Biomedical subjects
J H Pemberton
Publications and source records attributed to J H Pemberton.
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.
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.
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.
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.
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.
Ileal pouch-anal anastomosis.
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Second look surgery--a shell game?
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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.
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.
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).
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.
Evaluation and surgical treatment of severe chronic constipation.
Patients with chronic constipation may have one of several physiologic disorders, not all of which are amenable to operative therapy. The aim of this study was to test colonic and pelvic floor function preoperatively, to identify patients suitable for surgery based on these studies, and to determine operative outcome over time. Between 1987 and January 1991, 277 patients referred for severe symptoms of chronic intractable constipation underwent colon transit studies, measurement of anal canal pressures and reflexes, and measurements of anorectal angle movements and efficiency of evacuation. Balloon expulsion studies, electromyography of the pelvic floor, and defecating proctograms also were done. Based on these studies, patients were categorized as having: slow transit constipation (STC), 29 patients; pelvic floor dysfunction (PFD), 37 patients; STC + PFD, combined slow transit and pelvic floor dysfunction, 14 patients; and irritable bowel syndrome (IBS), 197 patients. Slow transit constipation patients underwent abdominal colectomy and reanastomosis. Pelvic floor dysfunction patients underwent pelvic floor retraining only. Patients with STC + PFD underwent pelvic floor retraining followed by abdominal colectomy. Irritable bowel syndrome patients were treated symptomatically. Among the 38 patients operated on (STC and STC + PFD), there was no operative mortality. Prolonged ileus developed in 13%, and small bowel obstruction occurred in 11% of patients. On follow-up, a mean of 20 months after ileorectostomy, no patient was constipated, none required a laxative, and none was incontinent. The mean number of stools per day was four. The authors concluded that a prospective evaluation of colonic and pelvic floor function reliably delineated constipated patients with slow transit, suitable for operative management, from those with pure pelvic floor dysfunction or irritable bowel syndrome, who were not. Abdominal colectomy and ileorectostomy in the slow transit patients was safe and effective, resulting in prompt and prolonged relief of constipation.
Variations in muscle tone of the human rectum: recordings with an electromechanical barostat.
Rectal wall tone (the contractile state of the rectal tunica muscularis) should mediate accommodation and influence rectal emptying. Such changes in tone however can be only inferred from changes in baseline pressure recorded with conventional manometry. We used an isobaric volumetric device, the rectal electromechanical barostat, to quantify variations in tone of the rectal wall in response to feeding and to perturbations in response to the pharmacological agents neostigmine and glucagon. The barostat quantitates muscular wall tone indirectly by measuring its reciprocal, e.g., the volume of air within a flaccid intraluminal bag that is maintained at a constant and preselected pressure, by an electronic feedback mechanism. The barostat as well as a three-channel perfused manometric catheter were positioned in the rectum of 14 healthy volunteers. Three patterns of changes were observed: 1) respiratory fluctuations, 2) rapid volume waves, and 3) slow volume changes. Rectal tone varied little during fasting; rapid or slow changes in intrabag volume were infrequent. Ingestion of a standard meal was followed by a significant decrease in barostat bag volume (85 +/- 6 ml fasting vs. 50 +/- 8 ml fed, P less than 0.05). Pharmacological agents also induced predictable responses; neostigmine decreased bag volume and induced phasic pressure activity, whereas glucagon abolished phasic pressure activity and increased barostat bag volume. Perfused manometric catheters showed no concomitant changes in baseline pressure. We concluded that a rectal barostat measured variations in human rectal tone, which were not recorded by conventional manometric techniques. These changes in rectal tone might have important functional significance.
Quality of life after proctocolectomy. A comparison of Brooke ileostomy, Kock pouch, and ileal pouch-anal anastomosis.
Recent work has shown that patients undergoing proctocolectomy and ileal pouch-anal anastomosis experience a better quality of life than those undergoing proctocolectomy and Brooke ileostomy. To assess whether the improvement with the pouch is due to the absence of a stoma or the preservation of fecal continence, functional and performance activities were assessed in 406 patients with Brooke ileostomies (stoma present, incontinent), 313 with Kock pouches (stoma present, continent), and 298 with ileal pouch-anal anastomoses (stoma absent, continent). All patients underwent proctocolectomy for ulcerative colitis or familial adenomatous polyposis. After adjusting for age, sex, diagnosis, attitude towards the operation, dietary satisfaction, and ability to work, the likelihood of an impact on performance was estimated for the three types of operation using logistic regression analysis. Patients with ileal pouch-anal anastomoses had fewer restrictions in sports and sexual activities than those with Kock pouches (P less than 0.05), whereas those with Kock pouches in turn had fewer restrictions in these activities but more restrictions in travel than those with Brooke ileostomies (P less than 0.05). In contrast, performance in the categories of social life, recreation, work, and family was similar between groups. It is concluded that both the presence of a stoma and fecal incontinence impair the quality of life after proctocolectomy. Ileal pouch-anal anastomosis, which avoids both stoma and incontinence, offers the best quality of life between the three operations studied.
Transducer manometry and the effect of body position on anal canal pressures.
Anal canal manometry is performed conventionally with balloons, sleeves, perfused or nonperfused open-tipped catheters, or with multiport probes. The authors constructed a new manometer with four transducers embedded in a probe (15 mm outside diameter) and oriented radially, 90 degrees apart. The transducer probe was validated in 27 healthy volunteers by comparing its performance to that of a standard four-port perfused manometer and then used to measure anal canal and rectal pressures in body positions more physiologic (standing, sitting) than that usually employed (left lateral) for such measurements. Both devices measured similar anal canal resting pressure in the left lateral position (mid canal, 58 +/- 3 mm Hg perfused vs. 62 +/- 4 mm Hg transducer; P greater than 0.05). The transducer probe, however, recorded higher squeeze pressures (mid canal, 100 +/- 6 mm Hg perfused vs. 143 +/- 14 mm Hg transducer; P less than 0.05). The transducer probe detected higher intrarectal and resting anal canal pressures when subjects were standing or sitting, compared with the left lateral position (rectum, 3 +/- 1 mm Hg left lateral; 17 +/- 2 mm Hg standing; 20 +/- 1 mm Hg sitting; P less than 0.05; mid anal canal, 57 +/- 3 mm Hg left lateral; 86 +/- 4 mm Hg standing; 81 +/- 5 mm Hg sitting, P less than 0.05). The rise in resting anal canal pressure was uniform circumferentially. Neither anal canal length nor squeeze pressure changed with change in position. The authors concluded that 1) transducer manometry recorded similar resting but higher squeeze pressures compared with perfused manometry; 2) transducer manometry recorded the same radial variation in anal canal resting and squeeze pressures as that recorded by the perfused manometer; and 3) standing and sitting caused a four-fold rise in intrarectal pressure, which was associated with a concomitant rise in resting anal canal pressure.
Ileal pouch-anal anastomosis. Reoperation for pouch-related complications.
The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients.
Anorectal and pelvic floor disorders: putting physiology into practice.
The pathophysiology of the pelvic floor syndromes is complex and confusing. Childbirth is the only aetiological agent to have been clearly identified, but its role is not universal. Learned or psychogenic pelvic floor incoordination is likely to play a part. The conditions are so intertwined that an increasingly comprehensive battery of tests has become necessary to try to unravel the component disorders; anorectal physiology testing has therefore assumed an important position in the evaluation of these patients. It is only by careful application of physiological studies in clinical practice that further advances can be made. The investigations currently available can contribute significantly to determining the optimum management of these difficult patients. Surgical indications continue to be refined. The results of careful clinical and laboratory follow-up studies have led to changes in practice. The pelvic floor syndromes have only recently been defined; there is still much work to be done.