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Biomedical subjects

L Herrera

Publications and source records attributed to L Herrera.

At least 145 records · Page 8Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Angiotensin II (AII) and adrenocorticotropin release: modulation by estradiol of the AII biological activity and binding characteristics in anterior pituitary dispersed cells.

The present studies were designed to test if estrogens influence basal and angiotensin II (AII)-stimulated ACTH release and the binding characteristics of AII receptors in isolated anterior pituitary (AP) cells from estrogen-deplete and estrogen-replete rats incubated in vitro. AP cells were obtained from various adult donors: randomly cycling (rc), 10-day ovariectomized (Ovx), Ovx with estradiol restored at a circulating physiological level (Ovx + lEB), Ovx with estradiol at a supraphysiological circulating level (Ovx + hEB); and male (m) rats. The amount of ACTH released under basal conditions was similar in the rc, Ovx + lEB, and m groups, although this amount was significantly greater (P less than 0.02) than that in the Ovx and Ovx + hEB groups. The ACTH-releasing activity (CRA) of AII was concentration dependent (10(-9)-10(-6) M) in all cells. The rank order of the CRA of AII in the groups varied as follows: rc = Ovx + lEB greater than Ovx = Ovx + hEB = m. The slopes of the AII responses were similar. Estradiol addition in vitro did not modify either basal or AII-stimulated ACTH release in any group of cells. AII binding studies indicated that AP cells from donors with different circulating estradiol levels had similar apparent equilibrium dissociation constants (Kd, 16-30 nM). However, the maximum binding capacities in AP cells from the m, Ovx, and Ovx + hEB groups (40, 51, and 49 fmol/10(6) cells, respectively) were significantly lower (P less than 0.05) than those in the rc and Ovx + lEB groups (77 and 81 fmol/10(6) cells, respectively). In summary, these studies indicate that 1) circulating levels of estradiol are able to modulate spontaneous ACTH release by dispersed AP cells; and 2) circulating estradiol, at a lower or higher level than that during the estrous cycle, decreases the in vitro ACTH-releasing activity of AII, possibly through a reduction in the number of AP AII receptors. These results further suggest that estrogen is likely to have a physiological role in corticotropic function.

Adrenocorticotropic Hormone↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

The value of colonoscopic surveillance after curative resection for colorectal cancer or synchronous adenomatous polyps.

Between 1975 and 1984, 270 patients underwent a potentially curative resection for colorectal carcinoma. One hundred eighty-eight patients (70%) underwent preoperative colonoscopy, of which 129 patients (69%) were followed up with at least two postoperative colonoscopies. In 91 patients (70%), preoperative colonoscopy revealed no synchronous adenomatous polyps or cancer. Synchronous adenomatous polyps were found in 35 patients (27%), and three patients (2.3%) had a synchronous invasive cancer. Nineteen (54%) of the 35 patients with synchronous adenomatous polyps developed metachronous adenomatous polyps during the follow-up period compared with 24 (26%) of 91 patients without synchronous adenomatous polyps. The median interval to the development of metachronous adenomatous polyps was 19 months, and all of these polyps were 1 cm or less in size. Patients with synchronous adenomatous polyps less than 30 cm from the primary lesion (68%) developed metachronous polyps more often than did patients whose synchronous adenomatous polyps were more than 30 cm from the primary lesion (37%). Preoperative colonoscopy is important for determining synchronous pathology and identifying patients at risk for metachronous polyps.

Adult↗
PubMed1987

Synchronous and metachronous colon lesions in squamous cell carcinoma of the anal canal.

The charts of 79 patients with a histologic diagnosis of squamous cell carcinoma of the anal canal were reviewed to determine the incidence of synchronous and/or metachronous colon lesions. Forty-six patients underwent an adequate preoperative evaluation of the colon and rectum. Ten patients underwent colonoscopy, 33 patients underwent a barium enema, and three patients underwent colonoscopy and a barium enema. In this group six adenomatous polyps and three hyperplastic polyps were discovered. An adenocarcinoma of the sigmoid colon was found in another patient six months prior to the diagnosis of a squamous cell carcinoma of the anal canal. Twenty-three patients had follow-up evaluation of the large bowel for metachronous lesions following treatment of the squamous cell carcinoma of the anal canal. Ten patients underwent colonoscopy, three patients had a barium enema, and ten autopsies were available for analysis. In this group metachronous lesions consisted of two adenomatous polyps and one hyperplastic polyp.

Adult↗
PubMed1987

Dental and bone abnormalities in patients with familial polyposis coli.

Dental and bone abnormalities of the maxilla and mandible are present in approximately 80% of patients with familial polyposis coli. The dental abnormalities include impacted teeth (other than third molars), supernumerary teeth, congenitally missing teeth, fused roots of first and second molars, and unusually long and tapered roots of posterior teeth. The bone lesions consist mostly of osteomas, either isolated or in clusters, in the maxilla and mandible or of exostoses with lateral and/or lingual extensions. Since dental and bone abnormalities are already present early in life there is a strong suggestion that they may be used as diagnostic features in the recognition of familial polyposis coli.

Adenomatous Polyposis Coli↗
PubMed1987

Follow-up colonoscopy in patients with colorectal adenomatous polyps.

Forty-four asymptomatic patients with adenomatous colorectal polyps were followed by repeated colonoscopies and subsequent removal of new polyps. The median follow-up time was 34 months (range, 4 to 131 months). Twenty-six patients (59 percent) developed new adenomatous polyps. The recurrence rate was 69 percent in patients with multiple polyps compared with 54 percent in patients with a single polyp. The location of new polyps was in the same colonic segment in 81 percent of the patients, but not at the same site in the colon where a previous polyp had been removed. The histopathology and size of new polyps compared with the initial polyps showed a significant improvement in histopathology toward more benign polyps (P less than 0.02) and smaller polyps (P less than 0.001). In patients who initially had single adenomatous polyps, new polyp(s) were diagnosed after a mean time of 23 months compared with 13.5 months in patients with two or more adenomatous polyps initially. Patients with atypia in initial polyp(s) developed new polyp(s) after a mean time of 11 months compared with 23 months in patients without atypia. The mean time from a colon with no polyps to the diagnosis of a new adenomatous polyp less than 5 mm in size was 11.5 months, which was a statistically significant shorter time than the 19.4 months observed for the development of polyps 5 mm or larger.

Adult↗
PubMed1987

The role of colonoscopy and flexible sigmoidoscopy in screening for colorectal carcinoma.

Six hundred thirty-two patients were referred to the Colorectal Clinic from February 1983 to February 1986 for screening with the Pentax 65 cm flexible sigmoidoscope. Forty-nine of these patients (8 percent) had adenomatous polyps. There were 27 males and 22 females. The mean distance examined by the 65 cm flexible sigmoidoscope was 55 cm. Five patients were excluded from analysis, leaving 44 patients who underwent colonoscopy to the cecum. At the time of colonoscopy, 15 of the 44 patients (34 percent) had one or more adenomatous polyps beyond reach of the 65 cm flexible sigmoidoscope. The remaining 29 patients who underwent colonoscopy had no polyps beyond reach of the 65 cm flexible sigmoidoscope. Thirty adenomatous polyps, one invasive carcinoma of the ascending colon, and one hyperplastic polyp were found in these 15 patients. In summary, 34 percent of patients found to have adenomatous polyps within reach of the 65 cm flexible sigmoidoscope harbored one or more adenomatous polyps in the proximal colon at the time of colonoscopy. A positive 65 cm flexible sigmoidoscope examination requires colonoscopy to identify and remove proximal premalignant lesions, thereby aborting the polyp-cancer sequence.

Colonic Neoplasms↗
PubMed1987

Sputum cytology for the detection of pulmonary metastases from colorectal carcinoma.

Twenty-two patients with pulmonary metastases from adenocarcinoma of the colon and rectum had sputum samples examined for cytology. All patients had lesions demonstrated on chest roentgenography and eight patients also underwent bronchoscopy. Three or more sputum samples were examined for eight patients, two samples for seven patients, and seven patients had one sample only examined. In five of 22 patients, the sputum samples were reported to be unsatisfactory for cytodiagnosis. Of the remaining 17, nine patients had at least one positive result for metastatic adenocarcinoma and in two additional cases the sample showed atypical cells. The result was therefore positive or atypical in 11 of 17 patients (65 percent). The positive cytology rate reported (79 percent for multiple pulmonary metastases) represents an improvement compared with previously published work. In this study 14 patients had either one or two samples collected for cytology and it is likely that the positivity rate would have been higher if three samples had been collected.

Adult↗
PubMed1987

A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma.

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.

Adenocarcinoma↗
PubMed1987

Biochemical and pharmacologic basis for potentiation of 5-fluorouracil action by leucovorin.

In vitro and in vivo studies have been carried out in mouse and human tumors to investigate the biochemical and pharmacologic basis for the selectivity of 5-fluorouracil (FUra) action. Combination chemotherapy with FUra and thymidine was performed to determine the therapeutic relevance of 5-fluorouridine triphosphate (FUTP) incorporation into RNA. The results of these studies indicate that modulation of FUra cytotoxicity by deoxythymidine (dThd) did occur but failed to produce any significant therapeutic advantages in patients with advanced colorectal cancer. Modulation of FUra bioactivation via the deoxyribonucleotide pathway by coadministration of high-dose folinic acid resulted in enhanced therapeutic response rate of gastrointestinal tumor patients. This manuscript summarizes the preclinical and clinical findings on the metabolic modulation of FUra activity by dThd and folinic acid.

Animals↗