Lars Liljeqvist

Pouchitis following pelvic pouch operation for ulcerative colitis

AIM: This study was undertaken to assess the risk for pouchitis in patients with ulcerative colitis who underwent surgery with colectomy, restorative pelvic pouch, and ileoanal anastomosis and to evaluate possible factors predictive for pouchitis development. PATIENTS AND METHODS: All patients receiving a pelvic pouch because of ulcerative colitis at Huddinge University Hospital between 1980 and 1993 (n=149; 89 men) were prospectively evaluated for symptoms suggestive of pouchitis. Diagnosis of pouchitis was based on occurrence of certain symptoms in combination with endoscopic findings. Pouchitis was divided into mild and severe, and the time span until the first attack of mild or severe pouchitis was calculated for each patient. RESULTS: Median follow-up time was 54 (5–152) months. The absolute cumulative risk of developing mild pouchitis was 21, 26, and 39 percent at 6, 12, and 48 months, respectively. The corresponding cumulative risk of developing severe pouchitis was 9, 11, and 14 percent, respectively. Risk for both groups together was 51 percent at 48 months. The occurrence of pouchitis, calculated at six-month intervals after closure of the loop ileostomy, was highest (23.1 percent) during the first six months. Incidence during the next six-month period was 11.4 percent and then only 3.1 percent thereafter. Thirty-two patients (21.5 percent) had chronic continuous symptoms requiring long-term metronidazole treatment, and 14 (9.4 percent) of those had chronic severe pouchitis. In two patients, removal of the pouch and permanent ileostomy became necessary. Extracolonic manifestations and early onset of ulcerative colitis were predictive factors for developing pouchitis. Former smoking seemed to be a protective factor. CONCLUSION: The risk for pouchitis was highest during the initial six-month period. Cumulative risk leveled off after two years but was substantial (51 percent) at four years. Less than 10 percent of patients had severe, chronic pouchitis, and only two patients (1.3 percent) had their pouches removed.

Long-term histomorphological surveillance of the pelvic ileal pouch: Dysplasia develops in a subgroup of patients

BACKGROUND & AIMS Little is known about the long-term morphology of the pelvic ileal pouch after restorative proctocolectomy in patients with ulcerative colitis. This study analyzed the mucosal adaptation in the pouch during a long-term follow-up. METHODS Mucosal biopsy specimens were obtained from 87 patients during a follow-up of 6.3 years (SD, 2.7; range, 3-14 years). The villous surface density, degree of inflammation, and type of mucin were determined from glycolmethacrylate-embedded sections. RESULTS Three basic patterns of mucosal adaptation were observed: regular response with normal mucosa or mild villous atrophy and no or mild inflammation (type A, 51%), transient atrophy response with temporary moderate or severe villous atrophy followed by normalization of architecture (type B, 40%), and constant atrophy response with permanent subtotal or total villous atrophy developing from the early functioning period accompanied by severe pouchitis (type C, 9%). Low-grade dysplasia occurred in 3 patients with type C response. CONCLUSIONS In a small group of patients with ulcerative colitis, the mucosa of the pelvic pouch adapts with constant severe villous atrophy accompanied by long-standing pouchitis. This group of patients should be identified and undergo regular endoscopic and histomorphological surveillance because of risk of developing neoplasia in the pouch mucosa.

Neoplastic Transformation of the Pelvic Pouch Mucosa in Patients With Ulcerative Colitis

BACKGROUND & AIMS Some patients with ulcerative colitis (UC) receiving an ileal pelvic pouch with ileoanal anastomosis (IPAA) develop persistent severe villous atrophy in the pouch mucosa. To investigate if mucosal atrophy indicates a risk for subsequent neoplastic transformation of the ileal pouch mucosa, a follow-up study was undertaken. METHODS Seven patients with UC and an IPAA in whom persistent severe atrophy (type C) developed and 14 control patients with no or only slight atrophy (type A) were prospectively surveyed by flexible videoendoscopy with multiple biopsies for assessment of possible neoplastic changes. RESULTS The median time of the pouch in function was 9 years for both groups. Dysplasia was found in 5 of 7 patients in the type C group (71%) compared with none in the type A group (P < 0.001). Four patients had low-grade dysplasia, and 1 patient had sequential multifocal development into high-grade dysplasia. Multifocal DNA aneuploidy was found in 2 patients, 1 with low-grade and 1 with high-grade dysplasia. CONCLUSIONS Patients with UC and a long-standing IPAA who develop persistent severe mucosal atrophy are at risk also of neoplastic transformation of the pouch mucosa.

Biliary lipid output and bile acid kinetics in cholesterol gallstone disease: Evidence for an increased hepatic secretion of cholesterol in Swedish patients

Sweden has one of the highest incidences of gallstone disease in the Western world. It is therefore important to characterize the mechanisms responsible for the formation of cholesterol gallstones in this population. In the present study, we have determined the kinetics of the two primary bile acids, cholic acid and chenodeoxycholic acid, and the hepatic secretion rates of the biliary lipids in 21 normolipidemic, nonobese gallstone patients (13 with functioning and 8 with nonfunctioning gallbladder) and in 23 healthy controls. The cholesterol saturation of fasting gallbladder bile averaged 110% in the gallstone patients with functioning gallbladder and 82% in the controls. The pool sizes of cholic acid and chenodeoxycholic acid were reduced by about 40% in the two groups of gallstone patients, whereas the rates of synthesis were close to normal. The fractional catabolic rate of both bile acids was increased in both groups of gallstone patients. The gallstone patients with functioning gallbladder had an increased (about 50%) cholesterol secretion but normal bile acid and phospholipid secretion rates. In the gallstone patients with nonfunctioning gallbladder the secretion rates of biliary lipids were not significantly different from those of the controls. The ratio between cholesterol and bile acids was about 50% higher in the gallstone patients with functioning gallbladder than in the controls or in those with nonfunctioning gallbladder. The results indicate that the hepatic secretion of cholesterol is an important determinant for the development of saturated gallbladder bile in Swedish gallstone patients.

Dysplasia and DNA aneuploidy in a pelvic pouch

A patient with an 18-year history of ulcerative colitis was operated on with colectomy, mucosal proctectomy, ileoanal anastomosis, and an S-type pelvic pouch due to intractable chronic continuous disease. The patient was followed by endoscopic controls and biopsy sampling from the pouch at regular intervals. A gradual development of severe atrophy in the ileal mucosa was followed by the development of low grade dysplasia. At the most recent endoscopic control, 4 years after the construction of the pouch, biopsies were sampled also for flow cytometric DNA analyses. DNA aneuploidy was detected in a biopsy from the center of the pouch, and a biopsy taken immediately adjacent showed low grade dysplasia. These findings underline the importance of endoscopic follow-up after construction of a pelvic pouch and focus attention to the potential of malignant transformation of the mucosa.

Different types of mucosal adaptation in the ileal reservoir after restorative proctocolectomy

A histomorphologic study of the pelvic pouch mucosa during the first two years of function was performed in 11 consecutive patients treated for ulcerative colitis. Two types of mucosal adaptation were delineated. Type A response (5 patients) showed stable slight atrophy, normal numbers of goblet cells, and numerous sulphated mucin positive cells. The frequency of mitoses was higher than in the normal ileum. The degree of acute and chronic inflammation was low and decreasing or stable. Dysplasia was never seen. Type B response (5 patients) comprised progressive, finally severe atrophy accompanied by increasing degree of acute inflammation. The number of mitoses was higher than in type A response. In two patients the number of goblet cells was moderately/severely decreased and epithelial atypia or low grade dysplasia occurred repeatedly. The response was regarded as indeterminate in one patient. The determination of the types of mucosal adaptation may help in the planning of the follow‐up of these patients.

A reconstructive operation on malfunctioning S-shaped pelvic reservoirs

Patients with triple-loop pelvic reservoirs have often suffered from evacuation problems, clinically shown as the need for intubation, frequent stooling, leakage or ileoanal disruptions. In a recent study, the authors have shown that malposition of the reservoir and presence of a long, kinked, efferent limb constitute the main causes of these problems. A corrective operation consequently was designed in order to improve pouch topography. The pouch and its efferent conduit were completely mobilized and the efferent limb was shortened considerably. The reservoir then was placed in close proximity to the anus and the ileoanal anastomosis was reestablished. This operation now has been performed in seven patients who were considered “failures” and the results are gratifying. Six of these patients now have efficient evacuation and four are completely without leakage. Comparison of pre- and postoperative clinical and radiologic variables confirm the strong correlation between reservoir topography and clinical outcome.

Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides.

The mucosal blood flow in pelvic pouches in man

Fluorescein flowmetry implies the measurement of capillary blood flow, expressed as an index between the maximum fluorescence after the first circulatory passage of sodium fluorescein (NaF) and the rise time, defined as the time interval between ten and 90 percent of the maximum fluorescence. A mathematic model based on fluorescein flowmetry was deduced to distinguish a mucosal and muscular blood flow in an intact (unopened) intestine during surgery in man. The hypothesis was that if, at a certain point in time, there is a fixed relationship between the seromuscular fluorescence and the mucosal maximum fluorescence, obtained during the first circulatory passage of NaF, and if the rise times were equal, then a mucosal blood flow could be calculated based on the seromuscular fluorescence. The model was tested in intestinal anastomoses on 16 patients. A fixed relationship between the numeric value of the mucosal maximum fluorescence and the seromuscular fluorescence was found. After five minutes, the ratio was 1:1 and the correlation coefficient at its highest (0.97). It was also found that the rise times were practically identical (r=0.92). The validity of the model was then tested by comparing it with fluorescein flowmetry, and the correlation coefficient was 0.85. The model was therefore accepted and named indirect mucosal fluorescein flowmetry. Indirect mucosal fluorescein flowmetry was applied to measure blood flow in pelvic pouches in 14 patients, and fluorescein flowmetry in the ileoanal anastomoses in eight patients. The mucosal blood flow in the reservoir, compared with the normal intestine, was reduced to 58 percent if the ileocolic artery or distal branches of the mesenteric artery were ligated, and to 88 percent if the vessels were left intact (P<0.05). In the ileoanal anastomosis the mucosal blood flow was reduced to 23 percent compared with the normal intestine (P<0.01). The results suggest that stretching and compressing the mesentery might be critical for circulation in the ileoanal anastomoses.

Gains and losses with stapling and omission of loop ileostomy in pelvic pouch surgery: a matched control study

Abstract After 10 years experience of pelvic pouch surgery with handsewn pouch and ileoanal anastomosis, mucosectomy, and covering loop ileostomy, the surgical technique was altered. Twenty patients were operated on with staple technique in pouch and ileoanal anastomosis but without mucosal proctectomy and loop ileostomy. This study group was compared with a matched control group of patients from our previous series with respect to duration of surgery, blood loss, hospital stay, complications, and functional outcome after 2 months, 12 months, and 60 months. It was found that staple technique significantly reduced the duration of surgery and the need of blood transfusions. Length of hospital stay after pouch surgery did not differ between the two groups, but omitting loop ileostomy reduced total hospital stay by about 2 weeks. Ileoanal anastomotic insufficiency occurred in two patients in the study group. Treatment by establishment of a defunctioning loop ileostomy, local saline perfusion, and administration of antibiotics was successful; the anastomosis healed within 2 weeks, and the long-term functional outcome did not differ from the average. Increased temperature persisted postoperatively in seven patients in the study group. Transient peroneal paresis occurred in three patients in the control group. Only in the control group was there stenosis in the ileoanal anastomosis requiring dilatation and fibrosis at the levator plane demanding emptying by a catheter. Concerning functional outcome, nighttime continence was significantly better in the study group than in the control group. The evacuation rate per 24 h was significantly higher in the study group after 2 and 12 months but not after 60 months. The outcome concerning other functional parameters such as urgency to evacuate, capacity to discriminate between gas and stool, deferral time, and perianal symptoms, did not differ significantly. Staple technique without mucosal proctectomy and loop ileostomy thus results in shorter duration of surgery and shorter hospital stay. In patients with increased risk of insufficiency of the anastomosis, however, covering loop ileostomy may be justified because of the risk for more serious consequences if anastomotic leakage occurs.