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Biomedical subjects

G E Block

Publications and source records attributed to G E Block.

At least 37 records · Page 2Linked to original sources

Ras oncogene and the acquisition of metastasizing properties by rectal adenocarcinoma.

To gain a better understanding of the biologic development of rectal adenocarcinomas, the authors evaluated the level of ras gene protein product (p21) in the available material of 74 Dukes' B adenocarcinomas, 64 Dukes' C adenocarcinomas, and 60 lymph-node metastases resected at the University of Chicago Medical Center between 1965 and 1981. Pathologic slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution giving definitive staining using the avidin-biotin peroxidase method. The analysis indicated that a higher percentage of Dukes' stage C rectal adenocarcinomas had high (greater than or equal to 1:40,000) p21 titers than Dukes' B adenocarcinomas (68.8 vs. 51.4 percent, respectively, P less than 0.05). In view of recent data suggesting that ras oncogene expression confers invasive and metastatic capabilities to NIH 3T3 cells, the authors believe this study offers evidence that overexpression of ras oncogene with overproduction of p21 protein product may be an important prerequisite for the acquisition of metastatic capabilities in the early stages of colon cancer.

Adenocarcinoma↗

Experience with 647 consecutive tumors of the duodenum, ampulla, head of the pancreas, and distal common bile duct.

Between 1946 and 1987, 647 patients with periampullary tumors were diagnosed at the University of Chicago Medical Center. These included 549 tumors located in the head of the pancreas, 40 in the distal common bile duct, 29 in the duodenum, and 29 at the ampulla of Vater. Ninety-eight per cent of all tumors were adenocarcinoma, with 93% of the remaining being duodenal carcinoid or sarcoma. Operability rate ranged from 81% to 97%, according to the tumor location and histologic type. A combination of laparotomy, biopsy, and bypass was performed in 433 patients and only one survived 5 years (0.2%). Resectability rate ranged from 16.5% for pancreatic adenocarcinoma to 89.3% for ampullary tumors. Of the 133 resections, 80 were pancreatoduodenectomies, 29 total pancreatectomies, 7 duodenectomies, 2 gastrectomies, 8 common bile duct resections, and 7 local excisions. Overall 19% of patients who underwent radical resection died in the immediate postoperative period, although mortality has decreased to 5% since 1981. Mortality was 20% after a standard pancreatoduodenectomy and 24.1% after a total pancreatectomy. Five-year actuarial survival rates, including perioperative deaths, were 8.8%, 20%, and 32% for pancreatic, duodenal, and ampullary adenocarcinoma, respectively. One half of patients with sarcoma and two-thirds with carcinoid of the duodenum survived 5 years. No patient with distal common bile duct adenocarcinoma achieved a 5-year survival rate. Multivariate analysis on all patients operated on (n = 566) revealed that the 5-year survival rate was significantly related to intent of operation (palliative 0.2%, curative 12%; p less than 0.001), histologic type (adenocarcinoma 2%, carcinoid and sarcoma 31%; p less than 0.0001), and site (ampullary and duodenal 21%, biliary and pancreatic 0.9%; p less than 0.001). A second multivariate analysis, evaluating only those patients with adenocarcinoma who survived the perioperative period of the radical resection (n = 97) analyzed the influence of tumor size and differentiation, lymphatic, capillary, and perineural microinvasion, lymph node status, and type of procedure (pancreatoduodenectomy vs. total pancreatectomy) on 5-year survival. None of these additional variables was significantly associated with long-term survival rates. In addition we evaluated the presence of local or distant recurrence after resection by analyzing the findings from all autopsies performed on these patients (n = 49): 29.4% of patients died with local recurrence alone, 23.5% with distant recurrence alone, and 47.1% had both local and distant recurrences.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Biliary stone disease in adults with cystic fibrosis.

A 27-year-old woman with cystic fibrosis had a 6-month history of fatty food intolerance and biliary colic. Ultrasonographic studies confirmed the presence of gallstones. A cholecystectomy and appendectomy were performed. An intraoperative cholangiogram showed anomalous drainage of the cystic duct into an accessory right hepatic duct. Patients with cystic fibrosis now commonly survive into adulthood and are at high risk for the development of cholelithiasis. The diagnosis may be obscured by other common gastrointestinal complications of cystic fibrosis. Optimal surgical management includes meticulous preoperative and postoperative pulmonary care. The surgeon must also have a thorough knowledge of the biliary tract anomalies that have been described in patients with cystic fibrosis.

Adult↗

Colon cancer: diagnosis and prognosis in the elderly.

Cancer of the colon and rectum appear to be epidemic in the US, with 150,000 cases expected during 1988. Two thirds of these patients are over age 60, and two thirds also have either full penetration of the bowel wall or metastases to regional lymph nodes. Mass screening via tests for occult blood in the stool is invaluable for detecting early carcinomas of the colon and rectum. Digital examination, endoscopy, and barium contrast radiographs help to confirm the diagnosis. Tumors of the colon and rectum are best treated operatively with appropriate lymphadenectomy and adequate margins, both proximally and distally, to guard against local recurrence. Certain factors, such as mucinous tumors, microinvasion, and non-exophytic tumors of the rectum have been shown to have a propensity for local recurrence. Local treatment by fulguration or electrocoagulation is advocated only for tiny tumors confined to a polyp, or for the extremely elderly or poor-risk patient. Radiation therapy appears to be an appropriate adjuvant to the treatment of rectal cancer either preoperatively or postoperatively.

Aged↗

Squamous-cell carcinoma of the colon. Experience at the University of Chicago, review of the literature, report of two cases.

Primary squamous-cell and adenosquamous-cell carcinoma of the colon are uncommon and their characteristics not well known. This paper reports the clinical features and pathologic findings of two colonic adenosquamous carcinomas and reviews other reports of adenosquamous and squamous carcinoma of the colon from the English medical literature. Including these two cases, 63 cases have been reported since 1927. Of these, six occurred in patients with ulcerative colitis, three occurred at the colonic opening of chronic colocutaneous fistulas, and concomitant schistosomiasis was present in two patients. Synchronous squamous-cell carcinoma of the colon was present in 3.2 percent of cases and 10 percent had either antecedent, synchronous, or metachronous adenocarcinoma of the colon. These lesions appeared to be distributed uniformly throughout the colon. The five-year survival after resective therapy for primary squamous-cell and adenosquamous-cell carcinoma of the colon calculated with life table analysis is 50 percent for Dukes' B lesions, 33 percent for Dukes' C lesions, and 0 percent for Dukes' D lesions.

Actuarial Analysis↗

Adenosquamous-cell carcinoma in ulcerative colitis. Report of a case.

Three adenosquamous carcinomas and 2813 adenocarcinomas of the colon proximal to a line 7 cm craniad to the dentate line were treated between 1946 and 1986. Of these, one adenosquamous carcinoma and 42 adenocarcinomas were associated with ulcerative colitis. Therefore it was calculated that adenosquamous carcinoma occurs 0.07 percent as frequently as adenocarcinoma of the colon in the general hospital population and 2.4 percent as frequently in patients with ulcerative colitis, a 33-fold increase. It is concluded that, although adenosquamous-cell carcinoma of the colon is a rare tumor, its frequency in relation to adenocarcinoma increases in the presence of ulcerative colitis.

Adenocarcinoma↗

Ras oncogene expression as a prognostic indicator in rectal adenocarcinoma.

In order to investigate the value of ras oncogene expression as a prognostic indicator in rectal adenocarcinoma, we evaluated the level of ras gene protein product (p21) in the available material of 149 consecutive Dukes' B and C specimens resected at our institution between 1965 and 1981. Five year follow-up was available in all patients. Pathology slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis, study of histopathological features, and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution of antibody giving definitive staining using the avidin-biotin peroxidase method. The analysis indicated that the group of tumors with high (greater than or equal to 1:40,000) p21 titers had a worse 5-year survival (43.9 versus 64.3%, P less than 0.02), higher incidence of distant metastases (51.8 versus 23.2%, P less than 0.001), and more advanced Dukes' stage (53.7 versus 35.7% incidence of Dukes' C stage, P less than 0.04) than tumors with low (less than 1:40,000) titers. Multivariate analysis also demonstrated that the influence of the level of ras gene protein product on survival was independent of Dukes' stage. We conclude that detection of high levels of ras oncogene protein product indicates a group of tumors with a more aggressive behavior, characterized by a higher percentage of distant recurrences and worse prognosis. These findings suggest that measurement of p21 may become clinically important in identifying patients at high risk of recurrent disease.

Adenocarcinoma↗

A 5- to 21-year follow-up and analysis of 250 patients with rectal adenocarcinoma.

A total of 250 patients with rectal adenocarcinoma were operated on at the University of Chicago Medical Center between 1965 and 1981. The operation performed was curative resection in 154 patients, palliative resection in 16 patients, diverting colostomy in 21 patients, exploratory laparotomy in 11 patients, and transanal removal in 48 patients. Of the 154 curative resections, 115 were abdomino-perineal (APR), three were total proctocolectomies, and 36 were low anterior resections (LAR). No anastomotic complications were observed in this latter group. Operative mortality was 3%. Complete follow-up was obtained in 152 patients (98.7%). Five- and 10-year actuarial survival rates were 68.8 and 59.4%, respectively, for patients with Dukes' B1 adenocarcinoma (n = 32), 55.8 and 44.2% for Dukes' B2 tumors (n = 52), and 42.9% and 25.4% for Dukes' C tumors (n = 63). Distant metastases developed in 59 patients (39.6%), and pelvic recurrence developed in another 18 patients (12%); 5-year survival rates were 23.6% and 22.2%, respectively. Multivariate analysis with Cox regression showed that stage (p = 0.0001), race (p = 0.03), tumor morphology (p = 0.02), and vascular and/or lymphatic microinvasion (p = 0.001) were statistically significant in their association with survival. Logistic regression analysis confirmed these results and allowed for the estimation of 5-year survival probabilities in 16 groups of patients defined by various associations of these four factors. These estimates ranged from a high of 92% in Caucasian patients with Stage B, exophytic tumors with no vascular or lymphatic microinvasion, to a low of 14% in black patients with Stage C, nonexophytic tumors and with the presence of vascular and/or lymphatic microinvasion. Univariate analysis showed that histologic type (p = 0.0006), stage (p = 0.05) and vascular and/or lymphatic microinvasion (p less than 0.001) were significantly associated with the incidence of pelvic recurrence. Analysis of the extent of the operation revealed that the incidence of pelvic recurrence was reduced by the performance of a wide pelvic lymphadenectomy (9.4% vs. 16.4%), but the result did not reach statistical significance (p = 0.16). In conclusion, this study confirms the well-established prognostic value of the Dukes' staging classification of rectal carcinoma. Further, the analysis reveals that race, tumor morphology, and the presence or absence of lymphatic and/or vascular microinvasion significantly influence outcome. By associating these four statistically significant and independent variables, the prognosis for any individual patient can be estimated more precisely than by using Dukes' staging alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Surgical treatment of carcinoma of the abdominal colon.

Eighty-eight consecutive patients with invasive, but potentially curable, carcinoma of the abdominal colon were operated upon between January 1970 through June 1974 at the University of Chicago Medical Center by a small group of senior surgeons, all of whom utilized extensive lymphadenectomy. Pathologic stage of the disease, lymph node involvement, contiguous organ involvement and degree of differentiation of the primary tumor affected survival rates. Five and ten year absolute survival rates were 71.2 and 50.0 per cent, and the relative survival rates were 78.1 and 60.9 per cent. By five years, 30.0 per cent of the patients had recurrence, and by ten years, 33.3 per cent had recurrence. The majority of recurrences occurred within three years of operation. Only 12 per cent of the recurrences were local or regional. We conclude that operation using wide anatomic resection and extended lymphadenectomy improves survival rates and limits local and regional recurrences in patients with carcinoma of the abdominal colon. Furthermore, surveillance of patients after operation for invasive carcinoma of the abdominal colon should be aggressive for at least the first three years because of the frequency of recurrence within this period.

Adenocarcinoma↗

Importance of tumor morphology for the long term prognosis of rectal adenocarcinoma.

A retrospective review of 149 consecutive potentially curable rectal adenocarcinomas operated on at our institution between 1965 and 1981 was carried out to assess whether tumor morphology influences long term survival. Complete follow-up was available on all patients and extended to 20 years. Data on tumor morphology was extracted from pathology reports and was available in 147 cases (98.6%). Tumors were defined as exophytic (n = 76) when exhibiting a polypoid growth pattern protruding into the lumen at least 1 cm; when lacking such characteristic growth pattern, tumors were classified under the general term of nonexophytic (n = 71). The 5 year survival rate calculated with life table analysis was 80 per cent for exophytic carcinomas and 54.1 per cent for nonexophytic tumors. This difference was verified by logistic regression analysis and proportional hazard technique and is statistically highly significant (P = 0.001). The rate of distant metastases was 29.7 per cent for exophytic adenocarcinoma and 48.6 per cent for nonexophytic tumors (P = 0.02). Although the results did not reach statistical significance, local recurrence of tumor occurred about twice as often in nonexophytic tumors (15.7%) compared with exophytic tumors (8.1%). Thus, we conclude that tumor morphology is an important preoperative prognostic factor for survival and prediction of distant metastasis, and possibly for local recurrence.

Actuarial Analysis↗

Ras oncogene p21 levels parallel malignant potential of different human colonic benign conditions.

Ras oncogenes are a specific family of genes believed to play a role in malignant transformation and tumor growth in humans. To gain a better understanding of the role these oncogenes may play in malignant transformation, we evaluated the levels of a ras gene protein product (p21) in formaldehyde-fixed, paraffin-embedded specimens of normal human colonic mucosa, hyperplastic polyps, tubular adenomas, villous adenomas, and epithelium from a patient with ulcerative colitis. The p21 protein content was measured using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. The titer value was expressed as the highest dilution of antibody giving definite staining using the avidin-biotin peroxidase method. Differences in p21 titer values among all classes of polyps were significant (hyperplastic polyps values were less than tubular adenomas values, which were less than villous adenoma values). The p21 titers obtained from ulcerative colitis specimens were similar to those obtained from villous adenomas. We conclude that the levels of ras oncogene protein product increase with the malignant potential of benign human colonic conditions. These findings suggest that the ras oncogene protein product may play an important role in the malignant transformation of benign lesions of the human colon. If these findings are confirmed, as technology progresses to allow molecular probes to measure gene products in biopsy specimens, high-risk patients could be monitored and treated before actual malignant transformation occurs.

Adenoma↗

A technique for hepaticodochojejunostomy with transhepatic stent.

A technique for the placement of a transhepatic stent at the time of biliary-enteric anastomosis, which prevents the stent from interfering with the performance of the anastomosis is described herein. This technique obivates the need to pass the transhepatic catheter after the posterior portion of the hepaticojejunostomy has been completed.

Hepatic Duct, Common↗

Enterovesical fistula complicating Crohn's ileocolitis.

An enterovesical fistula, an infrequent complication of Crohn's ileocolitis which is considered to constitute a difficult surgical problem, was encountered in 29 patients. These patients had been treated for Crohn's disease by medical means for years and several had previously undergone bowel resections. An exacerbation of the Crohn's disease occurred in all patients coincident with the appearance of dysuria or the obvious clinical presentation (fecaluria) of the fistula. Other manifestations of active Crohn's disease frequently coexisted. Radiographic evaluation was of limited help in establishing the presence of the fistula. Cystoscopy was suggestive of the diagnosis in 18 of 20 patients so examined. Treatment consisted of ileocecal resection with primary anastomosis (25) or exteriorization (4). The bladder defect was sparingly excised and closed with absorbable sutures. One patient developed a bladder leak which closed spontaneously. Recovery was uneventful in the others. An ileovesical fistula constitutes an indication for operation not only to eradicate the urinary sepsis but also to correct the other complications (malnutrition, obstruction, abscess) of Crohn's disease. To assure an uncomplicated course, emphasis must be placed on an individually designed correct approach to the (causative) intestinal problem, while the surgical aspects of the bladder defect can be a matter of routine.

Abscess↗

The physiologic effects of ileal reservoirs and efferent conduits complementing ileoanal anastomosis: an experimental study in dogs.

S-shaped ileal reservoirs (SSRs) and double-barreled ileal reservoirs (DBRs) of equal size were placed 6 or 2 cm from the anus and evaluated over 1 year for their ability to improve the functional incontinence noted after an ileoanal anastomosis (IAA). Compared to straight IAA, both reservoirs prolonged intestinal transit (235 minutes versus 135 minutes, P less than 0.001) and alleviated frequency without causing nutritional abnormalities. The capacity of the reservoirs was greater than that of a comparable length of distal ileum in dogs (n = 6) with straight IAA (304 +/- 16 ml versus 102 +/- 2 ml, P less than 0.001). The SSRs (n = 9), in contrast to the DBRs (n = 10), developed excessive volume capacity (360 +/- 30 ml versus 254 +/- 104 ml, P less than 0.01) and obstructive complications. Reservoirs with 6 cm efferent conduits (n = 13), in contrast to those with a 2 cm efferent conduit (n = 6), underwent marked dilatation (334 +/- 24 ml versus 238 +/- 13 ml, P less than 0.005). Electromyography and manometry revealed the DBRs to be more contractile than the SSRs but less than ileum proximal to the anus in dogs with a straight IAA. Ileal reservoirs improve results after IAA. Reservoirs should be complaint and yet contractile (e.g., DBR) so as to discourage excessive dilatation, which is the harbinger of obstruction. Ileal conduits facilitate reservoir placement, but if longer than 2 cm they excessively impeded reservoir emptying, predisposing to excessive reservoir dilatation and obstruction. A DBR with a 2 cm efferent conduit results in continence without obstructive problems.

Absorption↗