ABSTRACT
PURPOSE: Radiotherapy is important in managing pelvic cancers. However, radiation enteropathy may occur and can be dose limiting. The gut microbiota may contribute to the pathogenesis of radiation enteropathy. We hypothesized that the microbiome differs between patients with and without radiation enteropathy.Experimental Design: Three cohorts of patients (n = 134) were recruited. The early cohort (n = 32) was followed sequentially up to 12 months post-radiotherapy to assess early radiation enteropathy. Linear mixed models were used to assess microbiota dynamics. The late cohort (n = 87) was assessed cross-sectionally to assess late radiation enteropathy. The colonoscopy cohort compared the intestinal mucosa microenvironment in patients with radiation enteropathy (cases, n = 9) with healthy controls (controls, n = 6). Fecal samples were obtained from all cohorts. In the colonoscopy cohort, intestinal mucosa samples were taken. Metataxonomics (16S rRNA gene) and imputed metataxonomics (Piphillin) were used to characterize the microbiome. Clinician- and patient-reported outcomes were used for clinical characterization. RESULTS: In the acute cohort, we observed a trend for higher preradiotherapy diversity in patients with no self-reported symptoms (P = 0.09). Dynamically, diversity decreased less over time in patients with rising radiation enteropathy (P = 0.05). A consistent association between low bacterial diversity and late radiation enteropathy was also observed, albeit nonsignificantly. Higher counts of Clostridium IV, Roseburia, and Phascolarctobacterium significantly associated with radiation enteropathy. Homeostatic intestinal mucosa cytokines related to microbiota regulation and intestinal wall maintenance were significantly reduced in radiation enteropathy [IL7 (P = 0.05), IL12/IL23p40 (P = 0.03), IL15 (P = 0.05), and IL16 (P = 0.009)]. IL15 inversely correlated with counts of Roseburia and Propionibacterium. CONCLUSIONS: The microbiota presents opportunities to predict, prevent, or treat radiation enteropathy. We report the largest clinical study to date into associations of the microbiota with acute and late radiation enteropathy. An altered microbiota associates with early and late radiation enteropathy, with clinical implications for risk assessment, prevention, and treatment of radiation-induced side-effects.See related commentary by Lam et al., p. 6280.
Subject(s)
Bacteria/genetics , Gastrointestinal Tract/microbiology , Pelvic Neoplasms/radiotherapy , Radiation Injuries/genetics , Aged , Bacteria/classification , Bacteria/radiation effects , Feces/microbiology , Female , Gastrointestinal Microbiome/radiation effects , Gastrointestinal Tract/pathology , Gastrointestinal Tract/radiation effects , Humans , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Intestinal Mucosa/radiation effects , Male , Middle Aged , Pelvic Neoplasms/complications , Pelvic Neoplasms/microbiology , Pelvic Neoplasms/pathology , RNA, Ribosomal, 16S/genetics , Radiation Exposure/adverse effects , Radiation Injuries/microbiology , Radiation Injuries/pathologyABSTRACT
A 24-year-old woman having two children using an intrauterine contraceptive device was admitted with lower abdominal pain and fever. On clinical and radiographic examination revealed a 7x6 cm multi-loculated cystic mass in the lower abdomen. The differential diagnosis included twisted ovarian cyst, ectopic pregnancy, tubercular tubo-ovarian (TO) mass red degeneration fibroid, diverticular diseases, emphysematous cystitis, pelvic malignancy, and mesenteric cyst. On histologic examination, an actinomycotic TO abscess was found with sulfur granules.
Subject(s)
Actinomycosis/microbiology , Pelvic Neoplasms/microbiology , Actinomycosis/diagnostic imaging , Actinomycosis/drug therapy , Actinomycosis/surgery , Female , Humans , Intrauterine Devices/microbiology , Laparotomy , Pelvic Neoplasms/diagnostic imaging , Pelvic Neoplasms/drug therapy , Pelvic Neoplasms/surgery , Penicillins/therapeutic use , Ultrasonography , Young AdultABSTRACT
Metastatic tissue from an endocervical adenocarcinoma was examined for human papilloma virus (HPV) DNA sequences. Southern blot analysis with 32P-labeled viral probes revealed the presence of about 150 copies of HPV-16 DNA per cellular genome. DNA in situ hybridization of frozen sections with biotinylated probes showed that HPV-16 DNA was exclusively detectable in the nuclei of the malignant epithelial cells and not in the stroma.
Subject(s)
Adenocarcinoma/microbiology , DNA, Viral/analysis , Papillomaviridae/genetics , Pelvic Neoplasms/microbiology , Uterine Cervical Neoplasms/microbiology , Adenocarcinoma/secondary , Adult , Female , Humans , Nucleic Acid Hybridization , Pelvic Neoplasms/secondary , Tumor Virus Infections/microbiologyABSTRACT
Pelvic endometriosis and simian foamy virus infection occurred in a pigtailed macaque. Diffuse omental, peritoneal, and intestinal implantation of endometrium resulted in massive adhesions between adjacent abdominal and pelvic viscera, with formation of a large mass in the right caudal quadrant of the abdomen. Simian foamy virus type 1 was isolated from ectopic endometrium and from the uterine wall but was considered to be merely epiphenomenal.
