Immunohistochemical localization of insulin-degrading enzyme along the rat intestine, in the human colon adenocarcinoma cell line (Caco-2), and in human ileum.

Insulin-degrading enzyme (IDE) has been implicated in the intracellular degradation of insulin in insulin target cells. Knowledge of the existence of this enzyme in the intestine will be beneficial to the achievement of clinical oral efficacy of insulin. A comparative study was conducted with rat intestine, human colon adenocarcinoma (Caco-2) cells, and human ileum. Confocal microscopy analysis using the anti-IDE antibody showed that IDE was localized in the mucosal cells of rat and human intestines, as well as in Caco-2 cells. Immunostaining of this enzyme was homogeneous throughout the cell excluding nucleus, indicating a typical cytosolic distribution in rat and human enterocytes and in Caco-2 cells.

The presence of insulin-degrading enzyme in human ileal and colonic mucosal cells.

The aim of this research is to characterize the presence of insulin-degrading enzyme in human colon and ileal mucosal cells. Biochemical studies, including the activity-pH profiles, the effects of enzyme inhibitors, immunoprecipitation and western blots, were conducted. The majority of insulin-degrading activity in colon mucosal cells was localized in the cytosol. In both colon and ileum, cytosolic insulin-degrading activities had a pH optimum at pH 7.5, and were extensively inhibited by each of N-ethylmaleimide, p-chloromercuribenzoate, and 1,10-phenanthroline, but were very weakly affected by each of leupeptin, chymostatin, diisopropyl phosphofluoridate and soybean trypsin inhibitor. In the colon and ileum, more than 93% and 96%, respectively, of cytosolic insulin-degrading activities were removed by the mouse monoclonal antibody to human RBC insulin-degrading enzyme, as compared with less than 20% by the normal mouse IgG for both tissues. Further, a western blot analysis revealed that a cytosolic protein of 110 kD, in both human colon and ileum, reacted with the monoclonal antibody to insulin-degrading enzyme. It is concluded that insulin-degrading enzyme is present in the cytosol of human colon and ileal mucosal cells.

Symptomatic hemorrhoids: current incidence and complications of operative therapy.

Hemorrhoidal disease affects more than one million Americans per year. We reviewed the treatment pattern for patients who presented with symptomatic hemorrhoids to our large university-affiliated group practice over a 66-month period. Over 21,000 patients presented to the practice with bleeding, thrombosis, or prolapse. Only 9.3 percent of patients required operative therapy. Conservative therapy was given to 45.2 percent of patients, while rubber band ligation was performed on 44.8 percent of patients. We retrospectively reviewed the complications and length of stay for a subset of patients undergoing operative therapy during the 66-month study period. Postoperative urinary complications (retention or infection) were seen in 20.1 percent of patients. Delayed hemorrhage was seen in 2.4 percent of patients. In-hospital length of stay was 2.5 days, which is approximately two days less than the length of stay found in a similar review of our practice in 1978. We conclude that over 90 percent of symptomatic hemorrhoids can be treated conservatively or with rubber band ligation, and, as surgery is reserved for only the most severe cases, complication rates may not decrease. However, we expect that in-hospital length of stay will continue to decrease over the ensuing years.

Ileal pouch vaginal fistulas: incidence, etiology, and management.

Some of the initial problems associated with the ileoanal reservoir have been solved. In their place, other complications have been recognized. Among these, the ileal pouch vaginal fistula stands out as a recently recognized difficult management problem. This multicenter study was undertaken to gain insight into the causes for, and treatment of, pouch vaginal fistulas. Cases were gathered from 11 surgical practices throughout North America, in which the ileoanal reservoir procedure is frequently performed. Overall, 304 females had undergone ileoanal reservoir procedures by these surgical groups. Twenty-one patients developed 22 pouch vaginal fistulas for an overall incidence of 6.9 percent. Five additional patients with pouch vaginal fistulas, whose restorative proctocolectomies were done elsewhere, were referred to these surgeons for treatment. The courses of these 26 patients form the basis of this report. This study details the risk factors which predispose in the development of a pouch vaginal fistula, as well as the various treatment options available.

Intra-operative endoscopy. University of Minnesota experience.

This review of intraoperative endoscopies was undertaken to identify the accepted and the controversial indications, to report the results and complications, and to determine the impact the procedure had on the operation performed. This retrospective review identified 78 patients who had undergone 82 intraoperative endoscopic exams between 1981 and 1987. Sixty-nine patients underwent intraoperative colonoscopy (84%), six had upper enteroscopy (7%), and seven had total gut endoscopy (9%). Indications were as follows: the inability to fully colonoscope preoperatively (29%), Crohn's disease (19%), malignant polypectomy site (12%), gastrointestinal bleeding (12%), routine screening to rule out synchronous lesions (12%), non palpable colonic lesions (11%), and miscellaneous (4%). Intraoperative endoscopy was successful in 89 per cent of patients. The exams provided information that altered the planned operation in 27 per cent of cases. There were four complications that may have been related to the endoscopic exams. All resolved without the need for further surgery. It is concluded that intraoperative endoscopy can greatly influence the operation performed in a significant percentage of cases. The clear cut indications for its use at this time are location of malignant polypectomy sites, adhesions or tortuous colon that prevents complete preoperative colonoscopy, chronic gastrointestinal bleeding, and location of non palpable bowel lesions. Controversial indications that we feel will prove useful include Crohn's disease and acute gastrointestinal bleeding. Intraoperative endoscopy is best used as an adjunct to preoperative endoscopy and not as a substitute for it.

Tube decompression of the dilated colon.

With the technique described herein, decompression of a massively dilated colon is effectively accomplished, allowing resection to proceed safely. This method of decompression has allowed us to perform colonic resection in all patients with toxic megacolon seen in recent years. It is desirable to remove the infected and inflamed colon in such a circumstance. We have not resorted to blowhole colostomies in cases of toxic megacolon, as this leaves the colon, which is the septic source, within the abdominal cavity. This technique has also been used successfully to expedite subtotal colectomy and ileosigmoid anastomosis in patients with obstructing lesions of the left side. It allows colonic decompression and on-table bowel preparation by irrigation with antiseptics such as povidone-iodine (Betadine).

Palliation for rectal cancer. Resection? Anastomosis?

There is no agreement regarding the proper management of patients with advanced carcinoma of the rectum. We performed a study to clarify whether palliative resection with or without primary anastomosis is worthwhile and safe. Among 679 patients managed for cancer of the rectum, 125 were considered incurable and underwent palliative procedures. High and low anterior resections were performed in nine and 57 cases, respectively, abdominoperineal resection in 26, Hartmann's procedure in three, simple diverting colostomy in 17, and transanal excision in 13. The overall postoperative mortality rate was 0.8%. Postoperative morbidity was 18% in abdominal operations and none in local excisions. Among patients treated by abdominal resections, only one required subsequent reoperation for colonic obstruction secondary to local recurrence. The median survival was 6.4 months for patients treated by diverting colostomy, 14.8 months for abdominally resected cases, and 14.7 months for transanal excisions. We conclude that palliative resection, often with primary anastomosis or local transanal excision, can be done safely in patients with incurable rectal cancer. We believe this approach improves the quality of the remaining life for these patients.

A case of pancreatitis associated with gastrinoma.

A case is presented of a 56 year old man with a history of idiopathic pancreatitis and multiple admissions for Klebsiella sepsis from an intra-abdominal focus, who in February 1980, developed spontaneous jejunal perforations on two occasions due to multiple ulcers in the small intestine associated with multiple hepatic metastases from a gastrin-secreting islet-cell tumor (gastrinoma) of the pancreas. On searching the literature, no other record could be found of an association between pancreatitis and a gastrinoma, although in this patient the two disease processes appear to be inextricably related.

The ParkS S ileal pouch and anal anastomosis after colectomy and mucosal proctectomy.

Attention to detail is crucial to the success of the operation described. Surgeons contemplating performing it should first be experts in pelvic surgery and are advised to personally observe and participate in the procedure performed by surgeons currently experienced in this technique.

The management of procidentia. 30 years' experience.

This is a retrospective study evaluating 179 patients with complete rectal prolapse operated on at the University of Minnesota affiliated hospitals from 1953 to 1983 with no mortality. One hundred and two of 138 patients who underwent abdominal proctopexy and sigmoid resection were followed from six months to 30 years with a recurrence rate of 1.9 percent. Twenty-two of the 33 patients who underwent perineal rectosigmoidectomy were followed from six months to three years with no recurrence. Nine patients who underwent abdominal proctopexy and subtotal colectomy because of colonic inertia associated with procidentia were followed from one to six years with no recurrence. Patient interviews revealed that 72 to 80 percent considered their results as excellent or good. Incontinence or persistent constipation caused the remaining patients to consider their results fair or poor, despite anatomic correction of the prolapse. Abdominal proctopexy and sigmoid resection was more likely to result in improvement of continence than was perineal rectosigmoidectomy.

Surgical options in ulcerative colitis.

Five operative options are now available for treatment of ulcerative colitis: (1) proctocolectomy with ileostomy, (2) abdominal colectomy with ileostomy and retention of the rectum, (3) abdominal colectomy with ileorectal anastomosis, (4) proctocolectomy with creation of a continent stoma or conversion of a standard ileostomy after proctocolectomy to a continent stoma, and (5) restorative proctocolectomy. Each procedure has advantages and disadvantages. With careful assessment, the specific needs of each patient can best be met. In many cases a permanent stoma can be avoided. The newer procedures have not been used long enough for long-term effects to be known, and they must be offered with reservation and then only to well-informed, stable, and relatively fit and cooperative patients.

Modern management of hemorrhoids.

Hemorrhoids require therapy only when they cause symptoms. Early symptoms troubling the patient only occasionally are readily managed by dietary measures that increase the intake of fluids and fiber, such as bran, often supplemented by hydrophilic bulk-forming colloids, so that a bulky, soft stool is produced regularly. Rubber band ligation is the treatment of choice for small or moderate sized hemorrhoids with minimal prolapse, whether or not they bleed. Such bands should be applied to the mucosa at the anorectal junction and not directly to the hemorrhoidal tissue. Patients with large prolapsing or acutely thrombosed hemorrhoids are best managed by a closed type of hemorrhoidectomy. This technique is effective and safe and has great advantage with rapid healing and minimal postoperative care, which provides the patient with the maximum comfort. Complications are few and, in particular, anal stenosis or stricture is rare. Hemorrhoids occurring in association with other conditions require specific treatment only if they are responsible for symptoms in their own right, distinct from the associated condition. Other treatments discussed are effective but have particular disadvantages that make them unsuitable for routine use. Moreover, they offer no advances on the treatment regimens proposed.

Bilateral carcinoma of the breast.

A review of patients treated at the Peter MacCallum Clinic, Melbourne, between 1968 and 1973 inclusive, revealed 76 cases of primary carcinoma involving the opposite breast. Twenty-one of these occurred synchronously, when they were usually associated with elderly patients, a strong family history and an increased delay in presentation. The behaviour of these tumours was unremarkable, though the survival of the patients may have been less than those with single lesions, and in accord with the doubled risk of distant spread and local recurrence. Fifty-five patients with metachronous lesions did not present initally with features which would help to identify them as being prone to this double pathology. About 50% of the second carcinomas occurred within five years, but the remainder developed at intervals which were in several cases longer than 20 years. The patients did not present earlier on the second occasion, and several had advanced lesions. There was no evidence that the behaviour of the second carcinoma was influenced by immunological factors or patient susceptibility. Implications with regard to management are outlined, and the importance of long-term follow-up with regular examination is emphasized.

Women's attitudes to mastectomy for breast cancer.

One hundred patients who had been subjected to mastectomy for carcinoma were interviewed retrospectively to gauge their attitudes to any physical and/or emotional disabilities relating to their operation or disease. It was found that 40% of the patients had delayed for longer than a month after the onset of symptoms before seeking medical advice, but the reasons for this were not readily forthcoming. However, fear of mastectomy was not a common cause. Anxiety and embarassment due to an absent breast occurred in about one-third of patients, and did not diminish with time. Knowledge and the use of mammary prostheses was far from universal, and disturbingly only two-thirds were counselled in these matters by their medical advisers. Physical complications were common, particularly lymphoedema of the arm, and as expected this was closely related to the type and extent of treatment undertaken.

Major abdominal bleeding in chronic pancreatitis.

This case report concerns a patient with chronic pancreatitis which led to extensive retroperitoneal haemorrhage from a rupture of the abdominal aorta. The rarity of this complication is emphasized, but other reported instances of bleeding in association with chronic pancreatitis are commented upon.