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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 109 records · Page 6Linked to original sources

Dietary epidemiology of cancer of the colon in western New York.

The authors interviewed 428 pathologically confirmed cases of colon cancer and controls matched on age, sex, race, and neighborhood in the New York counties containing the cities of Buffalo, Niagara Falls, and Rochester. Risk of colon cancer in both males and females, studied separately, appeared to increase with the amount of total fats and total calories ingested. In addition, we found the risk to increase with increases in the Quetelet index of relative weight (weight (kg)/height (m)2). Dietary fiber was only equivocally associated with risk. Fats and Quetelet index were associated with increased risk in a regression analysis adjusting each factor for the other, as well as for fiber, age, and socioeconomic status. The same was true for calories and Quetelet index. Future efforts to clarify a possible protective role for fiber and to disentangle the effects of fats and calories need to be undertaken. The fact that calories ingested and obesity are each associated with increased risk suggests the importance of studying calorie expenditure.

Body Height↗

ECOG phase II trials of MGBG, chlorozotocin, COM multidrug therapy in advanced measurable colorectal cancer.

The Eastern Cooperative Oncology Group (ECOG) entered 326 patients with advanced measurable colorectal cancer into four phase II drug or drug combination trials. Previously treated and chemotherapy-naive patients were eligible. Chlorozotocin was administered to 83 patients (51 previously treated), methyl-glyoxal-bis-guanylhydrozone (MGBG) to 90 patients (58 previously treated), and two regimens of the three-drug combination of cyclophosphamide, vincristine, and methotrexate (COM) to 153 patients (120 previously treated). The multidrug regimen had been developed specifically for previously treated patients. In this trial, chemotherapy-naive patients were no more likely to respond than were members of the previously-treated group. Even among previously untreated patients, response rates did not exceed 10% in any of these phase II programs. They are not recommended for further trials in patients with colorectal cancers.

Adenocarcinoma↗

Colorectal villous and tubulovillous adenomas equal to or greater than four centimeters.

The records of 237 patients treated for benign and malignant villous and tubulovillous adenomas at Roswell Park Memorial Institute from 1963 to 1987 were reviewed. Sixty-five adenomas were greater than or equal to 4 cm and form the basis of this report. Fifteen (23%) were in the cecum, 3 (5%) in the right colon, 1 (1%) in the splenic flexure, 10 (15%) in the sigmoid colon, and 36 (55%) in the rectum. The most common symptoms were rectal bleeding (70%), mucus diarrhea (44%), constipation (22%), and tenesmus (19%). Fifty-five (85%) of these large adenomas contained invasive adenocarcinoma and one in situ carcinoma. Two thirds of invasive carcinomas arose from predominantly villous adenomas and one third from tubulovillous adenomas. Half of all malignant adenomas demonstrated metastases to regional lymph nodes or distant metastases. Seven malignant adenomas (12%) were associated with synchronous adenocarcinomas of the colon, and 29% of malignant adenomas were associated with synchronous adenomatous polyps, principally tubular type. Four of nine benign, large adenomas were associated with synchronous adenomas but with no adenocarcinomas. No relationship was found between the size of the adenoma, location, or Dukes' stage. Though the incidence of in situ and invasive carcinomas is clearly related to the size of the adenoma, a linear relationship could not be demonstrated.

Adenocarcinoma↗

Protein A immunoadsorption in the treatment of malignant disease.

Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.

Adolescent↗

Squamous cell carcinoma antigen as a marker for squamous cell carcinoma of the anal canal.

Twenty-one patients with documented squamous cell carcinoma (SCC) of the anal canal underwent prospective serial collection of 101 serum samples for radioimmunoassay of SCC antigen to evaluate regression or progression of disease. Eighteen presented with primary SCC of the anal canal, two with metastatic disease, and one with a recurrence in the perineum. Median follow-up was 18 months. Thirteen of 22 serum samples were true-positives, and nine of 22 were false-negatives. Four of 79 serum samples were false-positives and 75 of 79 were true-negatives. The sensitivity of this test is 59% and the specificity is 95%, with the accuracy of a positive test being 76%.

Adult↗

Plasma and tumor tissue pharmacology of high-dose intravenous leucovorin calcium in combination with fluorouracil in patients with advanced colorectal carcinoma.

Plasma pharmacokinetics of high-dose (500 mg/m2) leucovorin calcium (dl-5-formyltetrahydrofolic acid [dl-CF]) and fluorouracil (FUra) have been evaluated in patients with advanced colorectal cancer treated with the combination of FUra and dl-CF by two different intravenous (IV) schedules: (A) In patients with no prior chemotherapy, dl-CF was administered by a two-hour IV infusion and FUra by rapid IV injection one hour after the start of the dl-CF infusion and (B) in previously treated patients, dl-CF and FUra were administered by five-day continuous IV infusion (CI). Following the two-hour infusion of dl-CF, mean peak plasma concentration and elimination half-life of I-5-formyltetrahydrofolic acid (I-CF) were 24 +/- 6 mumol/L and 0.8 +/- 0.1 hour, respectively. CI of dl-CF over five days yielded a mean steady-state plasma level of I-CF of only 1.2 +/- 0.5 mumol/L. Peak and steady-state plasma concentrations of the metabolite 5-methyl tetrahydrofolic acid were comparable in the two schedules (17 +/- 8 mumol/L for the two-hour infusion and 12 +/- 5 mumol/L for the CI). Areas under the concentration v time curve (AUC) of total reduced folates were significantly greater under conditions of CI: 89.0 v 16.7 mmol/L/min for the two-hour infusion. In tumor tissue, 5,10-methylenetetrahydrofolate increased eight-fold two to four hours following the two-hour infusion and two-fold during the CI of dl-CF and FUra. Inhibition of thymidylate synthase (dTMP-S) by the two-hour and CI infusion schedules were 66% v 39%, respectively. The observed differences in the intracellular dTMP-S folate cofactor pools and the degree of inhibition of dTMP-S achieved in patients treated by two different schedules may be due to differences in the biochemical properties and/or to differences in the modulation of FUra metabolism by folate of tumor tissues obtained from newly diagnosed and previously treated patients.

Antineoplastic Combined Chemotherapy Protocols↗

Adenocarcinoma of the appendix.

Sixteen instances of adenocarcinoma of the appendix treated at Roswell Park Memorial Institute between 1964 and 1986 were reviewed. Thirteen of 15 were mucinous and ten were well differentiated. Synchronous metastases were present in 11 patients, with carcinomatosis being the most common pattern of metastases (nine patients). Seven of eight women had ovarian metastases. Nine of the 11 patients with metastatic disease presented with complaints referrable to the metastatic site. The five year survival rate was 50 per cent in the eight patients who underwent right hemicolectomy and 25 per cent in the four patients who underwent appendectomy. The data from this review support right hemicolectomy as the treatment of choice for adenocarcinoma of the appendix. The prolonged survival time of patients with metastatic disease and the symptomatic nature of that disease support the application of palliative oophorectomy in patients with ovarian metastases.

Adenocarcinoma, Mucinous↗

Life-threatening toxicity of cancer therapy.

The use of chemotherapeutic agents in the therapy of cancer has led many physicians to increase the dose of these agents in the hopes of increasing efficacy. Increasing dosages caused an increase in the toxicity, which was occasionally life threatening and required aggressive therapeutic measures.

Antineoplastic Agents↗

Amsacrine with high-dose cytarabine is highly effective therapy for refractory and relapsed acute lymphoblastic leukemia in adults.

Thirty-six patients with relapsed acute lymphoblastic leukemia (ALL) and four with primary refractory ALL were treated with a regimen that included amsacrine, 200 mg/m2, intravenously daily for three days with cytarabine, 3 gm/m2, by infusion over three hours daily for five days. There were 27 remissions in the 36 relapsed patients and two in the four patients with primary refractory disease. Seventeen of the 23 patients with common ALL, four of the six with T-cell ALL, one of the three with B-cell ALL, and seven of eight whose cells were not characterized responded. Toxicity of this regimen was comparable to other reinduction regimens for ALL, but the side effects characteristic of high-dose cytarabine therapy were absent. Since these results compare favorably with conventional induction regimens, its use in the primary treatment of adults and children with high-risk ALL is proposed.

Adolescent↗

Follow-up colonoscopy in patients with colorectal adenomatous polyps.

Multiple follow-up colonoscopies were performed in 44 asymptomatic patients after polypectomy of colorectal adenomatous polyps. Twenty-six patients (59%) developed new adenomatous polyps. In 81% the new polyps were located in the same segment of the colon where a previous polyp had been totally removed. Polyps removed during follow-up, compared with the initial polyps, revealed significantly more benign and smaller polyps. The number of initial polyps together with occurrence of atypia were factors determining a short time interval for developing new adenomatous polyps. The mean time for developing a 5-mm or larger polyp was significantly longer than polyps less than 5 mm in diameter.

Adenoma↗

Selenium status and the polyp-cancer sequence: a colonoscopically controlled study.

Diminished blood selenium levels have been associated with increased risk of gastrointestinal cancers in man, while dietary selenium supplementation reduces the incidence of experimental colon cancer in rats. However, no previously published data are available concerning selenium and the evolution of colon cancer from benign neoplastic colonic polyps through localized and metastatic cancer. To assess any influence of selenium on this polyp to cancer sequence, we measured plasma and erythrocyte selenium levels in colonoscopically and histologically evaluated patients with adenomatous polyps (group I), locally resectable colon cancer (group II), metastatic colon cancer (group III), and selected colonoscopy negative controls (group IV). We found no difference in selenium levels between groups IV versus groups I or II. Likewise, within group I, no difference in selenium was present for different polyp histologies or numbers of polyps. However, selenium levels did drop progressively (p = 0.028, ANOVA) from polyp (group I) to local cancer (group II, p = NS vs group I) to metastatic cancer (group III, p less than 0.05 vs group I or group II). Parallel changes were seen in both plasma and erythrocyte levels, suggesting that these selenium abnormalities are of long duration, reflecting tissue stores, and therefore capable of influencing cancer risk. We conclude that selenium stores may not be an important factor in the de novo formation of benign neoplastic colonic polyps. Although these data suggest that selenium does not affect the polyp-cancer sequence, it is possible that a subset of patients with polyps and the lowest selenium levels are at higher risk for malignant transformation. However, these human data do not support a significant role for selenium in colon carcinogenesis.

Aged↗

Expression of an unusual isozyme of lactate dehydrogenase in the serum of cancer patients and comparison with carcinoembryonic antigen.

Two studies reported here demonstrate a statistically significant association between metastatic cancer and the appearance of the k isozyme of lactate dehydrogenase in serum of affected patients. The first study included 190 coded samples from three types of cancer patients and matched controls; the second included 155 preoperative and 200 postoperative colorectal cancer patients. In the second, plasma carcinoembryonic antigen was compared with serum k isozyme of lactate dehydrogenase as an indicator of the presence of metastatic cancer. This comparison showed that both markers were independently useful for assessing patient status and predicted that a combination of the two should be a better discriminator for the presence of metastases than either marker alone.

Biomarkers, Tumor↗

Polyamine biosynthetic activity in normal and neoplastic human colorectal tissues.

Polyamine biosynthetic activity was assessed in various colorectal tissue samples consisting of noninvolved mucosa, benign adenomatous polyps and adenocarcinomas taken at surgery from a total of 40 patients. Ornithine decarboxylase (ODC) displayed a gradient of enzyme activity (i.e., adenocarcinoma greater than polyps greater than mucosa) which seemed to correlate positively with the neoplastic status of the tissue. In 10 of the patients, samples were obtained for all three tissue types. Five of these exhibited a clear repetition of the trends in enzyme activity seen with the mixed patient tissue sampling whereas the remainder differed by having the highest ODC activity in the polyps. In nine of the ten cases, ODC activity was substantially lower in the mucosa than in either of the neoplastic lesions. Trends in enzyme activity were the same for tissues obtained from either the colon or rectum. The ODC activity in adenocarcinomas could not be correlated with histologic differentiation, stage or site of the disease, however, in samples from female patients (all postmenopausal) the activity was elevated over normal mucosa to a greater extent (ten-fold) than in male patients (seven-fold). S-adenosylmethionine decarboxylase activity was assessed in 27 of the 40 patients and found to follow the same distribution as ODC; however, the mean value differences +/- SEM between tissues were less distinct. In general, tissue polyamine pool analysis of these same specimens reflected the levels of ornithine and S-adenosylmethionine decarboxylase activities. Overall, the data reveal an increase in polyamine biosynthetic activity in colorectal neoplasms, relative to surrounding mucosa, which may correlate with (1) progression of the neoplastic process, (2) the proportion of proliferating cells, (3) the rate of cell proliferation, or (4) a combination of two or all of these possibilities.

Adenocarcinoma↗

Malignant lymphomas in a population at risk for acquired immune deficiency syndrome.

Certain neoplasia are closely associated with acquired immune deficiency syndrome (AIDS). To evaluate this relationship the authors reviewed the occurrence of lymphomas in populations at high risk for AIDS; the study population included prisoners from New York State and nonprisoner intravenous drug abusers (IVDA). Non-Hodgkin's lymphoma was diagnosed in 16 prisoners, all of whom were IVDA, and four nonprisoner IVDA. The observed number of prisoners with non-Hodgkin's lymphoma (11) diagnosed between January 1, 1981 and December 12, 1984, significantly greater than the expected number (2.28) based on age adjusted incidence rates for the US population (P less than 0.001). The calculated average incidence rate for non-Hodgkin's lymphoma among New York State prisoners aged 20 to 49 years was 21.5/10(5) to 67.2/10(5), which was nearly sixfold to 18-fold higher than the general population. For prisoner IVDA, specifically, this incidence may be as high as 164/10(5), which represents a 40-fold increase in the relative risk compared with the general population. It is concluded that, non-Hodgkin's lymphoma is frequently a manifestation of AIDS among IVDA, and is the most common malignancy seen in IVDA with AIDS.

Acquired Immunodeficiency Syndrome↗

Preoperative cystoscopic findings in resectable rectal adenocarcinoma.

Forty-nine patients underwent preoperative cystoscopy prior to surgical resection for adenocarcinoma of the rectum. There were 30 men and 19 women ranging in age from 26 to 78 years, with a median age of 59 years. Surgical resections consisted of abdominoperineal resection, posterior exenteration, or total pelvic exenteration. Twenty patients had positive findings on preoperative cystoscopy while 29 had negative findings. Of the 20 patients with positive cystoscopic findings, eight (40%) had either urologic symptoms or abnormal microscopic findings on urinalysis; however, only one of these eight patients had tumor invasion of the bladder wall at cystoscopy, while the remaining seven had associated benign conditions. In the 29 cystoscopy procedures in which findings were negative, only three patients (10%) had urologic symptoms or abnormal results of urinalysis, none of which were secondary to the rectal carcinoma. We conclude that urinary symptoms can be misleading and unreliable when predicting neoplastic involvement of the bladder by carcinoma of the rectum because of the high incidence of associated benign disorders of the bladder. Therefore, cystoscopy does not have a useful role in staging patients undergoing surgery for rectal carcinoma in terms of local tumor extension.

Adenocarcinoma↗

Metastases in small lymph nodes from colon cancer.

Lymph node metastases are important determinants in the prognosis of primary colorectal cancer. Although it has been established that enlarged, palpable lymph nodes contain metastases in less than half of the cases, no definitive data concerning the incidence of metastases in lymph nodes measuring 5 mm or less are available. We treated the surgical specimens of 52 consecutive patients who had colon cancer with a lymph node clearance technique at the Roswell Park Memorial Institute, Buffalo. We found 2699 lymph nodes in the 52 specimens, with a mean of 52 lymph nodes per specimen (range, five to 151). Sixty-four lymph nodes were found with metastases in 21 (40%) of the 52 patients. Fifty-nine of 64 of the lymph nodes were reexamined and remeasured. Thirty-nine lymph node metastases measured less than 5 mm, 13 were between 5 and 10 mm, and eight were larger than 10 mm. We concluded that lymph node metastases in colon cancer occur most frequently in lymph nodes measuring less than 5 mm (small lymph nodes). The use of lymph node clearing techniques in surgical specimens improves detection of small lymph node metastases and thereby diminishes understaging.

Colonic Neoplasms↗