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Biomedical subjects

R R Dozois

Publications and source records attributed to R R Dozois.

At least 73 records · Page 4Linked to original sources

Anti-tumor X anti-lymphocyte heteroconjugates augment colon tumor cell lysis in vitro and prevent tumor growth in vivo.

Cross-linking an anti-tumor antibody, specific for tumor cell surface antigens, and an anti-lymphocyte antibody, specific for the T lymphocyte receptor complex (TCR/CD3), produces a heteroconjugate that can direct T cells to lyse tumor cells. We tested the ability of anti-tumor X anti-lymphocyte (CD3) heteroconjugates to redirect human peripheral blood lymphocytes (PBLs) to lyse human colon cancer cells in cytotoxicity assays and in a murine colon tumor model. We demonstrated in vitro, that cultured human PBLs alone produced low levels of tumor lysis, but PBLs treated with anti-tumor X anti-CD3 heteroconjugates produced significantly greater tumor cell lysis (P less than 0.0025). Similarly, nude mice injected with LS174T human colon cancer cells and treated with cultured human PBLs and anti-tumor X anti-CD3 heteroconjugates survived significantly longer than saline control mice (P less than 0.01), or mice treated with PBLs alone (P less than 0.01), or heteroconjugates alone (P less than 0.05). F(ab')2 heteroconjugates were equally as effective in prolonging animal survival, but irrelevant heteroconjugates and monoclonal anti-tumor antibodies showed no therapeutic benefit. Anti-tumor X anti-CD3 heteroconjugates may represent an effective approach to tumor-specific cellular immunotherapy.

Animals↗

Bleeding from peristomal varices: perspectives on prevention and treatment.

Peristomal variceal bleeding is a serious complication in patients with chronic liver disease undergoing colon surgery with a stoma. Our aim was to examine the morbidity of bleeding for peristomal, perianastomotic, and esophageal varices in a group of patients with chronic liver disease who underwent colectomy at the Mayo Clinic between 1970 and 1988. Morbidity was evaluated in terms of the number of major bleeding episodes and the number of units of blood transfused. The treatment of bleeding was also evaluated. One hundred seventeen patients (74 males and 43 females) aged 11-78 years were studied. Sixty-two patients (53 percent) had a permanent stoma, while 55 patients (47 percent) had a colonic resection and anastomosis. Sixty-seven patients (62 percent) had chronic ulcerative colitis and primary sclerosing cholangitis. In the stoma group, bleeding appeared from stomal and/or esophageal varices in 19 patients (31 percent), while, in the non-stoma group, bleeding exclusively from the esophageal varices occurred in eight patients (15 percent). Perianastomotic variceal bleeding was never observed. The 5-year cumulative probabilities of one major bleed occurring from gastrointestinal varices appeared to be similar between the two groups. Patients who bled from peristomal varices with or without esophageal bleeding (n = 17) rebled more frequently (6.5 +/- 5.5 vs. 3 +/- 1.6; P less than 0.05) and were transfused more often (14.9 +/- 12.3 vs. 7.5 +/- 4.1; P less than 0.05) than patients who bled exclusively from esophageal varices (n = 10). No difference was found in the incidence of recurrent bleeding and the number of units of blood transfused between patients who bled exclusively from peristomal varices (n = 10) and those who bled from both peristomal and esophageal varices (n = 7). Medical and local measures were more effective in controlling esophageal bleeding than in controlling peristomal bleeding. Therefore, patients with chronic liver disease who must undergo colectomy should have a distal anastomosis rather than a terminal stoma.

Abdominal Muscles↗

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↗

Endorectal ultrasonographic staging of rectal carcinoma.

Endorectal ultrasonography is a valuable imaging method for examination of the rectum and perirectal tissues. We assessed 50 patients with known rectal carcinoma prospectively by using a 7.0-MHz endorectal transducer to determine the depth of invasion of the rectal wall by tumor and the presence of lymphadenopathy. Tumors were staged by using the Astler-Coller modification of the Dukes staging system, and the results were compared with histologic staging of the surgical specimen. Ultrasonography had an accuracy of 80%, a sensitivity of 92%, and a specificity of 76% for detection of invasion of the perirectal fat. Ultrasonography was sensitive in the detection of perirectal lymphadenopathy but was not specific in distinguishing benign from malignant nodes.

Adult↗

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.

Adenomatous Polyposis Coli↗

Pouchitis and extraintestinal manifestations of inflammatory bowel disease after ileal pouch-anal anastomosis.

Although the etiology of pouchitis after ileal pouch-anal anastomosis (IPAA) is unknown, its manifestations resemble those of nonspecific inflammatory bowel disease, including, anecdotally, the apparent ability to evoke extraintestinal manifestations (EIM) of inflammatory bowel disease (IBD). Our aim was to determine in what manner pouchitis and EIMs were associated. The computerized records of 819 consecutive patients who underwent IPAA between January 1981 and December 1988 were reviewed. Eighty-five patients were excluded (because of incomplete follow-up, death, or permanent ileostomy). Follow-up of the remaining 734 patients was complete (mean, 41 months). The mean age was 32 years and the ratio of men to women was 1:1. Ileal pouch-anal anastomosis was performed for chronic ulcerative colitis in 91% of patients and for familial adenomatous polyposis in 9%. Pouchitis occurred in 31% of chronic ulcerative colitis patients and 6% of familial adenomatous polyposis patients (p less than 0.01). The mean time to first occurrence was 17 months. Pouchitis recurred in 61% of patients at risk. Patients with preoperative and postoperative EIMs had significantly higher rates of pouchitis than did patients without EIMs (39% preoperative EIMs versus 26% with no EIMs, p less than 0.001; 53% postoperative EIMs versus 25% with no EIMs, p less than 0.001). Of patients with pouchitis in whom EIMs resolved after IPAA but then recurred (n = 12), EIMs recurred when pouchitis occurred and abated when pouchitis was treated in seven patients. We concluded that pouchitis occurred frequently after IPAA and that patients with EIMs were at higher risk of developing pouchitis than were patients who never had EIMs. Furthermore some patients experienced a temporal relationship between flares of EIMs and pouchitis. These results imply that pouchitis may be a novel manifestation of inflammatory bowel disease persisting after operation.

Adult↗

Leiomyosarcoma of the rectum and anus. A series of 22 cases.

Twenty-two patients with leiomyosarcoma of the rectum (n = 19) or the anus (n = 3) were treated surgically at the Mayo Clinic from 1950 through 1985. The majority of tumors occurred in men (1.4:1.0) during the sixth and seventh decades of life. Fifty-nine percent of the patients had symptoms including, most commonly, change in bowel habit, bleeding, and pain. Wide local excision was performed in 10 patients, whereas a more radical surgical procedure, including abdominoperineal resection (n = 8), pelvic exenteration (n = 2), and low anterior resection (n = 1), were performed in 11 patients. One tumor was unresectable. The overall survival until death from disease was 90% at 1 year, 74% at 5 years, and 51% at 10 years postoperatively. The percentage of patients free of disease at 1, 5, and 10 years postoperatively was 85, 62, and 40, respectively. Wide local resection was not superior to a more radical surgical approach in preventing tumor recurrence or improving survival. Lesions less than 2.5 cm and confined to the bowel wall can be treated by wide local excision, whereas larger or more extensive tumors should be treated by a more radical surgical approach.

Actuarial Analysis↗

Mesenteric fibromatosis complicating familial adenomatous polyposis: predisposing factors and results of treatment.

Between January 1975 and December 1983, 24 of 183 patients (13%) with familial adenomatous polyposis (FAP) seen at the Mayo Clinic had mesenteric fibromatosis (MF). MF was found most often in FAP patients with associated extra-colonic "Gardner" signs (19 patients) and those who had had previous abdominal surgery (20 patients). In 4 patients, MF appeared spontaneously. The male-to-female ratio was 0.4, with a median age of 31 years in women and 37 years in men. Ten of 24 patients (42%) had been asymptomatic prior to diagnosis at time of surgery for FAP. Complications of the disease included intestinal or urinary tract obstruction. Minimal surgical manipulation seemed to be associated with fewer postoperative complications and a lesser risk of regrowth of the tumor. Nonsurgical treatment, including tamoxifen and sulindac in combination, may be beneficial. Surgery should be reserved for relief of obstruction, and bypass is preferred to resection.

Adenomatous Polyposis Coli↗

Extended resection for locally advanced primary adenocarcinoma of the rectum.

To determine the perioperative mortality and morbidity and the longterm prognosis of patients undergoing extended pelvic resections for localized advanced primary adenocarcinoma of the rectum, the authors reviewed their experience with 65 patients operated on between 1956 and 1984. Local invasion without distant metastasis was present in all patients at operation and en bloc resection of all involved organs was performed with intent of cure. Average age at operation was 61 years; 15 (23 percent) were men and 50 (77 percent) were women. Operations included abdominoperineal resection in 37 patients (57 percent), low anterior resection in 20 patients (31 percent), and Hartmann procedure in 8 patients (12 percent). Additionally, 34 of 42 women (81 percent) with intact uteri underwent en bloc hysterectomy, 37 of 48 women (77 percent) with intact ovaries had oophorectomy, and 25 of 50 women (50 percent) had partial vaginal resection. Seventeen of the 65 patients (26 percent) had a cystectomy, and 2 patients had a portion of small intestine resected in continuity with their tumor. Pathologic examination revealed lymph node involvement in 29 patients (45 percent) and histologic confirmation of adjacent organ extension in 37 patients (57 percent). There were no perioperative deaths, the average survival was 5.7 years, and 25 patients (38 percent) were alive after a mean follow-up period of 9.3 years. Overall five-year survival was 52 percent. Forty patients died during the follow-up period, with 26 (65 percent) of the deaths attributable to either recurrent carcinoma (25 patients) or a new primary lesion (1 patient). The cumulative probability of tumor recurrence at five years was 39 percent.

Adenocarcinoma↗

Clean sweep of the colon. The use of intraoperative colonoscopy.

Since 1982, intraoperative colonoscopy has been performed on 66 patients. Preoperative intent was to perform a colonoscopic polypectomy during an intra-abdominal procedure in 44 patients, localize lesions that might subsequently lead to either colon resection or colotomy and polyp excision in 13, localize bleeding sites in 4, determine the extent of inflammatory bowel disease in 2, survey the colon in 2 who did not have preoperative colon radiography, and assess bowel viability in 1. Surgery proceeded as planned in 54 patients; however, colonoscopic findings extended the resection to include additional segments of bowel in 4. In four patients, polypectomy or bowel resection was avoided as a result of the colonoscopic findings. Intraoperative colonoscopy was not possible in four patients. No complications were related directly to this procedure. Intraoperative colonoscopy is a useful adjunct for localizing lesions or "clearing" the colon. In some patients, colonoscopic findings may change the extent of resection performed.

Aged↗

Outcome of "indeterminant" colitis following ileal pouch-anal anastomosis.

To establish whether patients with indeterminant colitis (patients with ulcerative colitis whose surgical specimens also show features of Crohn's colitis) have an adverse outcome after ileal pouch-anal anastomosis (IPAA), the authors reviewed the pathologic reports and postoperative status of 514 consecutive patients who underwent IPAA for chronic ulcerative colitis (CUC). Twenty-five patients (5 percent) had features of indeterminant colitis (IC), including unusual distribution of inflammation, deep linear ulcers, neural proliferation, transmural inflammation, fissures, creeping fat, and retention of goblet-cell population. The clinical and functional outcome of these 25 IC patients was compared with that of the remaining 489 CUC patients. The mean follow-up was 38 +/- 18 months. No significant differences in complication rates, pouch function, incidence of "pouchitis," or requirement for pouch excision were detected in the two groups at follow-up. Although the authors are continuing to perform IPAA on patients with IC, a better definition of the IC patient and a more objective, prospective analysis of outcome of IC following IPAA is required before confident and specific treatment policies can be recommended.

Adult↗

The effect of pregnancy and delivery on the ileal pouch-anal anastomosis functions.

Since 1981, a total of 729 ileal pouch-anal anastomoses have been performed at the Mayo Clinic-affiliated hospitals. Three hundred fifty-four were in women. Twenty of these patients subsequently had at least one successful pregnancy and delivery. Eleven deliveries were vaginal with episiotomy, and nine were cesarean sections. No maternal deaths occurred. One child died of hyaline membrane disease. The frequency of nocturnal stooling increased in the ileal pouch-anal anastomosis patients during pregnancy (P less than .01), and the increase persisted for three months after delivery (P less than .05). In contrast, the frequency of daytime stools, the incidence of incontinence, the consistency of the stool, and the development of perineal seepage or skin irritation were not greatly altered by pregnancy or delivery. Moreover, postpartum pouch function was not influenced by the type of delivery (vaginal vs. cesarean section). In conclusion, pregnancy and delivery are safe in patients with the ileal pouch-anal anastomosis, but they lead to more frequent nocturnal stools. The type of delivery (vaginal vs. cesarean section) does not influence pouch functional outcome.

Anal Canal↗

Long-term survival and patterns of failure after postoperative radiation therapy for subtotally resected rectal adenocarcinoma.

Between 1977 and 1984, 17 patients received external beam irradiation after subtotal resection of rectal carcinoma. Ten patients had microscopic residual disease and 7 had gross residual disease. In the group with microscopic residual disease, 4 had tumor cut through with pathologically involved margins, 5 had adjacent unresected structures that were biopsy positive, and 1 had tumor spillage into the pelvis. The patients with gross residual disease were noted by the surgeon to have visible tumor after maximal debulking. Nine of 17 cases had involved pelvic lymph nodes. Radiation was administered to the pelvis with 4, 6, or 10 MV photons. Doses ranged from 40 to 60 Gy, with a median dose of 50 Gy given at 1.8 to 2.0 Gy per fraction, 5 days per week. Three patients received bacillus Calmette-Guérin (BCG), 2 received 5-fluorouracil (5-FU), and 1 received hycanthone. Thirteen of the 17 patients (76%) experienced local failure and, of these, 10 also developed distant disease. No patients developed distant metastasis in the absence of local failure. Local control was achieved in 3 of 10 patients (30%) with microscopic residual and 1 of 7 (14%) with gross residual. Four of the 17 patients (24%) have remained free of disease for greater than 5 years. External beam irradiation is capable of producing long-term survival and local control in a minority of patients with rectal cancer after subtotal resection. Investigation of more aggressive forms of therapy such as the addition of intraoperative irradiation, brachytherapy, radiation dose modifiers, and chemotherapy is warranted.

Adenocarcinoma↗

Small intestinal obstruction complicating ileal pouch-anal anastomosis.

Small bowel obstruction remains the most common complication after proctocolectomy with ileal pouch-anal anastomosis. Of 626 patients who underwent this operation between January 1981 and October 1986 for ulcerative colitis (544 patients), familial adenomatous polyposis (72 patients), or indeterminate colitis (ten patients), 17% developed small bowel obstruction, 7.5% of whom required surgical intervention. The obstruction occurred either before or after closure of the temporary ileostomy. Patients who had a temporary Brooke ileostomy were more likely to develop obstruction (four of 32 patients, 12.5%) than those who had a loop ileostomy (25 of 564 patients, 4.6%) (p = 0.07). Also, patients who had had previous operations were at greater risk of obstruction (8.5%) than those who had not (2.2%) (p less than 0.04).

Adenomatous Polyposis Coli↗

Elective colon and rectal surgery without nasogastric decompression. A prospective, randomized trial.

Nasogastric (NG) decompression after colorectal surgery is practiced commonly. Our aim was to determine whether routine NG decompression benefitted patients undergoing this type of surgery. Five hundred thirty-five patients were randomized prospectively to either NG decompression or no decompression. Stratification was by type of operation and patient age. Excluded were patients who had emergency surgery with peritonitis, extensive fibrous adhesions, enterotomies, previous pelvic irradiation, intra-abdominal infection, pancreatitis, chronic obstruction. prolonged operating times, or difficult endotracheal intubation. Two hundred seventy-four patients received NG decompression (Salem sump, Argyle Co., Division of Sherwood Medical, St. Louis, MO) and two hundred sixty-one did not. There were 33 protocol violations included in the 535 patients. Patients who were not decompressed experienced significantly more abdominal distention, nausea, and vomiting than did those patients who were. Moreover, 13% required subsequent NG decompression as opposed to a reinsertion rate of 5% for patients routinely decompressed. The mean length of hospitalization for both groups was 11 days. There were no significant differences in nasopharyngeal or gastric bleeding, inability to cough effectively, respiratory infections, wound disruptions, reoperation, and wound infection rates (5%) between the two groups. We conclude that even though there is an increase in the rate of minor symptoms of nausea, vomiting, and abdominal distention, routine nasgastric decompression is not warranted after elective colon and rectal surgery.

Adolescent↗

Ileal pouch-anal anastomosis: comparison of results in familial adenomatous polyposis and chronic ulcerative colitis.

The aim of this study was to compare the immediate postoperative results and the long-term outcome of ileal pouch-anal anastomosis in 94 patients with familial adenomatous polyposis to those in 758 patients with ulcerative colitis. Two colitis patients died after operation (0.3%), but no polyposis patients died. Overall operative complications appeared in 26% and 29% of polyposis and colitis patients, respectively (NS). Reoperation for intestinal obstruction did not differ between the two groups, but sepsis requiring reoperation was more common in colitis patients (6%) than in polyposis patients (0%, p less than 0.04). At follow-up (mean, 3 years), polyposis patients had fewer daytime stools (4.5 stools per day), less nighttime fecal spotting (26%), and less pouchitis (7%) than colitis patients (5.8 stools per day; spotting, 40%; pouchitis, 22%; p less than 0.002). The conclusion was that polyposis patients tolerated the operation better and had less long-term disability than did colitis patients. The data suggest that postoperative sepsis, daytime stooling frequency, nocturnal incontinence, and pouchitis may be, at least in part, disease related and not surgeon or operation related.

Adenomatous Polyposis Coli↗