Biomedical subjects

F Michelassi

Publications and source records attributed to F Michelassi.

At least 73 records · Page 4Linked to original sources

PubMed1990

Local recurrence after curative resection of colorectal adenocarcinoma.

A total of 853 patients with 861 colorectal adenocarcinomas were operated on at our institution between 1965 and 1981. Complete follow-up information was obtained in all but six patients (99.4%), and all available histologic slides were reviewed to determine pathologic stage and characteristics. Six hundred fifty-one patients (76.3%) underwent a potentially curative procedure, and their operative mortality rate was 2.8%. Of the 627 patients available for analysis, 50 (8%) had a local recurrence. The median time to local recurrence was 18 months, and only 16% of local recurrences were diagnosed 5 years after the original resection. Median survival of patients with a local recurrence was 3 1/2 years from the original resection, and 16 patients (32%) survived 5 years or longer. A multivariate logistic regression analysis was conducted to examine the influence of several clinical and pathologic characteristics on local recurrence among Dukes' stages B and C adenocarcinomas (n = 539) after exclusion of patients with synchronous tumors (n = 8), postoperative deaths (n = 18), loss to follow-up (n = 6), or incomplete data (n = 11). This analysis revealed that the local recurrence rate was significantly related to depth of invasion (B1 + C1 = 0%; B2 + C1 = 10%; p less than 0.01), site of origin (right plus transverse colon = 6%; left plus rectosigmoid colon = 10%; rectum = 12%; p less than 0.05), and lymphatic or capillary microinvasion (absent, 6%; present, 14%; p less than 0.05). This analysis attempts to identify patients at high risk for development of local recurrent disease to select candidates for postoperative adjuvant therapy.

Adenocarcinoma↗

PubMed1990

Relationship between ras oncogene expression and clinical and pathological features of colonic carcinoma.

In order to investigate the value of ras oncogene expression as a prognostic indicator in colonic adenocarcinoma, we evaluated the level of ras gene protein product (p21) in the available material of 109 surgical specimens resected at our institution between 1978 and 1981. Pathology slides and archived paraffin blocks were retrieved for confirmation of the original diagnosis, determination of stage, 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 given definitive staining using the Avidin-Biotin peroxidase method. The analysis indicated that tumors with high (greater than or equal to 1:40,000) p21 titer had a lower five-year survival rate than tumors with low (less than 1:40,000) titers (34.3% vs 60.8%, p less than 0.02). When a logistic regression analysis was used with the dependent variable being five-year survival and the independent variables being age, sex, location of tumor. Dukes' stage, mucin production, p21 titer, differentiation degree and tumor size, the statistically significant relationship of the level of ras gene protein product to long-term survival was negated by the concomitant knowledge of Dukes' stage. On the other hand, when only the variables available in the preoperative period were entered in the multivariate analysis, p21 titers retained a significant relationship with long-term survival (p less than 0.05). We conclude that ras oncogene determination in colonic carcinomas may have clinical importance for the pre-operative identification of a group of colonic tumors with a more aggressive behavior and a poorer prognosis.

Adenocarcinoma↗

PubMed1990

Bullet emboli to the systemic and venous circulation.

The rarity of bullet emboli leads to frequent delays in diagnosis and inadequate early management. Our recent experience with this entity is described, and 153 cases reported in the English-language literature are reviewed and summarized. The majority of cases occurs as a consequence of civilian violence among men in their 20s and 30s. Most bullet emboli follow the direction of blood flow, although 15% of venous bullets cause embolization in a retrograde manner. One in 10 arterial emboli follow a right-heart or venous injury. Arterial bullets are symptomatic in 80% of cases, venous bullets in only one third. The choice of surgical management must be individualized according to the symptoms caused by the bullet and its location in the vascular system. In general, arterial bullet emboli are removed because of symptoms or findings of acute peripheral ischemia. Arterial and venous emboli not causing symptoms should be removed according to the risk of possible displacement and further embolization. Selective intraoperative angiograms and phlebograms can precisely localize the migrating bullet and permit appropriate placement of incisions before removal.

Adult↗

PubMed1989

Humoral hypercalcemia complicating adenosquamous carcinoma of the proximal colon.

Hypercalcemia as a complication of carcinoma of the colon is uncommon (1). It usually occurs in the presence of anorectal or rectal carcinoma that metastasizes to the lumbosacral vertebrae (2-4). Hypercalcemia complicating colon carcinoma in the absence of bone metastases--so-called humoral hypercalcemia of malignancy or paraneoplastic hypercalcemia--is rare. Only two such cases associated with adenocarcinoma of the colon (5,6) and two cases associated with adenosquamous carcinoma of the distal colon (rectum and sigmoid) (7) have been reported. We describe the first reported case of an adenosquamous carcinoma of the cecum and ascending colon that was accompanied by severe humoral hypercalcemia. The hypercalcemia was associated with a parathyroid hormone (PTH)-like substance.

Adenocarcinoma↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

Chromosome 5 allele loss in human gastric, ampullary and pancreatic carcinomas.

Chromosome 5 allele loss is a genetic alteration occurring during the multistep progression of colon carcinogenesis. To determine whether a similar genetic alteration occurs in other gastrointestinal malignancies, the authors have analyzed DNA extracted from freshly frozen normal and neoplastic tissue from nineteen patients who underwent radical resections for gastric, ampullary and pancreatic adenocarcinomas at the University of Chicago. Loss of heterozygosity for alleles on the long arm of chromosome 5 was detected in tumor DNA compared to normal tissue DNA from the same patient using restriction fragment length polymorphisms (RFLPs). Eleven patients were informative using the restriction endonuclease TaqI to generate RFLPs for chromosome 5 probes C11 P11 and pTP5E. Loss of heterozygosity was found in one of eight informative gastric carcinomas (12.5%) and in one of two informative ampullary carcinomas. The only informative pancreatic adenocarcinoma was heterozygous. It is concluded that chromosome 5 allele loss occurs in a variety of gastrointestinal malignancies and suggest that common genetic origins may underlie these different tumors.

Adenocarcinoma↗

PubMed1989

Nuclear morphometric measurements in rectal adenocarcinoma cells of patients of different races.

The reasons for the different long-term prognoses of black and white patients following curative resection of a rectal adenocarcinoma are unknown. In order to investigate whether rectal adenocarcinomas in blacks have clinical or pathologic characteristics that are different from rectal adenocarcinomas in whites, 149 patients with potentially curable rectal cancers resected at the University of Chicago Medical Center between 1965 and 1981 were retrospectively analyzed. Clinical records, pathology reports and pertinent slides were reviewed in each case. In 142 cases, enough histologic material was available to perform nuclear photometric measurements and determinations of DNA content by the slide-cytophotometric method. There was no difference between black and white patients in the stage, differentiation degree, morphology and ploidy of the tumors, or in the presence of microinvasion, metastases and mucin production. However, adenocarcinoma cells of black patients had smaller nuclei than did the corresponding nuclei of white patients (54.7 +/- 2.34 sq microns versus 58.9 +/- 1.84 sq microns; P less than .05), and the neoplastic nuclei of black patients were significantly rounder and more regular than the nuclei of white patients (mean roundness factors of 1.1 +/- 0.003 vs. 1.11 +/- 0.005; P less than .05). Although these findings will require confirmation from other large clinical series, they suggest that the different prognoses of black and white patients after curative resection of a rectal adenocarcinoma may be explained by a different tumor behavior intrinsically related to different karyotypic characteristics of the neoplastic cells.

Adenocarcinoma↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

Lymphatic smooth muscle responses to leukotrienes, histamine and platelet activating factor.

Regional lymphatics regulate the accumulation of edema resulting from inflammation. The effects of mediators of inflammation on lymphatic smooth muscle, the primary determinant of lymph flow, are poorly understood. We studied mesenteric lymphatic vessels in 22 anesthetized rats with in vivo videomicroscopy following topical applications of histamine, leukotriene C4 or D4, or platelet-activating factor (PAF). Diameter, contractility, and contraction frequency were measured, and flow was calculated. Histamine caused increases in vessel diameter and contractility (174 and 218% of control, respectively; P less than 0.05), while contraction frequency was unaffected. Leukotrienes C4 and D4 caused an increase in frequency of contraction (348 and 392% of control, respectively; P less than 0.05), while having no significant influence on diameter or contractility. PAF caused smooth muscle relaxation, resulting in vasodilation and a decrease in contraction frequency (202 and 5% of control, respectively; P less than 0.05). Topical application of histamine and leukotrienes caused significant increases in calculated flow, while PAF decreased calculated flow. Mediators of inflammation have striking and diverse effects on lymphatic smooth muscle activity.

Administration, Topical↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1987

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↗

PubMed1987

Effect of histamine and histamine receptor antagonists on rat mesenteric microcirculation.

Histamine release adjacent to mesenteric arterioles under conditions of ischemia causes vasodilation and increases regional blood flow. This is presumably a protective mechanism which may be blocked by the use of H1 and H2 antagonists. Mesenteric arterioles of 29 rats were observed with intravital microscopy. Diameter and erythrocyte velocity were measured and arteriolar flow was calculated. Histamine was topically applied to the vessels under view in sequentially increasing concentrations (10(-7) to 10(-4) M). Following systemic injection of an H1 or H2 receptor antagonist or ibuprofen, the application of 10(-4) M histamine was repeated. Topical histamine caused vasodilation (122% of control; P less than 0.05) at 10(-4) M with a corresponding increase in erythrocyte velocity and calculated flow (118 and 177% of control, respectively; P less than 0.05 for each). The vasodilatory effects of histamine were blocked by systemic injection of histamine receptor antagonists (H1 + H2 greater than H1 greater than H2), while ibuprofen had no significant effect. In situations in which the gut is at risk for ischemia, the use of H1 and/or H2 receptor antagonists may seriously compromise the mesenteric microcirculation.

Animals↗

PubMed1987

Effects of leukotrienes B4, C4, and D4 on rat mesenteric microcirculation.

Arachidonic acid is metabolized to leukotriene (LT) B4, C4, D4, and E4 by lipoxygenase. LTB4 is a chemotactic agent while LTC4 and LTD4 stimulate smooth muscle fibers to contract. Mesenteric vessels have the capacity to release leukotrienes. The possibility that leukotrienes might be responsible for or contribute to mesenteric ischemia during mesenteric low flow, embolism, and thrombosis prompted us to investigate their action on mesenteric vessels. LTB4, C4, and D4 were applied topically on small bowel mesentery of 22 Sprague-Dawley rats in sequentially increasing concentrations. Mesenteric arterioles with diameters of 8-20 microns were observed through a microscope and vessel diameters were measured using a video shear monitor. LTB4 had no effect on diameter, but doses as low as 3 X 10(-8) M induced white blood cell adherence to venular endothelium, reflecting the potent chemotactic properties of this compound. LTC4 and D4 had no effect on systemic blood pressure or white blood cell adherence. Applications of 6.4 X 10(-9), 3.2 X 10(-8), and 6.4 X 10(-8) M LTC4 decreased mesenteric arteriolar diameter to 85.3* +/- 4.7% (mean +/- SD), 75.7* +/- 7.5%, and 66.8* +/- 6.1% of baseline, and 4 X 10(-9), 2 X 10(-8), and 4 X 10(-8) M LTD4 decreased diameter to 84.9* +/- 6.1%, 75.1* +/- 4.2%, and 64.1* +/- 5% of baseline, respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗

PubMed1987

Survival in 1001 patients with carcinoma of the pancreas.

Among 1001 patients with carcinoma of the pancreas, 23 of 912 patients with exocrine carcinomas, 10 of 46 with ampullary carcinomas, and 21 of 43 with malignant islet cell tumors survived 3 years. Of the survivors with exocrine cancers, there were nine of 97 patients who had curative operation, two had had palliative resections only, and one was an incidental microfocal carcinoma; in the remaining 11 patients a histologic origin in the pancreas was not established. Preoperatively suspected and histologically proven 3-year survivors included six patients with ductal adenocarcinomas, three patients with mucinous cystadenocarcinomas, one patient with acinic cell carcinoma, and one patient with microadenocarcinoma. Only two patients can be considered cured. Tumor size and lymph node status did not correlate with survival. Cystadenocarcinomas comprised 1% of cases but one third of 3-year survivors. Long-term survival in histologically confirmed pancreatic carcinoma is a rare event that cannot be predicted in the individual case.

Aged↗