Michael V. Chiorean

Correlation of CT Enteroclysis With Surgical Pathology in Crohn's Disease

BACKGROUND:The response to therapy in Crohns disease (CD) depends on the inflammatory or fibrostenotic nature of the underlying pathological process. Standard diagnostic tests cannot reliably distinguish between these two entities. Although CT enteroclysis (CTE) has shown promise in the evaluation of small bowel disorders, its accuracy for the differentiation of CD phenotypes is unknown.AIMS:To determine the accuracy of CTE compared with surgical pathology in patients with CD and to assess the association of CTE variables with inflammatory or fibrostenotic pathological lesions.METHODS:CTE studies from patients who underwent resective bowel surgery for CD were reviewed and compared with the pathological specimens using a standardized scoring system. Patients were excluded if they had incomplete studies, nonresective surgeries, or a diagnosis of malignancy. CTE variables, such as mucosal and mural enhancement, wall thickness, engorgement of vasa recta (comb sign), adenopathy, and the presence and severity of strictures were compared with the pathology results using Mantel-Haenszel χ2, Spearmans rank coefficient, and logistic regression analyses.RESULTS:Of the 54 patients enrolled, 10 were excluded. The remaining patients (61% female, 84% white) underwent 44 surgical interventions generating 47 bowel segments that were included in the analysis. The indications for surgery were: bowel obstruction in 21; perforating disease in 13; and refractory, nonobstructive disease in 15. The accuracy of CTE for inflammatory and fibrostenotic lesions was 76.6% and 78.7% using a four- and three-point grading system, respectively. There was good correlation between CTE and pathology in regards to inflammation (Spearmans r = 0.7, P < 0.0001) and fibrostenosis (Spearmans r = 0.6, P < 0.0001) scores. The pathological inflammation score was significantly associated with the CTE variables mucosal enhancement, wall thickness, comb sign, and adenopathy (Mantel-Haenszel χ2 P values 0.04, 0.04, <0.0001, and 0.016, respectively). The pathological fibrostenosis score was significantly associated with the presence and severity of stenosis on CTE (P = 0.001 and 0.007, respectively). By logistic regression analysis, the strongest association was seen with the comb sign (OR 5.52, P < 0.001) for inflammation and the presence of stenosis (OR 5.87, P = 0.006) for fibrostenosis. There was no interaction between the time interval from CTE to surgery and the strength of these associations.CONCLUSIONS:CTE may reliably differentiate between inflammatory and fibrostenotic lesions and may have an important role in the management of CD. Specific CTE variables correlate with each of these phenotypes and deserve further investigations in prospective studies.

Spiral enteroscopy: prospective U.S. multicenter study in patients with small-bowel disorders

BACKGROUND The performance characteristics of spiral enteroscopy have not been well-described. OBJECTIVE To determine the technical performance, diagnostic and therapeutic yields, and safety of oral spiral enteroscopy in patients with suspected or established small-bowel pathology. DESIGN Prospective, multicenter, cohort study, with centralized database. SETTING Ten U.S. tertiary-care medical centers. PATIENTS This study involved 148 participants, of whom 101 were referred for obscure bleeding. All participants referred for antegrade deep enteroscopy were considered eligible. INTERVENTION Spiral enteroscopy. MAIN OUTCOME MEASUREMENTS Examination duration, depth of insertion, spiral enteroscopy findings, mucosal assessment upon withdrawal, and patient symptom assessment (day 1 and day 7 after the procedure). RESULTS Spiral enteroscopy was successful in 93% of patients, with a median depth of insertion beyond the angle of Treitz of 250 cm (range 10-600 cm). The mean (± standard deviation) total procedure time was 45.0 ± 16.2 minutes for all procedures, and 35.4 minutes for diagnostic procedures. The diagnostic yield was 65%, of which 48% revealed more than one abnormality. The most common findings were angiectasias (61.5%), inflammation (7.5%), and neoplasia (6.8%). Argon plasma coagulation ablation accounted for 64% of therapeutic interventions. LIMITATIONS This was not a randomized, controlled trial of deep enteroscopy modalities. CONCLUSION Spiral enteroscopy appears to be safe and effective for evaluation of the small bowel. The procedure duration, depth of insertion, and diagnostic and therapeutic yields compare favorably with previously published data on other deep enteroscopy techniques such as single-balloon and double-balloon enteroscopy. Comparative studies are warranted.

Comparison of pain and postoperative stress in dogs undergoing natural orifice transluminal endoscopic surgery, laparoscopic, and open oophorectomy

BACKGROUND Few studies are available to compare the potential benefits of natural orifice transluminal endoscopic surgery (NOTES) approaches to traditional surgery. OBJECTIVE To compare complications, surgical stress, and postoperative pain. DESIGN Prospective study in dogs. SETTING Research laboratory. SUBJECTS Thirty dogs. INTERVENTIONS Oophorectomy procedures were performed via NOTES and laparoscopic and traditional open surgery. MAIN OUTCOME MEASUREMENTS Operative time, pain scores, systemic stress parameters (cortisol, glucose), surgical stress markers (interleukin 6, C-reactive protein), 3-day observation. RESULTS Median operative times were 76, 44, and 35 minutes for the NOTES, laparoscopic, and open procedures, respectively, with the NOTES procedure being significantly longer than the other 2 procedures. All ovaries were completely excised, and all the animals survived without complications. The NOTES animals had greater increases in serum cortisol concentrations at 2 hours but no statistically significant differences in glucose concentrations compared with the other groups. Serum interleukin 6 and C-reactive protein concentrations were significantly increased at specific times compared with baseline in the NOTES group, but not in the open or laparoscopic surgery groups. Based on the cumulative pain score and nociceptive thresholds, the animals in the NOTES group demonstrated less evidence of pain. LIMITATIONS Small sample size, limited follow-up. CONCLUSIONS Although the NOTES oophorectomy procedures took approximately twice as long and there may be more evidence of tissue damage as judged by increases in serum cortisol and interleukin 6 concentrations, the dogs in the NOTES group had lower pain scores, especially when compared with animals undergoing open surgery.

Radiologic Investigations Complement and Add Diagnostic Information to Capsule Endoscopy of Small-Bowel Diseases

OBJECTIVE The purpose of our study was to review how commonly performed radiologic examinations compare with capsule endoscopy in the investigation of small-bowel diseases, to analyze the limitations of capsule imaging, and to propose an algorithm for use of specific radiologic examinations to complement wireless capsule endoscopy. CONCLUSION The diagnostic yield of capsule endoscopy is superior to that of radiologic examinations except air double-contrast enteroclysis for mucosal details. Radiologic investigations find new applications in clinical practice by complementing capsule endoscopy to overcome its limitations.

Oophorectomy by natural orifice transluminal endoscopic surgery: feasibility study in dogs

BACKGROUND Natural orifice transluminal endoscopic surgery (NOTES) represents a potentially less-invasive alternative to conventional or laparoscopic surgery. OBJECTIVE Our purpose was to develop a canine oophorectomy model for prospective evaluation of intraoperative complications, surgical stress, and postoperative pain and recovery with NOTES. DESIGN Feasibility study. SETTING Academic preclinical research. PATIENTS Ten healthy female dogs. INTERVENTIONS NOTES procedures were performed through gastric access with an electrocautery snare to resect and retrieve the ovaries. The gastrotomy was closed with prototype T-fasteners. MAIN OUTCOME MEASUREMENTS Operative time; complications; postoperative pain scores, and nociceptive threshold; surgical stress markers (interleukin-6 [IL-6], C-reactive protein); systemic stress parameters (cortisol, glucose); necropsy evaluation at 10 to 14 days. RESULTS The mean operative time was 154 minutes (SD +/- 58 minutes) and no animals died as a result of complications from the procedure. The primary difficulty was incomplete ovarian excision and conversion to an open procedure in 1 dog. Serum glucose concentrations increased after surgery and remained elevated for at least 36 hours. The serum cortisol concentration was transiently increased from baseline at 2 hours after surgery. The serum IL-6 concentration peaked at 2 hours after surgery and returned to the baseline value by 18 hours. The serum C-reactive protein concentration increased significantly from baseline, peaked at 12 hours after surgery, and then slowly declined toward baseline but remained elevated at 72 hours after surgery. Nociceptive threshold measurements indicated increased sensitivity to pain for 2 to 24 hours after surgery. At necropsy, surgical sites were healing uneventfully with no significant damage to surrounding organs, no significant growth on bacterial cultures, and no evidence of peritonitis. LIMITATIONS Small number of animals, single center. CONCLUSIONS The NOTES approach to oophorectomy in dogs appears to be a reasonable alternative to traditional surgery. Attention must be paid to ensure complete excision of the ovaries.

Capsule endoscopy and imaging tests in the elective investigation of small bowel disease

Capsule endoscopy enables high-resolution depiction of small bowel mucosa and has been shown, by several studies, to have a high diagnostic yield in a variety of small bowel diseases. In this review, we critically assess the contributions of capsule endoscopy and imaging tests in common small bowel disorders. Radiological tests that only assess the small bowel mucosa will be less useful in the era of capsule endoscopy.

Risks and Benefits of Colonoscopy in Patients 90 Years or Older, Compared With Younger Patients

BACKGROUND & AIMS Although the numbers of medical procedures performed on extremely elderly patients (90 years or older, nonagenarians) are increasing, there are no data on the performance, diagnostic yield, or safety of colonoscopy for these patients. We compared the performance and safety of diagnostic colonoscopy, as well as lesions detected, in nonagenarians with patients who were 75 to 79 years old. METHODS In a retrospective study, we compared data from 76 extremely elderly patients (90 years or older) with data from 140 very elderly patients (75 to 79 years old, controls), all of whom underwent diagnostic colonoscopy from January 2010 through March 2013 at Virginia Mason Medical Center. All colonoscopies were performed by 15 endoscopists. We compared rates of colonoscopy completion, bowel preparation quality, diagnostic yield, and adverse events. RESULTS In extremely elderly patients, more colonoscopies were performed under general anesthesia, compared with controls (P < .001). When extremely elderly patients underwent colonoscopies with moderate sedation, lower doses of midazolam and fentanyl were given, compared with controls (P < .001). Colonoscopies were completed in a lower proportion of extremely elderly patients (88.2% vs. 99.3% for controls, P < .001), and these patients had a higher incidence of inadequate bowel preparation (29.7% vs. 15.0% for controls, P = .011). Colonoscopies were also associated with cardiopulmonary events in a higher proportion of extremely elderly patients (P = .006) as well as overall adverse events, compared with controls (P = .002). A higher proportion of extremely elderly patients were found to have advanced neoplasia (28.4% vs. 6.4% of controls, P < .001) as well as any neoplasia (P < .001 vs. controls). A greater percentage of extremely elderly patients also had large lesions (P = .002) and malignancies detected by histology (P < .001 vs. controls). Eleven extremely elderly patients (14.9%) were found to have cancer or high-grade dysplasia by colonoscopy. CONCLUSIONS In patients 90 years or older, diagnostic colonoscopy is associated with increased risk for incomplete procedure, inadequate bowel preparation, and adverse events. However, a large proportion of patients are found to have advanced neoplasia and cancer, compared with patients 75 to 79 years old.

Disparities in prevalence, location, and shape characteristics of colorectal neoplasia between South Korean and U.S. patients

BACKGROUND Colon cancer screening is being introduced in many countries, but standard Western screening approaches may not be appropriate for Asian societies if differences in colon cancer epidemiology exist. Comparative analysis of colorectal neoplasia patterns in South Korean and Western subjects has implications for appropriate screening approaches in non-Western societies. METHODS The results of concurrent screening colonoscopies performed in average-risk patients 50 to 69 years old in 2 teaching hospitals, Kyung Hee University Hospital (Seoul, South Korea) and Virginia Mason Medical Center (Seattle, Wash), were compared with respect to prevalence, histologic features, anatomic distribution, and shape characteristics of colorectal neoplasia. RESULTS The U.S. (n = 3460) and South Korean (n = 2193) cohorts were similar with regard to the prevalence of adenomas (28.5% vs 29.8%, respectively, P = .312) and advanced neoplasia (6.4% vs 5.4%, respectively, P = .102), but the proportion of proximal adenomas was greater in the U.S. cohort (62.8% vs 45.9%, P < .001). The prevalence of adenomas and advanced neoplasia was similar in male patients, but there was a greater prevalence of neoplasia (23.5% vs 18.8%, P = .006) and advanced neoplasia (5.1% vs 2.7%, P < .001) in U.S. women than South Korean women. When large (≥10 mm) adenomas were considered, proximal location and nonpolypoid (flat) shape were more common in the U.S. cohort (79.4% vs 37.1%, P = .003 and 43.5% vs 12.3%, P < .001, respectively). The overall prevalence of large flat adenomas in the U.S. cohort was 5 times that of the South Korean cohort (2.6% vs 0.5%, P < .001). Adjustment for sex ratio discrepancies (48.3% men in the U.S. cohort vs 60.8% in the South Korean cohort, P < .001) did not result in any significant changes in the conclusions. CONCLUSION Compared with Westerners, South Koreans have a more distal distribution of adenomas and advanced neoplasia and lower prevalence of large flat adenomas. South Korean women have a lower prevalence of colorectal neoplasia than Western women. Such disparities suggest that Western screening strategies cannot be directly adopted by other countries, but need to be customized by society.

Elevated phospholipase A2 activities in plasma samples from multiple cancers.

Only in recent years have phospholipase A2 enzymes (PLA2s) emerged as cancer targets. In this work, we report the first detection of elevated PLA2 activities in plasma from patients with colorectal, lung, pancreatic, and bladder cancers as compared to healthy controls. Independent sets of clinical plasma samples were obtained from two different sites. The first set was from patients with colorectal cancer (CRC; n = 38) and healthy controls (n = 77). The second set was from patients with lung (n = 95), bladder (n = 31), or pancreatic cancers (n = 38), and healthy controls (n = 79). PLA2 activities were analyzed by a validated quantitative fluorescent assay method and subtype PLA2 activities were defined in the presence of selective inhibitors. The natural PLA2 activity, as well as each subtype of PLA2 activity was elevated in each cancer group as compared to healthy controls. PLA2 activities were increased in late stage vs. early stage cases in CRC. PLA2 activities were not influenced by sex, smoking, alcohol consumption, or body-mass index (BMI). Samples from the two independent sites confirmed the results. Plasma PLA2 activities had approximately 70% specificity and sensitivity to detect cancer. The marker and targeting values of PLA2 activity have been suggested.

Spontaneous regression of colonic lymphoma following infliximab and azathioprine withdrawal in patients with Crohn's disease.

with UC and rare chromosomal abnormalities. Patient 1: A girl with micrognathia, ocular hypertelorism, auricular abnormality, and mental and motor retardation has a karyotype of 46,XX,der(21),t(9;21)(q32;q22.3). She was diagnosed with UC at the age of 6 years. At diagnosis, her pediatric UC activity index was 65 (severe), and disease extent represented pancolitis. She did not respond to steroid treatment and received oral tacrolimus as induction therapy. Despite changing to azathioprine for maintenance therapy, she had 2 exacerbations within 1 year. She underwent colectomy at the age of 7 years. Patient 2: A girl with polyhydramnios, facial dysmorphism, “coat-hanger” appearance of the ribs, bell-shaped thorax, diastasis recti, and mental and motor retardation had paternal uniparental disomy of chromosome 14. She was diagnosed with UC at the age of 2 years 7 months. At diagnosis, her pediatric UC activity index was 65 (severe), and disease extent represented pancolitis. She was steroid dependent and was given azathioprine for maintenance therapy 9 months after the diagnosis. Unfortunately, at the age of 3 years 7 months, she died of acute respiratory distress caused by respiratory syncytial virus during a period of remission. An association between UC and TS has been described. Price reported that the prevalence UC was 1.48% in a series of 135 patients with TS; distinctive findings developed at a young age, and colitis often was severe. Similarly, these 2 patients had early onsets and refractory disease. Recently, genome-wide and candidate gene association studies have identified 47 susceptibility loci for UC. Interestingly, patient 1 has abnormalities of chromosome 9q32 and 21q22 that were included among these 47 loci. To our knowledge, this is the first report of UC associated with either of the rare chromosome abnormalities in our patients.