducted on primary gynecologic carcinosarcomas arising from various disease sites (uterus, ovary, fallopian tube, vagina) and within isolated histological subcomponents. Nucleic acids extracted from diagnostic tissue were used in a genotyping platform that simultaneously queried >120 common mutations across 14 cancer genes. Mutational status was correlated with clinical variables using logistic regression and Kaplan-Meier survival estimates. RESULTS: Cancer gene mutations were identified in 46% of the 52 patient cohort and include TP53 (23%), PIK3CA (19%), KRAS (15%), CTNNB1 (4%) and NRAS (2%). Mutation in a single gene was observed in 31% of patient samples, while synchronous mutations involving 2 and 3 genes were noted in 13% and 2% of samples, respectively. Comparative evaluation of the carcinomatous and sarcomatous elements within a tumor demonstrated a similar mutation signature. Mutations in PIK3CA, KRAS and NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and TP53 mutations with decreased survival in the uterine subset. CONCLUSION: While carcinosarcomas across gynecologic disease sites are histologically similar, therapeutically relevant mutations in the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways predominated in carcinosarcomas arising in the uterus.