Bowel Preparation Improves the Accuracy of Transvaginal Ultrasound in the Diagnosis of Rectosigmoid Deep Infiltrating Endometriosis: A Prospective Study.

STUDY OBJECTIVE: To compare the accuracy of transvaginal ultrasound (TVUS) with and without bowel preparation (BP) to detect and describe intestinal nodules of deep infiltrating endometriosis (DIE) with laparoscopic findings. DESIGN: A prospective study of paired data (Canadian Task Force classification II.1). SETTING: A tertiary university hospital from November 2014 to November 2015. PATIENTS: A cohort of women awaiting surgery for endometriosis. INTERVENTIONS: The wall of the rectum and the lower sigmoid colon of the patients were evaluated by 2 TVUSs: the first ultrasound was performed without previous BP, and the second was done after a 3-day low-residue diet and two 250-mL enemas 12 hours and 3 hours before TVUS. MEASUREMENTS AND MAIN RESULTS: The presence or absence of rectosigmoid nodules visualized by TVUS with and without BP was compared with laparoscopic results. Forty patients with a mean age of 36.8 ± 5.0 years were included in the study. By comparing the surgical findings histologically confirmed (the presence or absence of bowel nodules and localization) with those of the 2 TVUSs with and without BP, the sensitivity, specificity, and Cohen kappa were 100%, 96%, and 0.95 and 73%, 88%, and 0.61, respectively. Laparoscopy showed that up to 37.5% of patients (15/40) presented bowel involvement. Variables were clearly more evaluable with than without BP. CONCLUSION: TVUS with BP has a higher accuracy than TVUS without BP. BP allows and facilitates the detection of more rectal nodules of DIE in patients with suspected endometriosis and surgical criteria.

Initial Accuracy of and Learning Curve for Transvaginal Ultrasound with Bowel Preparation for Deep Endometriosis in a US Tertiary Care Center.

STUDY OBJECTIVE: To evaluate the diagnostic accuracy and learning curve of a sonographic mapping protocol for deep endometriosis (DE). DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Tertiary referral center in the United States. PATIENTS: 117 consecutive patients who presented to our gynecology clinic with complaints of significant noncyclic pelvic pain of at least 6 months' duration, and/or clinical findings concerning for deep endometriosis and who were referred for transvaginal ultrasound with bowel preparation. INTERVENTIONS: Patients underwent transvaginal ultrasound with bowel-preparation (TVUS-BP) performed by a single radiologist. Findings suspicious for DE were reported and correlated with surgical and histopathological findings. The duration of the examination and number of cases required to achieve proficiency were calculated for positive, equivocal, and negative findings. MEASUREMENTS AND MAIN RESULTS: Among 117 patients (median age, 35 years; range, 19-54 years) referred for TVUS-BP, 113 had complete examinations. Fifty-seven of these 113 patients underwent surgical exploration within 1 year, and DE was identified surgically in 23 of them. DE of the rectosigmoid colon and/or rectovaginal septum was detected with a sensitivity of 94% (95% confidence interval [CI], 70%-100%) and specificity of 100% (95% CI, 91%-100%). DE of the retrocervical region and/or uterosacral ligaments was detected with a sensitivity of 86% (95% CI, 65%-97%) and specificity of 94% (95% CI, 81%-99%). Proficiency, defined by a flattening of the learning curve, was achieved after 70 to 75 scans. The mean duration of the examination was 42 ± 4 minutes initially, but declined to 15 ± 4 minutes once proficiency was achieved. Cases of equivocal or minimal disease demonstrated the greatest decline in examination duration. CONCLUSION: A newly applied TVUS-BP protocol for detection of pelvic DE is highly accurate and required only a modest learning curve to achieve procedural proficiency in a US tertiary referral center where physicians interpret but typically do not perform TVUS exams. Overcoming diagnostic uncertainty regarding minimal or equivocal disease appeared to be an important factor in the initial learning curve. With adequate training, TVUS-BP may be adapted as a primary diagnostic tool for detecting pelvic DE.

Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue.

The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health.

Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon.

OBJECTIVE: Opioid therapy is associated with altered secretion and motility of the gut. The relative contribution of decreased secretion to the development of opioid-induced constipation remains unknown. MATERIALS AND METHODS: Twenty-five healthy males were treated with oxycodone for 5 d in a placebo-controlled, randomised cross-over design. Gastrointestinal adverse effects were assessed with validated questionnaires (bowel function index and gastrointestinal symptom rating scale). Rectosigmoid mucosal biopsies were taken at baseline and on day 5 during both treatments and mounted in Ussing chambers. Electrogenic ion transport parameters (short circuit current (SCC) and slope conductance) were measured after addition of secretagogues (prostaglandin E2 (PGE2) (6 µm), theophylline (400 µm)), and an inhibitor (ouabain (200 µm)). Additionally, morphine (50 µm) was added to investigate the direct opioid effect on colonic mucosa. RESULTS: Questionnaires showed pronounced bowel symptoms, including constipation during oxycodone treatment (eight-fold increase in bowel function index score from day 1 to day 5 (p < 0.001) while no significant change occurred during placebo treatment (p = 0.47). Basal SCC and slope conductance did not differ between treatments (all p > 0.05) and application with PGE2, theophylline, and ouabain yielded comparable results on all examinations (all p > 0.05). Morphine application consistently did not evoke a change in ion transport. CONCLUSION: Compared to placebo, epithelial electrogenic ion transport is not altered in mucosal biopsies from the rectosigmoid colon following 5-d oxycodone treatment. The secretory mechanisms in isolated mucosa appear to play a negligible role in the development of opioid-induced constipation.

A case report of sevelamer-associated recto-sigmoid ulcers.

BACKGROUND: Optimal phosphorous control is an important aspect of the care of patients with end-stage renal disease, and phosphate binders are usually needed. CASE PRESENTATION: A 74-year-old woman with end-stage renal disease on maintenance hemodialysis presented to the emergency room with abdominal discomfort, rectal pain, and blood-tinged stools. Initial concern was for a rectal carcinoma, based on the symptoms and imaging in initial computerized tomography of the abdomen showing rectal wall thickening, and her clinical presentation. She had been treated with the phosphate binder sevelamer for two months. In this case report, we explore the unique features of sevelamer-associated recto-sigmoid ulcers which led to her symptoms. CONCLUSION: Sevelamer is widely used in chronic kidney disease and end-stage renal disease patients with hyperphosphatemia. It is a crosslinked polymeric amine that binds phosphates and bile acids; it is not systemically absorbed. To the authors' knowledge, this is the first reported case of recto-sigmoid ulcers associated with use of this phosphate binder. Nephrologists, pathologists, and gastroenterology sub-specialists should be aware of this recently-reported entity in patients on sevelamer with suggestive symptoms, as this medication is widely used in renal patients.

Defecation into clothing without forewarning and mean radiation dose to bowel and anal-sphincter among gynecological cancer survivors.

BACKGROUND: To analyze the relationship between mean radiation dose to the bowels and the anal-sphincter and occurrence of 'defecation into clothing without forewarning', a specific and serious fecal incontinence symptom after gynecological radiotherapy. Additional potential risk factors associated with the symptom are explored. MATERIAL AND METHODS: Data were collected for 519 eligible gynecological cancer survivors, treated with pelvic radiotherapy, with a median follow-up of 5.8 years, using a study-specific questionnaire and medical records. Correlations between defecation into clothing without forewarning and mean dose to organs at risk; the anal-sphincter region, the rectum, the sigmoid and the small intestines were investigated, also taking other risk factors into account. RESULTS: Twelve percent reported having had the symptom at least once in the preceding six months. Mean doses >50 Gy to the anal-sphincter region, the rectum, the sigmoid and the small intestines were related to the occurrence of the symptom. Significantly associated risk factors were deliveries with high birth weight, heart failure and lactose and/or gluten intolerance. After adjusting for these factors, mean doses >50 Gy to the anal-sphincter region, the sigmoid and the small intestines remained related to the occurrence of the symptom. CONCLUSION: Mean doses to the bowels and anal-sphincter region are related to the risk of defecation into clothing without forewarning in long-term gynecological cancer survivors treated with pelvic radiotherapy. Further radiobiological modeling may distinguish which organ(s) contribute most to development of the symptom.

Sigmoid-vaginal fistula during bevacizumab treatment diagnosed by fistulography.

WHAT IS KNOWN AND OBJECTIVE: There have been several reports describing rectovaginal fistula development after bevacizumab treatment, and these fistulas were diagnosed by CT scan or colonoscopy. We report a case of sigmoid-vaginal fistula diagnosed by fistulography. CASE DESCRIPTION: The case is a 53-year-old woman who was treated for chronic myelogenous leukaemia and gynaecological cancers 8 years previously. At 52 years of age, she was diagnosed with colon cancer and had a partial colectomy performed. One year after surgery, colon cancer recurred, and she was treated with anticancer agents, including bevacizumab. During chemotherapy, she complained of a foul smelling discharge from the vagina. Fistulography revealed a sigmoid-vaginal fistula. WHAT IS NEW AND CONCLUSION: This is the first report of vaginal fistulography performed on a patient who was treated with bevacizumab. Fistulography may be useful for detecting sigmoid-vaginal fistula.

Prostaglandin ethanolamides attenuate damage in a human explant colitis model.

Endocannabinoids are protective in animal colitis models. As endocannabinoids also form novel prostaglandin ethanolamides (prostamides) via COX-2, we investigated the effects of prostamides and other COX-2 mediators on tissue damage in an ex vivo human mucosal explant colitis model. Healthy human colonic mucosae were incubated with pro-inflammatory cytokines TNF-α and IL-1ß to elicit colitis-like tissue damage. The PGF-ethanolamide analogue, bimatoprost decreased colitis scores which were reversed by a prostamide-specific antagonist AGN 211334, but not the FP receptor antagonist AL-8810. PGF-ethanolamide and PGE-ethanolamide also reduced cytokine-evoked epithelial damage. Anandamide was protective in the explant colitis model; however COX-2 inhibition did not alter its effects, associated with a lack of COX-2 induction in explant mucosal tissue. These findings support an anti-inflammatory role for prostamides and endocannabinoids in the human colon.

[Biological aspects of choice of the intestinal segment for the cystoplasty].

Contractile activity of the iliac and sigmoid intestines versus detrusor activity, reabsorption and secretory activity of the iliac and sigmoid intestinal mucosa in contact with urine were studied in 30 rats. It was found that isolated segments of the iliac and sigmoid intestines have spontaneous contractile activity (stronger in the iliac intestine) while bladder segment contracted only in response to electric stimulation. A contraction-stimulating effect of acetylcholine and a relaxing effect of noradrenaline in experiments with the iliac intestine were close to their effects on the detrusor. The sigmoid intestine responded weaker to the above mediators. The iliac mucosa actively reabsorbed urinary urea, creatinin, glucose causing elevation of their concentrations in blood as well as K, Na, Ca, CI, P and secreted protein in urine leading to hypoproteinemia. The sigmoid mucosa showed weaker metabolic activity. The results of the study demonstrate importance of consideration of biological properties of different intestinal regions for choice of a cystoplasty method after cystectomy.

[Food poisoning by cucurbitacines]. / Lebensmittelvergiftung durch Cucurbitacine.

MEDICAL HISTORY AND CLINICAL PRESENTATION: A 66-year-old female patient was admitted to the emergency department following bitter zucchini ingestion. Clinical symptoms were tachycardia, hypotension, somnolence, diarrhea, hematochezia as well as exsiccosis, nausea and emesis. EXAMINATION AND DIAGNOSIS: Laboratory results showed leukocytosis and signs of exsiccosis. Ultrasound revealed thickening of the sigmoid colon wall, interpretable as acute colitis. Poisoning with cucurbitacin containing zucchini was diagnosed. THERAPY: The patient improved after intravenous fluid administration. Hemorrhagic colitis with diarrhea was self limiting. After 2 days, the patient was able to eat again. CONCLUSION: Acute food poisoning due to cucurbitacin - containing pumpkin is rare but can occur in small gardening units in association with higher outside temperatures. Cucurbitacin poisoning has to be taken into account for differential diagnosis in food poisoning. Bitter taste is essential to diagnose cucurbitacin intoxications.

A noteworthy treatment of metastatic small-cell lung cancer with afatinib, followed by subsequent development of rare metastatic lesions in the ascending and sigmoid colon.

BACKGROUND: Small-cell lung cancer (SCLC) represents a group of highly fatal diseases with a tendency toward fast growth, early metastasis, and easy development of chemotherapy resistance. In the past 30 years, few advances have been made in the systemic treatment of SCLC, and cisplatin/etoposide has remained the standard of care for limited-stage SCLC and, in combination with radiotherapy, extensive-stage SCLC. The preferred metastatic sites of SCLC include the brain, liver, adrenal glands, bone, and bone marrow. However, bowel metastasis caused by SCLC is extremely rarely proved in patients while they are still alive (although autopsy studies suggest that silent metastases to the bowel are more common), and the standard treatment for bowel metastasis has never been reported. The mean time between the identification of gastrointestinal metastasis and mortality in patients with lung cancer is 100.6 days, with a range of 21-145 days. CASE: We report the case of a patient with extensive SCLC (including brain metastasis), in which exon 19 deletion of epidermal growth factor receptor (EGFR) was detected. She initially refused chemotherapy and cranial radiotherapy and instead only agreed to oral target therapy. The second-generation EGFR-tyrosine kinase inhibitor (TKI), afatinib, was administered to the patient, and partial remission, including smaller metastatic brain tumors, was noted. Even though the subsequent development of rare metastatic lesions in the ascending and sigmoid colon was proved by colonoscopic biopsies, the prolonged overall survival (400 days) without standard treatment was marked in this case. CONCLUSION: The patient with extensive metastasis of SCLC did not receive standard systemic chemotherapy. Instead, she initially received second-generation EGFR-TKI afatinib alone and later on whole brain radiotherapy as well (3 weeks before she expired). The prolonged overall survival of 400 days was marked and is worthy of sharing and further investigation.

Role of serotonin in systemic impairment of motor function of the digestive tract.

We studied the role of serotonin in systemic impairment of motor function of the digestive tract. Administration of a nitric oxide donor methylene blue into the pre-fundal portion of the stomach and application of a loose ligature to the terminal part of the sigmoid colon were performed after pretreatment with serotonin. Serotonin had a stabilizing effect on esophageal antiperistalsis under conditions of dynamic obstruction of the sigmoid colon.

The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon.

Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s.c.) twice weekly for 4 weeks in a single-arm, phase 1b/2a study. Within sigmoid mucosa, global transcriptomic analyses revealed 248 modulated genes (false discovery rate<0.05) including many type I interferon (IFN)-stimulated genes. MGN1703 increased the frequencies of cells exhibiting MX1 (P=0.001) and ISG15 (P=0.014) protein expression. No changes were observed in neutrophil infiltration (myeloperoxidase; P=0.97). No systematic effect on fecal microbiota structure was observed (analysis of similarity Global R=-0.105; P=0.929). TLR9 expression at baseline was inversely proportional to the change in integrated HIV DNA during MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.

P2 purinoceptor antagonists inhibit the non-adrenergic, non-cholinergic relaxation of the human colon in vitro.

Neurotransmitters released by myenteric neurons regulate movements of intestinal smooth muscles. There has been little pharmacological evidence for a role of purinergic mechanisms in the non-adrenergic, non-cholinergic (NANC) relaxation of the human large intestine. We used P(2) purinoceptor antagonists to assess whether such receptors are involved in the NANC relaxation of the circular muscle of the human sigmoid colon. It was also investigated whether the guanylate cyclase enzyme mediates the NANC response. Human colonic circular strips were tested in organ bath experiments with isotonic recording. NANC, non-nitrergic relaxations induced by electrical field stimulation (1 and 10 Hz, in the presence of atropine, guanethidine, and 100 microM N(G)-nitro-L-arginine [L-NOARG]) were strongly inhibited by a combination of the P(2) purinoceptor antagonists pyridoxal-phosphate-6-azophenyl-2',4'-sulfonic acid (PPADS) (50 microM) and suramin (100 microM). PPADS plus suramin was ineffective in the absence of L-NOARG. L-NOARG alone significantly reduced the NANC relaxation to electrical stimulation. PPADS plus suramin strongly inhibited the relaxation in response to exogenous alpha,beta-methylene ATP. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (3 microM) inhibited the NANC relaxation, but did not add to its reduction by L-NOARG. L-NOARG was still slightly effective in the presence of ODQ. Vasoactive intestinal polypeptide tachyphylaxis failed to influence the non-nitrergic NANC relaxation. It is concluded that nitric oxide (NO) and ATP co-mediate, in a non-additive manner, the NANC relaxation. NO probably acts through the guanylate cyclase, though a small fraction of its effect might be mediated by other mechanisms. Activators of the guanylate cyclase other than NO do not seem to participate in the NANC relaxation.

Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon.

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.

Effects of basic fibroblast growth factor and phenytoin on healing of abdominal wall fascia and colonic anastomoses.

The aim of this study was to investigate the effects of basic fibroblast growth factor (bFGF) and phenytoin on wound healing in rats compromised by methylprednisone. This study was conducted in four groups consisting of 20 male Wistar rats. Rats in groups 2, 3, and 4 had a daily injection of methylprednisolone 5 mg/kg/day for 15 days. Laparotomy and sigmoid transsection were performed on day 15. In the postoperative period, rats in group 1 received no medication, group 2 received methylprednisolone 5 mg/kg/day intramuscularly, group 3 received bFGF 5 microg/kg on days 1-3 subcutaneously, and group 4 received phenytoin 40 mg/kg/day intraperitoneally. bFGF and phenytoin had a positive effect on tensile strength, hydroxyproline content, and wound healing parameters in abdominal wall fascia. In colonic anastomosis, phenytoin corrected all parameters, but bFGF had no effect.