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Biomedical subjects

J H Pemberton

Publications and source records attributed to J H Pemberton.

At least 91 records · Page 5Linked to original sources

Chronic pouchitis after ileal pouch-anal anastomosis: responses to butyrate and glutamine suppositories in a pilot study.

Nonspecific, idiopathic inflammation of ileal pouch mucosa ("pouchitis") after ileal pouch-anal anastomosis is a common complication of this surgical approach. The epithelium of the pouch is ileal, but variable degrees of colonic metaplasia are natural sequelae of construction of such a pouch. One hypothesis is that pouchitis is caused by a deficiency of epithelial nutrition. Thus, a lack of butyric acid (the principal metabolic fuel of colonocytes) or of glutamine (the main fuel of enterocytes) may develop. In this study, our aims were to determine the concentration of total short-chain fatty acids in random stool samples obtained from patients with an ileal pouch-anal anastomosis with and without pouchitis and to test the therapeutic effects of butyrate and glutamine suppositories on pouchitis. During the study, all conventional therapy for pouchitis was discontinued. For 21 days, 9 patients participated in a butyrate trial, and 10 patients were treated with glutamine. Total concentrations of fecal short-chain fatty acids were significantly less in patients with pouchitis than in those without pouchitis. During treatment, 6 of the 10 patients who received glutamine had no recurrence of symptoms, but only 3 of the 9 patients who received butyrate responded similarly. Hence, further studies of glutamine in the treatment of pouchitis seem warranted.

Adolescent↗

The ileal pouch operation for ulcerative colitis.

Ileal pouch-anal anastomosis cures chronic ulcerative colitis with an acceptable perioperative morbidity and mortality. The great majority of patients achieve satisfactory continence with an excellent quality of life. However, continence is not perfect, and fecal soilage is a troublesome problem for a small number of patients. Moreover, as many as one third of patients develop pouchitis, for which an effective means of long-term prevention or treatment has yet to be developed. Finally, controversial issues such as optimal pouch design or technique of anastomosis will be resolved only when long-term follow-up of randomized trials has been completed.

Colitis, Ulcerative↗

Pathophysiology of colonic motility disorders.

When no identifiable organic cause for colonic symptoms can be found, it is easy for the busy clinician to label the patient neurotic. It is evident that many of these "functional" disorders do reflect an underlying motility disorder, although our understanding is far from clear. However, currently, patients with severe constipation are evaluated in a much more rational manner and, as a consequence, are offered a reasonable therapeutic approach that can be predicted to have a good chance for success. We can hope that as our understanding of irritable bowel syndrome is strengthened, treatment will become more efficacious than the unproved and costly medications that are in use currently. Until dietary modification becomes commonplace, it is unlikely that the incidence of diverticular disease or its complications will change. Already, our understanding of ileus has allowed us to realize the benefits of laparoscopic surgery, and as our knowledge of the various gut hormones and the inhibitory role that some play in intestinal motility grows, ileus, and its resulting prolongation of hospital stay, may become less problematic.

Animals↗

Rectal wall contractility in healthy subjects and in patients with chronic severe constipation.

OBJECTIVE: The aim of this study was to identify differences in rectal wall contractility between healthy volunteers and patients with chronic severe constipation. SUMMARY BACKGROUND DATA: Whether motor function of the rectum contributes to slow-transit constipation is unknown. Measurements of rectal contractility have been performed traditionally with perfused catheters or microtransducers. The rectal barostat is a new technique that quantifies the volume of air within an infinitely compliant intrarectal bag maintained at constant pressure; decreases in bag volume therefore reflect increases in rectal muscular contractility (tone). Increases in volume reflect decreased contractility. METHODS: Fifteen healthy volunteers (ten women and five men; mean age, 36 years) and eight patients (seven women and one man; mean age, 44 years) were studied. Barostat recordings were made for 1 hour before and after a meal. Randomly, neostigmine (0.5 mg) or glucagon (1 unit) was then given intravenously. After 1 hour, the other medication was given. RESULTS: The fasting rectal volume was similar in the patient and control groups (113 +/- 7 mL vs. 103 +/- 4 mL, respectively; p > 0.05). Compared with controls, constipated patients had a significantly lower reduction in rectal volume after a meal (constipated, 35 +/- 8% vs. controls, 65 +/- 7%; p < 0.05) and after neostigmine administration (constipated, 39 +/- 6% vs. controls, 58 +/- 6%; p < 0.05). Moreover, constipated patients had a smaller increase in rectal volume after glucagon administration than did controls (28 +/- 6% vs. 64 +/- 18%, respectively; p < 0.05. CONCLUSIONS: Changes in rectal wall contractility in response to feeding, a cholinergic agonist, and a smooth muscle relaxant were decreased in constipated patients. These findings suggest that an abnormality of rectal muscular wall contractility is present in constipated patients.

Adult↗

Continence disorders.

Strategies to evaluate patients with continence disorders continue to evolve at a rapid pace. These novel methods quantify physiologic events that, in turn, facilitate increasingly accurate discrimination among the causes of incontinence and constipation. This review discusses recent advances in the causes, diagnostic approaches, and management options available for patients with continence disorders.

Anastomosis, Surgical↗

[Undetermined colitis].

Indeterminate colitis combines features of chronic ulcerative colitis and Crohn's colitis and contemplates a dilemma for the patient and surgeon contemplating ileal pouch anal anastomosis. Some series have reported a high incidence of failure of pouch procedures in patients with indeterminate colitis. A series reported by the authors in 1989 reported a failure rate on approximately 9% with indeterminate colitis. In updating this series with additional patients operated on since that time, the incidence in our series approaches 20%. We feel that an 80% success rate, however, justifies performing the ileal pouch anal procedure in carefully selected patients with indeterminate colitis, knowing that the failure rate may be somewhat higher than in patients with type ordainer chronic ulcerative colitis.

Colitis↗

Role of oxygen free radicals in the etiology of pouchitis.

Transient mucosal ischemia may cause oxygen-derived free radical production by xanthine oxidase, precipitating pouchitis after ileal pouch-anal anastomosis. Our aim, therefore, was to determine the effect of allopurinol, a xanthine oxidase inhibitor, in patients with acute and chronic pouchitis. Acute pouchitis was characterized clinically by sporadic episodes of increased frequency and decreased viscosity of stools, hematochezia, fever, malaise, and pelvic pain, which resolved promptly with treatment. Chronic pouchitis patients required continuous treatment to remain asymptomatic and invariably developed the signs and symptoms of pouchitis within one week following cessation of therapy. Eight patients with acute pouchitis were treated with allopurinol (300 mg p.o. b.i.d.) during the episode. Fourteen patients with chronic pouchitis had their standard antibiotic therapy discontinued while still asymptomatic; they were then given allopurinol (300 mg p.o. b.i.d.) for 28 days. Acute pouchitis resolved promptly in four of eight patients. Seven of the 14 patients with chronic pouchitis responded completely with no recurrence of symptoms during treatment. Allopurinol either terminated an episode of acute pouchitis or prevented pouchitis from recurring in 50 percent of patients. These data support a role for mucosal ischemia and oxygen free radical production in the etiology of pouchitis.

Acute Disease↗

Pouchogram: predictor of clinical outcome following ileal pouch-anal anastomosis.

UNLABELLED: Among 914 patients undergoing ileal pouch-anal anastomosis (IPAA) between January 1981 and June 1989, 463 (51 percent) had a pouchogram (meglumine diatrizoate [Gastrografin; E.R. Squibb & Sons, Inc., Princeton, NJ] enema) to assess anastomosis and ileal pouch integrity before closure of the ileostomy. The aim was to determine whether a pouchogram was useful in predicting clinical outcome. RESULTS: Abnormal findings were present in 74 patients (16 percent). These included anastomotic and pouch leaks and anstomotic strictures. Pouchograms were normal in the remaining 389 patients (84 percent). The incidence of significant anastomotic stricturing requiring dilatation under anesthesia was much higher in the abnormal than in the normal pouchogram group (33 percent vs. 4 percent, respectively; P less than 0.001). More significantly, an abnormal pouchogram was associated with an overall long-term failure rate of 23 percent, compared with 6 percent for a normal pouchogram (P less than 0.001). CONCLUSION: Abnormal findings in a pouchogram prior to ileostomy closure indicated those patients at high risk of long-term complications following IPAA.

Adolescent↗

Familial adenomatous polyposis: results following ileal pouch-anal anastomosis and ileorectostomy.

To compare the clinical and functional results of ileorectostomy (IR) and ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP), we reviewed the results of 94 IPAA patients and 21 IR patients who were operated upon between 1978 and 1988. The groups were similar with respect to age and sex. None of the patients died postoperatively. Postoperative complications occurred in 28 percent of the IPAA group and in 17 percent of the IR group (P greater than 0.1). Seven percent of IPAA patients described symptoms compatible with pouchitis. Sixty-one percent of IR patients required subsequent fulguration of rectal polyps at least once. IR patients had a mean (+/- SD) of 4 (+/- 2) stools per day, while IPAA patients had 5 (+/- 2) stools per day (P greater than 0.05). No significant difference in daytime soiling was present between IR (6 percent) and IPAA (4 percent). Nighttime spotting was also similar between the two groups. Nighttime soiling, however, was reported by 4 percent of IPAA patients but not by IR patients (P less than 0.05). One IPAA patient (1 percent) required pouch excision for a desmoid tumor, while two IR patients (11 percent) required proctectomy and ileostomy for recurrent dysplastic polyps (P less than 0.05). Adhesions and a shortened ileal mesentery prevented the construction of an ileoanal procedure in these latter patients. In conclusion, the postoperative complication rate and functional results are similar after IR and IPAA in patients with FAP; however, IR does not eradicate rectal polyps and may indeed preclude IPAA for those requiring subsequent proctectomy.

Adenomatous Polyposis Coli↗

Dysplasia in chronic ulcerative colitis: implications for colonoscopic surveillance.

Mucosal dysplasia has been used as a marker for patients with chronic ulcerative colitis considered to be most at risk of developing cancer, and its identification is the basis for colonoscopic surveillance programs. To evaluate the reliability of this premise, colectomy specimens from two groups of patients who had undergone surgery for chronic ulcerative colitis (50 with cancer and 50 without) were retrieved. The groups were matched by age, sex, duration of disease, disease extent, and symptoms at the time of surgery. Using a standard technique of multiple random biopsies, we utilized the standard colonoscopic biopsy forceps to obtain four biopsies from mucosa that was not macroscopically suspicious for dysplasia or cancer in eight defined regions in each of the 100 colon specimens. This technique mimicked exactly the methods used in our clinical surveillance program. All 3,200 biopsies were evaluated blindly by one pathologist for presence and grade of dysplasia. Twenty-six percent of colons with an established cancer harbored no dysplasia in any biopsy from any region in the colon. While an overall association between the presence of cancer and high-grade dysplasia was detected (relative risk = 9.00; 95 percent CI of 2.73-29.67), the sensitivity and specificity of random colonic biopsies to detect concomitant carcinoma were 0.74 and 0.74, respectively. These findings prompt concern that reliance on random biopsies, obtained during colonoscopic surveillance, may be misplaced.

Adult↗

Preservation of continence after ileoanal anastomosis by the coordination of ileal pouch and anal canal motor activity.

Nocturnal incontinence may occur after ileoanal anastomosis and may be related to loss of an effective anal canal pressure barrier during sleep; how pressure and contractions in the proximal bowel influence this barrier is unknown. Our aim was to evaluate the relationship between anal canal pressure and contractions and contractile activity of the pouch in continent subjects after ileal pouch-anal anastomosis (IPAA) and of the rectum in normal controls. A fully ambulatory system for 24-hour pressure recording was used. A flexible transducer catheter was introduced endoscopically so that sensors were at 2, 3, 8, 12, 16, and 24 cm from the anal orifice in 12 healthy controls (7 men, 5 women, mean age: 35 years) and 7 fully continent IPAA patients (4 men, 3 women, mean age: 34 years) more than 12 months postoperatively. Twenty-four hour spontaneous motor activity was stored in a 2.5 megabyte (MB) digital portable recorder. Mean anal canal pressure was calculated, and rectal motor complexes and ileal pouch large pressure waves were characterized. During sleep, resting anal canal pressures were similar in the two groups (72 +/- 12 mm Hg in controls versus 66 +/- 9 mm Hg in IPAA patients [mean +/- standard deviation (SD)], p = NS), but anal canal pressure showed cyclic relaxations (periodicity: 95 +/- 11 min in controls, 54 +/- 18 min in IPAA patients, p less than 0.05), during which the mean pressure trough was 15 +/- 4 mm Hg in controls and 14 +/- 5 mm Hg in IPAA patients (p = NS). In the control patients, during sleep, a mean of six rectal motor complexes were identified (range: 3 to 9). In patients with IPAA, during sleep, a mean of eight large pressure waves per hour were identified (range: 2 to 20). Importantly, in both controls and patients, rectal motor complexes or large pressure waves were always accompanied by rapid return of anal canal pressure from trough to basal values and increased contractile activity. We concluded that, in healthy patients and in continent patients after IPAA, motor activity of the rectum and of the ileal pouch was associated with changes in pressure and contractile activity of the anal canal so that rectal- and neorectal-anal canal pressure gradient, and, in turn, fecal continence were preserved.

Adult↗

Patterns of recurrence after curative resection of carcinoma of the colon and rectum.

Data on 818 patients who had undergone curative resection for Dukes' B2 or Dukes' C carcinoma of the colon and rectum were analyzed to determine the timing and patterns of recurrence based on such tumor characteristics as location, Dukes' stage, grade, ploidy and the presence of obstruction, perforation or adherence to adjacent organs or tissues. Three hundred and fifty-three patients (43 per cent) had recurrent disease. There was recurrence in 52 per cent of patients with carcinoma of the rectum and in 40 per cent of patients with carcinoma of the colon. The median time to recurrence for all patients was 16.7 months, with a range from 1 month to 7.5 years. Dukes' C lesions and the presence of adhesion or invasion, or both, or perforation were associated with significantly earlier recurrence. Among patients with recurrence, the most frequent sites were hepatic in 33 per cent, pulmonary in 22 per cent, local or regional, or both, in 21 per cent, intra-abdominal in 18 per cent, retroperitoneal in 10 per cent and peripheral lymph nodes in 4 per cent. Rectal primary sites, when compared with colonic, had proportionally more local or regional, or both, recurrences (p = 0.00003) and fewer involving retroperitoneal nodes (p = 0.022). Both primaries of the rectum and colon at stage C, when compared with stage B, had fewer local or regional recurrences, or both (p = 0.01), but a greater tendency to involve retroperitoneal or peripheral nodes. Primaries of the colon with adhesion to, or invasion of, adjacent organs had a lesser tendency to pulmonary metastasis (p = 0.036). Whereas the grade of anaplasia and ploidy had a strong influence on the rate of recurrence, they did not influence timing or patterns of recurrence. Patterns of recurrence based on the characteristics of the tumor may facilitate selection of the most appropriate adjuvant procedures, particularly those directed toward local or regional recurrence, or both, and also may guide efforts at early recognition of recurrence.

Adenocarcinoma↗

The effect of stool consistency on rectal and neorectal emptying.

Although stool consistency is considered to be an important component of anorectal continence, its effect on rectal emptying has never been quantitated. In 12 healthy volunteers and 12 patients after ileal pouch-anal anastomosis (IPAA) (46 +/- 5 months after the operation; mean +/- SEM), perfused anal manometry was performed; movements of the anorectal angle were quantitated scintigraphically; and rectal capacity and compliance were measured by air insufflation of an intrarectal balloon at three infusion rates. The efficiency of rectal evacuation of three consistencies (5 percent, liquid; 7.5 percent semisolid gel; 11.25 percent solid gel; w/w) of Tc99m labeled artificial stool (aluminum magnesium silicate gel) was quantitated by gamma camera imaging. No abnormalities of pelvic floor function were demonstrated in either controls or patients. The mean neorectal capacity and compliance of patients with IPAA did not differ from control, (capacity; IPAA: 215 +/- 22 ml vs. control; 245 +/- 29 ml; compliance; IPAA: 5.5 +/- 0.7 ml/cm H2O vs. control; 6.6 +/- 0.7 ml/cm H2O; P greater than 0.05). In controls, the percentage of the 7.5 percent consistency evacuated (81 +/- 5 percent, mean +/- SEM) was significantly more than the percentage evacuation of either the 5 percent consistency (67 +/- 7 percent) or the 11.25 percent consistency (77 +/- 2 percent) (P less than 0.05). After IPAA, the mean overall percent evacuation of the three stool consistencies was significantly less than control (52 +/- 6 percent after IPAA; 75 +/- 5 percent control, P less than 0.05). However, there was no significant difference in neorectal emptying between the liquid, the semisolid gel and the solid gel (56 +/- 6, 55 +/- 6, 51 +/- 9 percent, respectively, P greater than 0.1). We concluded that in healthy subjects but not in patients after IPAA, stool consistency affected the efficiency of evacuation of enteric content.

Adult↗

The risk of lymph node metastasis in colorectal polyps with invasive adenocarcinoma.

One hundred fifty-one patients with colorectal polyps containing invasive adenocarcinoma treated by resection were studied to determine the incidence of lymph node metastasis and whether lymph node metastasis was related to the depth of invasion. Other variables evaluated included size and configuration of the polyp, grade of adenocarcinoma, presence or absence of lymphovascular invasion, and degree of differentiation. In patients with sessile polyps, the incidence of lymph node metastasis was 10 percent. Eighty percent of these lesions had lymphovascular invasion. For pedunculated polyps, the overall incidence of lymph node metastasis was 6 percent. However, there was no incidence of lymph node metastasis when the depth of invasion was limited to the head, neck, and stalk of the polyp (Levels 1, 2, and 3). Only when the depth of invasion reached to the base of the stalk (Level 4) was the risk of lymph node metastasis high (27 percent). The other risk factors were not associated with lymph node metastasis. We concluded that the most significant risk factor for lymph node metastasis in patients with invasive carcinoma in a polyp was invasion into the submucosa of the bowel wall (Level 4).

Adenocarcinoma↗

Delayed ileal pouch-anal anastomosis. Complications and functional results.

In patients with chronic ulcerative colitis (CUC), ileal pouch-anal anastomosis (IPAA) can be performed either at the time of colectomy or as a delayed procedure after total abdominal colectomy and ileostomy. There has been debate as to whether delayed IPAA results in superior functional results, since patients are frequently steroid-free and have little evidence of active disease. To assess this, we analyzed 95 patients who had undergone total abdominal colectomy, either with ileostomy and Hartmann's procedure or with ileorectostomy, 2-183 months prior to IPAA. Postoperative complications and functional results were compared with those of 776 CUC patients who underwent IPAA at the time of abdominal colectomy. Indications for prior colectomy included toxic megacolon (40 percent), failed medical therapy (36 percent), other reasons (e.g., iatrogenic perforation, cancer) (6 percent), and reasons unclear (18 percent). Nineteen percent of delayed-IPAA patients were taking steroids at the time of pouch construction. Follow-ups were similar in the two groups. The incidence of septic and obstructive complications after delayed IPAA vs. IPAA at the time of colectomy were 10.5 percent vs. 5.4 percent and 6.5 percent vs. 14.5 percent, respectively. There were no significant differences in postoperative functional results between the two groups. Delayed IPAA confers no advantage over IPAA performed at the time of colectomy in terms of functional outcome. Delayed IPAA was associated with a significantly higher rate of septic complications but a lower incidence of postoperative obstruction.

Adolescent↗