Paul E. Wise

Serrated Lesions of the Colorectum: Review and Recommendations From an Expert Panel

Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid >5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.

Health-related quality of life after different types of solid organ transplantation.

ObjectiveTo describe functional health and health-related quality of life (QOL) before and after transplantation; to compare and contrast outcomes among liver, heart, lung, and kidney transplant patients, and compare these outcomes with selected norms; and to explore whether physiologic performance, demographics, and other clinical variables are predictors of posttransplantation overall subjective QOL. Summary Background DataThere is increasing demand for outcomes analysis, including health-related QOL, after medical and surgical interventions. Because of the high cost, interest in transplantation outcomes is particularly intense. With technical surgical experience and improved immunosuppression, survival after solid organ transplantation has matured to acceptable levels. More sensitive measures of outcomes are necessary to evaluate further developments in clinical transplantation, including data on objective functional outcome and subjective QOL. MethodsThe Karnofsky Performance Status was assessed objectively for patients before transplantation and up to 4 years after transplantation, and scores were compared by repeated measures analysis of variance. Subjective evaluation of QOL over time was obtained using the Short Form-36 (SF-36) and the Psychosocial Adjustment to Illness Scale (PAIS). These data were analyzed using multivariate and univariate analysis of variance. A summary model of health-related QOL was tested by path analysis. ResultsTools were administered to 100 liver, 94 heart, 112 kidney, and 65 lung transplant patients. Mean age at transplantation was 48 years; 36% of recipients were female. The Karnofsky Performance Status before transplantation was 37±1 for lung, 38±2 for heart, 53±3 for liver, and 75±1 for kidney recipients. After transplantation, the scores improved to 67±1 at 3 months, 77±1 at 6 months, 82±1 at 12 months, 86±1 at 24 months, 84±2 at 36 months, and 83±3 at 48 months. When patients were stratified by initial performance score as disabled or able, both groups merged in terms of performance by 6 months after liver and heart transplantation; kidney transplant patients maintained their stratification 2 years after transplantation. The SF-36 physical and mental component scales improved after transplantation. The PAIS score improved globally. Path analysis demonstrated a direct effect on the posttransplant Karnofsky score by time after transplantation and diabetes, with trends evident for education and preoperative serum creatinine level. Although neither time after transplantation nor diabetes was directly predictive of a composite QOL score that incorporated all 15 subjective domains, recent Karnofsky score and education level were directly predictive of the QOL composite score. ConclusionsDifferent types of transplant patients have a different health-related QOL before transplantation. Performance improved after transplantation for all four types of transplants, but the trajectories were not the same. Subjective QOL measured by the SF-36 and the PAIS also improved after transplantation. Path analysis shows the important predictors of health-related QOL. These data provide clearly defined and widely useful QOL outcome benchmarks for different types of solid organ transplants.

Use of Endoscopic Ultrasound to Guide Combination Medical and Surgical Therapy for Patients with Crohn's Perianal Fistulas

Background: This study was performed to assess if using endoscopic ultrasound (EUS) to assess and guide combination medical and surgical therapy during fistula healing will lead to a high rate of durable fistula closure and a low or absent incidence of perianal abscess formation in patients with Crohns perianal fistulas. Methods: This is a retrospective analysis of 21 patients who presented with a symptomatic Crohns perianal fistula. Patients were enrolled in a clinical practice protocol of serial EUS exams. All patients underwent a baseline rectal EUS and were placed on maximal medical treatment with 6‐mercaptopurine (6‐MP) or azathioprine, Cipro, and infliximab (5 mg/kg at 0, 2, and 6 wk and then every 8 wk). Patients were also assessed at baseline by a colorectal surgeon who was aware of the EUS findings. Seton placement and incision and drainage were performed when appropriate. Serial EUS examinations were performed, and the findings were used to guide therapy (i.e., the presence of fistula healing on EUS was used to guide seton removal, discontinuation of infliximab, and Cipro). Results: In the 21 patients enrolled, the median duration of active perianal symptoms was 9 wks (1‐36). 10 patients (48%) had previous perianal surgery and 5 (24%) had received infliximab previously. The fistulas treated included 8 trans‐sphincteric, 2 superficial, 3 recto‐vaginal, and 7 with multiple and horseshoe fistulas. 13 patients (62%) had associated abscesses at presentation. Eighteen of 21 patients (86%) had complete cessation of drainage initially. Median time to cessation of drainage was 10.6 weeks (range, 4‐32 wk). Sixteen of 21 patients (76%) maintained long‐term cessation of drainage. The median length of follow‐up was 68 weeks (range, 35‐101 wk). No abscess developed during treatment in any patient. EUS evidence of persistent fistula activity was seen in 10 patients (48%). Of the 11 patients (52%) in whom EUS showed no persistent fistula activity, 7 (64%) have maintained fistula closure off of infliximab and Cipro. Median duration from last infliximab infusion was 47 weeks (range, 20‐80 wk). The remaining 4 patients continued infliximab to maintain remission of their luminal disease. Only 1 patient with a horseshoe fistula showed complete healing on EUS. Conclusion: In conclusion, using EUS to guide therapy for Crohns perianal fistulas with infliximab, an immunosuppressive, and an antibiotic is associated with a high short and long‐term fistula response rate. EUS may identify a subset of patients who can discontinue infliximab without recurrence of fistula drainage.

Effective treatment of biliary cystadenoma.

Objective:Evaluate experience over 15 years with treatment of this lesion. Summary Background Data:Biliary cystadenoma, a benign hepatic tumor arising from Von Meyenberg complexes, usually present as septated intrahepatic cystic lesions. Methods:Data were collected concurrently and retrospectively on patients identified from hospital medical records reviewed for pertinent International Classification of Diseases, Ninth Revision, Clinical Modification and CPT codes, pathology logs, and from operative case logs. Pathology specimens were rereviewed to confirm the diagnosis of biliary cystadenoma or biliary cystadenocarcinoma by 2 GI pathologists. Results:From October 1989 to April 2004 at our institution, 19 (18F:1M) patients had pathologically confirmed biliary cystadenomas, including one with a biliary cystadenocarcinoma. The mean age was 48 ± 15 years at initial evaluation. Complaints included abdominal pain in 74%, abdominal distension in 26%, and nausea/vomiting in 11%. Only 1 patient presented with an incidental finding. Symptoms had been present for 3 ± 5 years, with 1 to 4 different surgeons and many other physicians involved in the diagnosis or treatment prior to definitive ablation. Eight patients had undergone 20 previous treatments, including multiple percutaneous aspirations in 4 and 11 operative procedures. CT or US was diagnostic in 95%, with internal septations present in the hepatic cysts. Definitive operative intervention consisted of hepatic resection in 12 patients, enucleation in 6 patients, and fenestration and complete fulguration in 1 patient. There were no perioperative deaths. No recurrences were observed after definitive therapy, with follow-up of 4 ± 4 years. Conclusions:Biliary cystadenoma must be recognized and treated differently than most hepatic cysts. There remains a need for education about the imaging findings for biliary cystadenoma to reduce the demonstrated delay in appropriate treatment. Traditional treatment of simple cysts such as aspiration, drainage, and marsupialization results in near universal recurrence and occasional malignant degeneration. This experience demonstrates effective options include total ablation by standard hepatic resection and cyst enucleation.

The Successful Use of Adalimumab to Treat Active Crohn's Disease of an Ileoanal Pouch During Pregnancy

The use of immunosuppressive medications during pregnancy in patients with Crohn’s disease is controversial. However, most clinicians would agree that both the unborn baby and the mother will do better if the mother’s inflammatory bowel disease (IBD) can be controlled. Studies have shown that patients with active Crohn’s disease are more likely to experience preterm labor and have babies that are small for gestational age [1]. Currently, the most potent agent approved for Crohn’s disease is infliximab. This is a chimeric anti– tumor necrosis factor-alpha (TNF-α) antibody. Recently, adalimumab (Humira), a fully humanized anti–TNF-α antibody, was approved for the treatment of rheumatoid arthritis (RA) [2–5]. Preliminary studies have demonstrated efficacy in patients with Crohn’s disease, including those who have had a reaction to or lost their response to infliximab because of the development of antibodies to the murine component of this agent [6, 7]. The safety of adalimumab in pregnancy is unknown. There has only been 1 previous report of the use of adalimumab during pregnancy [8]. Herein, we report the first use of adalimumab during pregnancy to treat severe Crohn’s disease of the ileoanal pouch.

Identification of Individuals at Risk for Lynch Syndrome Using Targeted Evaluations and Genetic Testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer Joint Practice Guideline

Identifying individuals who have Lynch syndrome (LS) involves a complex diagnostic work up that includes taking a detailed family history and a combination of various genetic and immunohistochemical tests. The National Society of Genetic Counselors (NSGC) and the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC) have come together to publish this clinical practice testing guideline for the evaluation of LS. The purpose of this practice guideline is to provide guidance and a testing algorithm for LS as well as recommendations on when to offer testing. This guideline does not replace a consultation with a genetics professional. This guideline includes explanations in support of this and a summary of background data. While this guideline is not intended to serve as a review of LS, it includes a discussion of background information on LS, and cites a number of key publications which should be reviewed for a more in-depth understanding of LS. These guidelines are intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses and other healthcare providers who evaluate patients for LS.

A Randomized Prospective Trial of Endoscopic Ultrasound to Guide Combination Medical and Surgical Treatment for Crohn's Perianal Fistulas

AIMS:To prospectively determine if rectal endoscopic ultrasound (EUS) can guide combination medical and surgical therapy and improve outcomes for patients with perianal fistulizing Crohns disease.METHODS:Ten patients with perianal Crohns disease were prospectively enrolled in a randomized prospective pilot study. The patients were randomized to either the EUS cohort or the control group. All patients underwent a rectal EUS to delineate fistula anatomy followed by an examination under anesthesia by a colorectal surgeon with seton placement and/or incision and drainage, as indicated. The surgeon was blinded to the initial EUS results of patients in the control group. Medical treatment was maximized with 6-mercaptopurine (1.0–1.5 mg/kg) or azathioprine (2.0–2.5 mg/kg), ciprofloxacin (1,000 mg a day) or metronidazole (1,500 mg a day), and infliximab (5 mg/kg at 0, 2, and 6 wk and then every 8 wk). For patients in the control group, additional interventions (seton removal and repeat surgery) were at the discretion of the surgeon (without EUS guidance). Patients in the EUS cohort had EUS performed at weeks 22 and 38, with additional surgical interventions based on EUS findings. The primary end point was complete cessation of drainage at week 54. All patients had a repeat EUS performed at week 54 to determine the fistula status on EUS (secondary end point). The need for additional surgery was defined as a treatment failure.RESULTS:Ten patients were enrolled in the study. One of 5 (20%) in the control group and 4 of 5 (80%) in the EUS group had complete cessation of drainage. From the control group, 3 patients failed due to repeat surgery (2 for persistent/recurrent fistula and 1 for abscess), and 1 had a persistent drainage at week 54. In the EUS cohort, 1 patient had a recurrent abscess after his seton fell out prematurely.In the EUS cohort, the median time to cessation of drainage was 99 days, and the time to EUS evidence of fistula inactivity was 229 days.CONCLUSION:This pilot study suggests that using EUS to guide combination medical and surgical therapy for perianal fistulizing Crohns disease improves the outcomes.

Implementing screening for Lynch syndrome among patients with newly diagnosed colorectal cancer: summary of a public health/clinical collaborative meeting

Lynch syndrome is the most common cause of inherited colorectal cancer, accounting for approximately 3% of all colorectal cancer cases in the United States. In 2009, an evidence-based review process conducted by the independent Evaluation of Genomic Applications in Practice and Prevention Working Group resulted in a recommendation to offer genetic testing for Lynch syndrome to all individuals with newly diagnosed colorectal cancer, with the intent of reducing morbidity and mortality in family members. To explore issues surrounding implementation of this recommendation, the Centers for Disease Control and Prevention convened a multidisciplinary working group meeting in September 2010. This article reviews background information regarding screening for Lynch syndrome and summarizes existing clinical paradigms, potential implementation strategies, and conclusions which emerged from the meeting. It was recognized that widespread implementation will present substantial challenges, and additional data from pilot studies will be needed. However, evidence of feasibility and population health benefits and the advantages of considering a public health approach were acknowledged. Lynch syndrome can potentially serve as a model to facilitate the development and implementation of population-level programs for evidence-based genomic medicine applications involving follow-up testing of at-risk relatives. Such endeavors will require multilevel and multidisciplinary approaches building on collaborative public health and clinical partnerships.Genet Med 2012:14(1):152–162

Carcinoid tumors are 15 times more common in patients with Crohn's disease.

Background: The coexistence of intestinal neoplasms with Crohns disease (CD) has been reported, but the evidence of an increased risk of carcinoid tumor with Crohns disease has been mixed. We present 4 patients with CD with associated carcinoid tumor. Methods: The charts of 111 patients with CD who had undergone resection between June 2001 and March 2005 were reviewed. The number of incidental carcinoid tumors in patients who underwent an appendectomy was used as a control. Results: Four cases of carcinoid tumor discovered in patients at resection for CD were identified. None had metastatic disease or carcinoid syndrome. These included 1 cecal (1 mm), 2 appendiceal (3 and 7mm), and 1 transverse colon (7 mm) carcinoid tumors. None of the carcinoid tumors were identified in regions of active Crohns disease. The incidence of carcinoid tumor in patients with Crohns disease was 4 of 111 (3.6%). In comparison, 3 of 1199 patients (0.25%) who had appendectomies were identified as having appendiceal carcinoid tumor. Crohns disease was associated with an increased incidence of carcinoid tumor; OR 14.9 (95% CI 2.5–102.5), P < 0.0001. Conclusions: There was a significantly increased incidence of carcinoid tumor in our Crohns patients compared to the control patients. None of the carcinoid tumors developed in areas of Crohns disease. This suggests that the development of carcinoid tumors may be secondary to distant proinflammatory mediators, rather than a local inflammatory effect from adjacent Crohns disease. Patients with CD may be at increased risk of developing a carcinoid tumor.

Proteomic profiling of mucosal and submucosal colonic tissues yields protein signatures that differentiate the inflammatory colitides

Background: Differentiating ulcerative colitis (UC) from Crohns colitis (CC) can be difficult and may lead to inaccurate diagnoses in up to 30% of inflammatory bowel disease (IBD) patients. Much of the diagnostic uncertainty arises from the overlap of clinical and histologic features. Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) permits a histology‐directed cellular protein analysis of tissues. As a pilot study, we evaluated the ability of histology‐directed MALDI‐MS to determine the proteomic patterns for potential differences between CC and UC specimens. Methods: Mucosal and submucosal layers of CC and UC colon resection samples were analyzed after histologic assessment. To determine whether MALDI‐MS would distinguish inflammation, the uninflamed (n = 21) versus inflamed submucosa (n = 22) were compared in UC and the uninflamed (n = 17) versus inflamed submucosa (n = 20) in CC. To determine whether there were proteomic differences between the colitides, the uninflamed UC submucosa (n = 21) was compared versus the uninflamed CC submucosa (n = 17), the inflamed UC submucosa (n = 22) was compared versus the inflamed CC submucosa (n = 20), and inflamed UC mucosa versus inflamed CC mucosa. Pairwise statistics comparisons of the subsets were performed. Results: Pairwise comparative analyses of the clinical groups allowed identifying subsets of features important for classification. Comparison of inflamed versus uninflamed CC submucosa showed two significant peaks: m/z 6445 (P = 0.0003) and 12692 (P = 0.003). In the case of inflamed versus uninflamed UC submucosa, several significant differentiating peaks were found, but classification was worse. Comparisons of the proteomic spectra of inflamed submucosa between UC and CC identified two discrete significant peaks: m/z 8773 (P = 0.006) and 9245 (P = 0.0009). Comparisons of the proteomic spectra of uninflamed submucosa between UC and CC identified three discrete significant peaks: m/z 2778 (P = 0.005), 9232 (P = 0.005), and 9519 (P = 0.005). No significantly different features were found between UC and CC inflamed mucosa. Conclusions: MALDI‐MS was able to distinguish CC and UC specimens while profiling the colonic submucosa. Further analyses and protein identification of the differential protein peaks may aid in accurately diagnosing IBD and developing appropriate personalized therapies. (Inflamm Bowel Dis 2011;)