Eric J. Dozois

Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract

Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.

Diverticulitis: A Progressive Disease?: Do Multiple Recurrences Predict Less Favorable Outcomes?

Introduction:Our understanding of complicated diverticulitis is based on outdated literature. Antecedent episodes of diverticulitis are felt to increase the risk of developing complicated diverticulitis, as well as its subsequent morbidity and mortality. Practice parameters recommend elective resection after 2 episodes of diverticulitis to reduce this morbidity and mortality. Methods:A total of 150 patients with prior episodes of diverticulitis who were hospitalized with complicated diverticulitis were retrospectively analyzed. Statistical analysis was conducted using &khgr;2 and Fisher exact test tests. Results:Patients were separated into 2 groups for analysis: group A = those with 1 or 2 prior diverticulitis episodes (n = 118) versus group B = patients with more than 2 prior episodes (n = 32). Characteristics of the groups were similar for age and preexistent comorbid conditions. The majority of patients presented with pericolonic abscess and inflammatory phlegmon. Perforated diverticulitis occurred more often in group A compared with patients with >2 episodes of diverticulitis. Because of the higher rate of perforation, patients in group A underwent surgical diversion more often than group B patients. No significant differences in operative complications, morbidity, or mortality rates were identified between the groups. Conclusion:Patients with multiple (>2) episodes of diverticulitis are not at increased risk for poor outcomes if they develop complicated diverticulitis. Morbidity and mortality rates are not significantly different between patients with multiple episodes of diverticulitis compared with those with 1 or 2 prior attacks. Reevaluation of the practice of elective resection as a strategy for reducing the mortality and morbidity from complicated diverticulitis is needed.

Complicated Diverticulitis: Is It Time to Rethink the Rules?

Introduction:Much of our knowledge and treatment of complicated diverticulitis (CD) are based on outdated literature reporting mortality rates of 10%. Practice parameters recommend elective resection after 2 episodes of diverticulitis to reduce morbidity and mortality. The aim of this study is to update our understanding of the morbidity, mortality, characteristics, and outcomes of CD. Methods:Three hundred thirty-seven patients hospitalized for CD were retrospectively analyzed. Characteristics and outcomes were determined using chi-squared and Fisher exact tests. Results:Mean age of patients was 65 years. Seventy percent had one or more comorbidities. A total of 46.6% had a history of at least one prior diverticulitis episode, whereas 53.4% presented with CD as their first episode. Overall mortality rate was 6.5% (86.4% associated with perforation, 9.5% anastomotic leak, 4.5% patient managed nonoperatively). A total of 89.5% of the perforation patients who died had no history of diverticulitis. Steroid use was significantly associated with perforation rates as well as mortality (P< 0.001 and P = 0.002). Comorbidities such as diabetes, collagen–vascular disease, and immune system compromise were also highly associated with death (P = 0.006, P = 0.009, and P = 0.003, respectively). Overall morbidity was 41.4%. Older age, gender, steroids, comorbidities, and perforation were significantly associated with morbidity. Conclusion:Today, mortality from CD excluding perforation is reduced compared with past data. This, coupled with the fact that the majority of these patients presented with CD as their first episode, calls into question the current practice of elective resection as a stratagem for reducing mortality. Immunocompromised patients may benefit from early resection. New prospective data is needed to redefine target groups for prophylactic resection.

Safety, Feasibility, and Short-term Outcomes of Laparoscopic Ileal-Pouch-Anal Anastomosis: A Single Institutional Case-Matched Experience

Objective:To compare safety and short-term outcomes of 100 laparoscopic ileal pouch-anal anastomosis (IPAA) versus 200 conventional open IPAA patients. Summary Background Data:Outcomes of laparoscopic IPAA (LAP-IPAA) have been incompletely characterized. Previous reports are characterized by small numbers of patients and rarely include case-matched or randomized trial methodology. This report describes 100 LAP-IPAA patients case matched to 200 open IPAA patients. Methods:Between 1998 and 2004, 100 consecutive LAP-IPAA patients (75 laparoscopic assisted, 25 hand assisted) were identified and case matched to 200 open IPAA control patients by age, operation, gender, date of operation, and body mass index. Operative and postoperative outcomes at 90 days were compared. Results:A total of 300 patients (180 female) with a median age of 32 years (range, 17–66 years), and a median body mass index of 23 kg/m2 (range, 16–34 kg/m2) underwent IPAA (100 LAP-IPAA, 200 open IPAA). Diagnosis (chronic ulcerative colitis 97%, familial adenomatous polyposis 3%) and previous operative history were equivalent between groups. One intraoperative complication occurred in each group. Overall, the laparoscopic conversion rate was 6%. Median operative time was longer for the LAP-IPAA group (333 minutes versus 230 minutes, P < 0.0001). LAP-IPAA patients had shorter median time to regular diet (3 versus 5 days), time to ileostomy output (2 versus 3 days), length of stay (4 versus 7 days), and decreased IV narcotic use (all P < 0.05.Postoperative morbidity was equivalent (LAP-IPAA = 33%, open IPAA = 37%), mortality was nil, and readmission rates were equal (LAP-IPAA = 21%, open IPAA = 22%). Reoperation was required in 3% of LAP-IPAA and 6.5% of open IPAA patients (P < 0.2) during the first 3 months. Conclusion:LAP-IPAA is equivalent to open IPAA in terms of safety and feasibility. In addition, LAP-IPAA provides significant improvements in short-term recovery outcomes.

Management of Crohn's disease of the ileoanal pouch with infliximab☆

OBJECTIVES:The occurrence of Crohns disease (CD) in a patient with an ileal-pouch anstomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients.METHODS:Medical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1–16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions.RESULTS:At a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3–44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab.CONCLUSIONS:Infliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients.

Effect of Age on the Enteric Nervous System of the Human Colon

Abstract  The effect of age on the anatomy and function of the human colon is incompletely understood. The prevalence of disorders in adults such as constipation increase with age but it is unclear if this is due to confounding factors or age‐related structural defects. The aim of this study was to determine number and subtypes of enteric neurons and neuronal volumes in the human colon of different ages. Normal colon (descending and sigmoid) from 16 patients (nine male) was studied; ages 33–99. Antibodies to HuC/D, choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and protein gene product 9.5 were used. Effect of age was determined by testing for linear trends using regression analysis. In the myenteric plexus, number of Hu‐positive neurons declined with age (slope = −1.3 neurons/mm/10 years, P = 0.03). The number of ChAT‐positive neurons also declined with age (slope = −1.1 neurons/mm/10 years of age, P = 0.02). The number of nNOS‐positive neurons did not decline with age. As a result, the ratio of nNOS to Hu increased (slope = 0.03 per 10 years of age, P = 0.01). In the submucosal plexus, the number of neurons did not decline with age (slope = −0.3 neurons/mm/10 years, P = 0.09). Volume of nerve fibres in the circular muscle and volume of neuronal structures in the myenteric plexus did not change with age. In conclusion, the number of neurons in the human colon declines with age with sparing of nNOS‐positive neurons. This change was not accompanied by changes in total volume of neuronal structures suggesting compensatory changes in the remaining neurons.

Laparoscopic-Assisted vs. Open Ileal Pouch-Anal Anastomosis: Functional Outcome in a Case-Matched Series

PURPOSEFunctional outcomes in laparoscopic-assisted ileal pouch-anal anastomosis have been incompletely studied. More than one-year follow-up has rarely been reported in these patients. This study was designed to assess operative, functional, and quality of life outcomes in patients with ulcerative colitis or familial adenomatous polyposis a minimum of one year after.METHODSThirty-three laparoscopic-assisted ileal pouch-anal anastomosis and 33 open ileal pouch-anal anastomosis patients, with a median of 13 months and minimum of 12 months follow-up, were identified from a prospective, laparoscopic database. Functional outcome was prospectively assessed by using a standardized survey. These cohorts were matched by individual patient for year of surgery, age, gender, body mass index, and indication.RESULTSMedian age was 27 years (open) and 28 years (laparoscopic). There were 27 females and 6 males in each group. All operations occurred between 1999 and 2001. Median body mass index was 22.3 (open) and 21.7 (laparoscopic) groups. There were no significant differences in diagnosis, use of diversion, and anastomotic technique. Postoperative morbidity occurred in 6 percent of the laparoscopic cases and 12 percent of the open cases. Functional outcome after a minimum of one year revealed equivalent median day and median nocturnal number of stools of six to seven and one to two respectively. Consistency of stool, medication usage, and continence were no different between groups. Daytime and nocturnal incontinence was similar. Quality of life in regard to social, home life, family, travel, sports, recreation, and sex life were equivalent.CONCLUSIONSThe function and quality of life outcomes for patients undergoing laparoscopic-assisted ileal pouch-anal anastomosis seem to be equivalent to our open experience. Laparoscopic-assisted ileal pouch-anal anastomosis offers selected patients a safe, feasible, and durable alternative.

COMBINED MODALITY THERAPY INCLUDING INTRAOPERATIVE ELECTRON IRRADIATION FOR LOCALLY RECURRENT COLORECTAL CANCER

PURPOSE To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). METHODS AND MATERIALS From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). RESULTS Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. CONCLUSIONS Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.

Sexual Function, Body Image, and Quality of Life after Laparoscopic and Open Ileal Pouch-Anal Anastomosis

PurposeThis study was designed to compare self-reported sexual function, body image, and quality of life outcomes among ulcerative colitis patients undergoing laparoscopic or open ileal pouch-anal anastomosis.MethodsBetween 1978 and 2004, 100 laparoscopic and 189 open operations were performed in patients who were identified from a previously published cohort. Patients were surveyed one year after operation to evaluate sexual function, body image, and quality of life.ResultsA total of 125 of 289 patients (43 percent) returned completed surveys. There were no significant differences in terms of demographics, complications, or long-term functional outcomes between those who completed the surveys and those who did not. There were no clinical differences in results between laparoscopic and open patients using the three survey instruments. Orgasmic function scores were lower in men who underwent laparoscopic ileal pouch-anal anastomosis (P < 0.05) compared with open ileal pouch-anal anastomosis. Overall, sexual function scores were equal to or better than normal values for men but were lower in women. Finally, overall body image and quality of life scores were above the means published for the United States.ConclusionsAfter ileal pouch-anal anastomosis, men and women reported excellent body image and high cosmetic and quality of life scores regardless of operative approach. Female sexual function was more adversely affected after ileal pouch-anal anastomosis than was male sexual function.

Surgical management of intestinal malrotation in adults: comparative results for open and laparoscopic Ladd procedures

BackgroundThis study aimed to characterize the clinical; features of intestinal malrotation in adults, and to compare the results for the open and laparoscopic Ladd procedures.MethodsBetween 1984 and 2003, 21 adult patients with a mean age of 36 years (range, 14–89 years) were surgically treated for intestinal malrotation. The clinical data collected included age, gender, presenting symptoms, diagnostic tests, type of operation, operative time, narcotic requirement, time to oral intake, length of hospital stay, and outcome. The groups (open vs laparoscopic) were comparatively analyzed using two-sample t-tests and Wilcoxon rank sum tests.ResultsThe two groups were similar in terms of age, clinical presentation, and diagnostic tests performed. The most common presenting symptoms were chronic abdominal pain, nausea, and repeated vomiting. Upper gastrointestinal barium studies (UGI/SBFT) were diagnostic for all patients with malrotation as compared with computed tomography (CT) scanning, which was falsely negative in 25% of patients. A total of 21 patients underwent the Ladd procedure, either open (n = 10) or laparoscopic (n = 11). Three laparoscopic procedures were converted to open. Overall, the laparoscopic group resumed oral intake earlier than the open group (1.8 vs 2.7 days; p = 0.092), had a shorter hospital stay (4.0 vs. 6.1 days; p = 0.050), and required less intravenous narcotics on postoperative day 1 (4.9 vs 48.5 mg; p = 0.002). The laparoscopic group underwent a longer operation (194 vs 143 min; p = 0.053). Sixteen of eighteen patients available for follow-up reported complete resolution of symptoms, 2 felt greatly improved. No patient required a second operation related to volvulus or recurrent symptoms.ConclusionsThe laparoscopic Ladd procedure is feasible, safe, and as effective as the standard open Ladd procedure for the treatment of adults who have intestinal malrotation without midgut volvulus. Patients also benefit from this minimally invasive approach, as manifested by an earlier oral intake, a decreased need for intravenous narcotics, and an earlier discharge from the hospital.