Suresh Pola

Feasibility of endoscopic assessment and treating to target to achieve mucosal healing in ulcerative colitis.

Background:Mucosal healing (MH) as a treatment target for ulcerative colitis is of growing interest because it is associated with improved clinical outcomes. However, the feasibility and probability of reaching MH in clinical practice is unknown. We therefore evaluated the feasibility of “treating to target” according to endoscopic findings to reach MH. Methods:All endoscopic outcomes of patients with ulcerative colitis followed in a single inflammatory bowel disease unit from 2011 to 2012 were reviewed and subsequent therapeutic management. Cumulative incidence of MH and histologic healing (HH) were estimated using a Kaplan–Meier method. Results:A total of 60 patients underwent at least 2 consecutive endoscopic assessments, of whom 45 and 48 patients had endoscopic and histologic evidence of active disease, respectively. After a median follow-up of 76 weeks, 27 of 45 (60%) patients with endoscopic disease activity at baseline achieved MH and 24 (50%) of 48 patients with histologic disease activity at baseline had HH. The cumulative probabilities of MH were 26%, 52%, and 70% at 26, 52, and 76 weeks, respectively. The cumulative probabilities of HH at weeks 26, 52, and 76 from the time of initial procedure were 19%, 41%, and 57%, respectively. Any adjustment in medical therapy in case of persistent endoscopic activity was associated with both MH and HH. Conclusions:Repeated assessment of endoscopic disease activity with adjustment of medical therapy to the target of MH is feasible in clinical practice in patients with ulcerative colitis, and seems to be of benefit.

Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disease of the colon; as many as 25% of patients with this disease require hospitalization. The goals of hospitalization are to assess disease severity, exclude infection, administer rapidly acting and highly effective medication regimens, and determine response. During hospitalization, patients should be given venous thromboembolism prophylaxis and monitored for the development of toxic megacolon. Patients who do not respond to intravenous corticosteroids should be considered for rescue therapy with infliximab or cyclosporine. Patients who are refractory to medical therapies or who develop toxic megacolon should be evaluated promptly for colectomy. Patients who do respond to medical therapies should be discharged on an appropriate maintenance regimen when they meet discharge criteria. We review practical evidence-based management principles and propose a day-by-day algorithm for managing patients hospitalized for ulcerative colitis.

Successful Use of Infliximab in the Treatment of Corticosteroid Dependent Collagenous Colitis

Successful Use of Infliximab in the Treatment of Corticosteroid Dependent Collagenous Colitis

Validated gene expression biomarker analysis for biopsy-based clinical trials in ulcerative colitis.

Accurate and reproducible measurement of expression of pro‐inflammatory cytokines in colonic biopsies from patients with ulcerative colitis (UC) is essential for proof‐of‐concept and mechanism‐of‐action studies. Few studies have rigorously established the number of biopsies required for accurate and reproducible biomarker measurements.

An Overview of Magnetic Resonance Enterography for Crohn’s Disease

Magnetic resonance enterography (MRE) is a relatively new imaging modality that has shown promise for diagnosing, staging, and monitoring Crohn’s disease (CD) and its complications while avoiding exposure to ionizing radiation. In addition to clinical implications, MRE has the potential to be used as an objective measure of disease activity for clinical trials. We provide the rationale for MRE, indications for its use, and an overview of the typical procedure and common findings for institutions who want to begin or refine the use of MRE for CD.

Transanal Endoscopic Surgical Proctectomy for Proctitis Case Series Report: Diversion, Radiation, Ulcerative Colitis, and Crohn’s Disease

Abstract: Background: With recent trends in natural orifice surgery, there has been a rising interest in the evolution of transanal endoscopic surgery (TES) and transanal access platforms. Transanal endoluminal removal of rectal masses has matured into transanal endoscopic surgical resection of the rectum for benign and malignant disease. The purpose of this study is to evaluate the surgical outcomes of TES completion proctectomy in patients with proctitis in a retained rectum. Methods: This is a retrospective case series report. Patient demographics and peri-operative outcome variables were recorded. Results: TES proctectomy was successfully performed in 6 patients using a disposable transanal access platform. The patients ages ranged from 22 – 74 years, 4 women and 2 men, BMI ranged from 22 – 51 kg/m2. The indication for surgery was proctitis in a retained rectum: diversion (n=1), radiation (n=1), ulcerative colitis (n=2), and Crohns disease (n=2). Four applications of TES proctectomy were employed: TES completion proctectomy (n=2), TES assisted single incision abdominal perineal resection (n=1), TES assisted laparoscopic restorative proctectomy with colo-anal anastomosis (n=1), and TES assisted laparoscopic restorative total proctocolectomy with ileal pouch anal anastomosis (n=1). The operative time for TES completion proctectomy ranged from 140 – 238 minutes (n=4). The operative time for TES restorative proctectomy was longer at 446 min and 557 min (n=2). The hospital length of stay for both TES completion and restorative proctectomy ranged from 2 – 5 days (n=5). Complications included 1 urinary tract infection, 1 chronic draining perineal sinus tract, and 1 perineal wound dehiscence requiring re-operation. All six patients are doing well at the time of follow up (range 3 – 19 months). Conclusions: TES completion proctectomy alone or in combination with laparoscopic abdominal surgery is a safe and effective method to perform proctectomy and restorative proctectomy in this small case series of patients with proctitis in a retained rectum due to diversion, radiation, ulcerative colitis, and Crohns disease.

Validation of gene expression biomarker analysis for biopsy-based clinical trials in Crohn’s disease

Background:The ability to measure the expression of proinflammatory cytokines from intestinal biopsies in patients with Crohns disease in an accurate and reproducible way is critical for proof-of-concept and mechanism-of-action trials; however, the number of biopsies from a segment of the ileum or colon required to yield reproducible results has not been rigorously evaluated. We examined intestinal biopsies from patients with Crohns disease to validate methods for detecting changes in inflammatory gene expression. Methods:To evaluate the reproducibility of gene expression measurements, intestinal biopsies were obtained from designated segments from 6 healthy controls, 6 patients with active Crohns disease, and 6 patients with inactive Crohns disease. Disease activity was based on the simple endoscopic score for Crohns disease. Expression of 7 proinflammatory genes was measured from each biopsy using quantitative polymerase chain reaction. Using a linear mixed effects model, the power to detect transcriptional changes corresponding to active and inactive Crohns disease was calculated. Results:Total simple endoscopic score for Crohns disease score corresponds with expression of most inflammatory biomarkers. For most genes, 2 to 5 biopsies are needed to reduce sampling error to <25% for most genes. To measure changes in mRNA expression corresponding to active versus inactive Crohns disease, 1 to 2 intestinal biopsies from 3 patients before and after treatment are needed to yield power of at least 80%. Conclusions:Measuring proinflammatory gene expression from mucosal biopsies from patients with Crohns disease is practicable and provides objective biomarkers that can be used in proof-of-concept and mechanism-of-action trials to assess response to therapy.

Non-cirrhotic portal hypertension due to 6-mercaptopurine use for Crohn's disease.

A 12-year-old boy was diagnosed with Crohn’s disease (CD) of the colon and started on 50 mg (1.3 mg/kg) of 6-mercaptopurine (6-MP) daily. His thiopurine S-methyltransferase enzyme activity was normal. The 6-MP dose was subsequently increased to 1.9 mg/kg for persistent symptoms. One year later, the patient’s 6-thioguanine (6TGN) concentration had risen to 434 pmol/8 9 10 red blood cells (RBCs; normal range 230–400) and the 6-methyl-mercaptopurine concentration was 4,699 pmol/ 8 9 10 RBCs. Three years after the patient was started on 6-MP, the leukocyte count had dropped to 3.8 9 1,000/ mm with a platelet count of 118 9 1,000/mm and normal liver aminotransferases. Therapy with 6-MP was discontinued, but the platelet and leukocyte count remained low. A bone marrow biopsy was normal. Since the patient was asymptomatic, he was monitored off medications. Two years later, the patient developed abdominal pain and weight loss. Esophagogastroduodenoscopy revealed esophageal varices and portal hypertensive gastropathy. Colonoscopy revealed severe CD with deep ulcers throughout the colon. Pathology showed severely active chronic colitis with granulomas, but immunostaining for cytomegalovirus (CMV) was negative. Magnetic resonance cholangiopancreatography showed no biliary dilatation. A transjugular liver biopsy revealed features of nodular regenerative hyperplasia with portal fibrosis (Fig. 1).

Su1174 The Use of Magnetic Resonance Enterography for Diagnosis and Monitoring of Inflammatory Bowel Disease in Clinical Practice

end points were time to surgery and time to tx failure (defined as either need for surgery, biologic therapy stopped or switched due to lack of efficacy or adverse events).Specific MRE findings ; 1. penetrating complications e.g fistulae, 2. Small bowel stenosis (SBS) +/dilatation, 3. Small bowel wall thickening (SBWT) and 4. Relative contrast enhancement (RCE) were then correlated to primary and secondary end points. RESULTS: In total,353 patients were commenced on aTNFtx for CD(182 adalimumab and 171 infliximab).Of these 54 patients had an MRE prior to commencing aTNFtx(23 infliximab;31 adalimumab).The median time from MRE to aTNFtx was 66.2 days (+/58.4). 13/54(24.1%) had surgery within the following year due to tx failure.The proportion of patients with SBS on MRE was significantly greater in those who went on to have surgery within 1 year;10/13 (76.9%) vs 3/ 41(7.3%)respectively (chi-square p,0.001).The frequency of penetrating complications, SBWT and RCE was not significantly different in the group who required early surgery.Time to surgery was significantly shorter in patients with SBS on MRE (log rank p=0.001).34 patients were defined as tx responders vs 20 who experienced tx failure. In a multivariate analysis using cox proportional hazards model, the MRE variables independently associated with time to tx failure were SBS (p ,0.001, hazard ratio 17.9, 95% CI 4.5-71.4) and penetrating complications (p,0.027, hazard ratio 14.5 95% CI 1.4-155.3) . CONCLUSION: The presence of SBS on MRE can help predict need for early surgery and is associated with tx failure in patients who commence aTNFtx. These findings demonstrate the utility of MRE in planning tx and suggest that aTNFtx may be more effective when commenced early in disease course, prior to onset of fibrostenotic or penetrating complications.

An Unusual Finding on Screening Colonoscopy—Pancreatic Cancer

Pancreatic cancer is the second most common tumor of the gastrointestinal tract and the fourth leading cause of cancerrelated mortality in the Western world. In the USA, there are more than 28,000 new cases of pancreatic cancer diagnosed each year, and 37,000 deaths result from this disease annually [1, 2]. Despite advances in imaging modalities, pancreatic cancer is frequently diagnosed at an advanced stage, precluding the possibility of curative treatment. The location of the tumor within the pancreas (head, body, or tail) is a major predictor of clinical presentation and stage [3]. Unlike tumors affecting the pancreatic head, neoplasms of the tail of the pancreas often do not cause early symptoms, therefore extra-pancreatic extension or metastasis is common at the time of diagnosis [4]. While there are no significant histological differences between adenocarcinoma in the pancreatic head, body, or tail, survival amongst patients with adenocarcinoma of the tail is substantially lower [5]. We present a case of a pancreatic tail adenocarcinoma identified during a routine screening colonoscopy. An asymptomatic 73-year-old Mexican man was referred by his primary care physician for his first screening colonoscopy. He denied changes in bowel habits, blood in his stool, abdominal pain, or weight loss. His past medical history included type 2 diabetes mellitus, hypertension, and hyperlipidemia. He was a nonsmoker, reported occasional alcohol consumption, and denied illicit drug use. Family history was relevant for laryngeal cancer in his father and endometrial cancer in his daughter. Electrolyte panel and liver function tests performed approximately 3 months prior to the colonoscopy were remarkable only for a glucose of 182 mg/dL. The most recent complete blood count had been performed 2 years prior and had been notable for a mild normocytic anemia (hemoglobin 12.7 g/dL). The colonoscopy revealed two slightly ulcerated mucosal irregularities measuring 3 and 7 mm in diameter in the transverse colon (Fig. 1). These lesions were not associated with colitis or any visible mass lesion. Biopsies were taken and histopathologic evaluation revealed atypical neoplastic glands invading the submucosa surrounded by desmoplastic stroma, suggestive of invasive adenocarcinoma (Fig. 2). A CT scan of the abdomen and pelvis was subsequently performed. This demonstrated a 3.4×2.9-cm low attenuation lesion in the pancreatic tail extending anteriorly into the transverse mesocolon toward the distal transverse colon. Multiple low attenuation ill-defined hepatic lesions measuring up to 8.2 cm as well as mildly enlarged retroperitoneal lymph nodes and mesenteric infiltration were also seen, suggestive of metastatic disease. A repeat colonoscopy was performed in order to obtain additional pathologic specimens for immunohistochemical analysis to definitively identify the origin of the malignant tissue. The second colonoscopy revealed a 10×10-mm ulcerated area, again without any associated mass. Biopsy specimens confirmed invasive moderately differentiated adenocarcinoma, strongly reactive with cytokeratin (CK) 7 antibody, and only focally and weakly reactive with CK 20 antibody. These findings are most consistent with a primary pancreatic rather than colonic adenocarcinoma [6]. Diana L. Franco and Suresh Pola are the co-first authors. D. L. Franco (*) : S. Pola (*) UC San Diego Health System, 9500 Gilman Dr, San Diego, CA 92093-0063, USA e-mail: dfranco@ucsd.edu e-mail: spola@ucsd.edu