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Biomedical subjects

D B Fischer

Publications and source records attributed to D B Fischer.

At least 19 recordsLinked to original sources
PubMed2000

Interim results of a randomized trial of mitomycin C as an adjunct to radical radiotherapy in the treatment of locally advanced squamous-cell carcinoma of the cervix.

The purpose of this study was to determine the efficacy of mitomycin C as an adjunct to radiotherapy for the treatment of locally advanced cervix cancer. Patients with squamous-cell carcinoma of the cervix, stages IB2-IVA, were randomized to receive radiotherapy alone or radiotherapy with concomitant mitomycin C. An initial cohort of 160 patients, having a mean follow-up of 46 months, is analyzed. Intravenous mitomycin C, 15 mg/M(2), was given on the first and sixth week of radiotherapy. The 78 patients in the radiotherapy with mitomycin C group and 82 patients in the radiotherapy alone group have a comparable distribution by age and stage (mean age 47 years; stage IB 3%, IIA 11%, IIB 48%, IIIA 1%, IIIB 36%, IVA 3%). The four-year actuarial survival rates for radiotherapy with mitomycin C and radiotherapy alone were 72% and 56%, respectively (P = 0.13). The four-year actuarial disease-free survival rates for radiotherapy with mitomycin C and radiotherapy alone were 71% and 44%, respectively, a statistically significant difference (P = 0.01). The four-year actuarial local recurrence-free survival rates for patients receiving radiotherapy with mitomycin C and radiotherapy alone were 78% and 63%, respectively (P = 0.11). Differences in four-year distant recurrence-free survival between radiotherapy plus mitomycin C and radiotherapy alone were significantly different at 85% vs. 61% (P = 0.01); this analysis is not adjusted for local failure. On subgroup analysis, stage III-IVA patients had a four-year actuarial disease-free survival of 75% for radiotherapy plus mitomycin C compared with 35% for radiotherapy alone (P = 0.03). There were no treatment- related deaths. Mild hematologic toxicity was seen only in the group treated with mitomycin C. No excess in non-hematologic toxicity has been observed thus far with combined mitomycin C and radiotherapy. In this open phase III trial of mitomycin C as an adjunct to radical radiotherapy for squamous-cell carcinoma of the cervix, there were minimal hematologic effects and no increase in acute radiation reactions. A statistically significant difference in favor of patients receiving mitomycin C is shown for disease-free survival. Thus far, there are trends in favor of those patients receiving mitomycin C for survival and local control. Patients with more advanced stage disease, predominantly stage IIIB, appear to have the most benefit. These preliminary results support the hypothesis that targeting hypoxic cells may lead to a therapeutic enhancement in the radiotherapy of cervix cancer. This trial continues to accrue patients and follow-up data. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 206-223 (2000).

Actuarial Analysis↗
PubMed2000

Improving longevity of prosthetic dialysis grafts in patients with disadvantaged venous outflow.

OBJECTIVE: Angioaccess for hemodialysis in an extremity with disadvantaged venous outflow has reduced long-term patency. We hypothesized that arteriovenous bridge graft patency could be improved in patients with disadvantaged venous outflow by preoperative venous duplex mapping. METHODS: The charts of 114 patients who underwent 115 prosthetic arteriovenous bridge grafts were reviewed. Disadvantaged venous outflow was defined on the basis of any combination of prior arteriovenous bridge graft, multiple venipunctures, and clinical examination. Patients were grouped according to the presence or absence of disadvantaged venous outflow. Three groups were analyzed: those with normal venous outflow who had an initial arteriovenous bridge graft (NML), those with disadvantaged venous outflow who had only a clinical examination before redo arteriovenous bridge graft (REDO/DVO), and those with disadvantaged venous outflow who underwent preoperative duplex scanning venous evaluation (MAP/DVO). Life table primary and secondary 12-month patency rates were compared by means of log-rank analysis. RESULTS: Life table analysis yielded 6-month primary patency rates of 65.9% +/- 5.7%, 66.4% +/- 7.3%, and 43.8% +/- 10.9% for NML, MAP/DVO, and REDO/DVO, respectively. The secondary patency rates at 6 months for NML (91.9% +/- 3.4%) and MAP/DVO (91.1% +/- 4. 9%) were statistically equivalent, and both were significantly better than the patency for REDO/DVO (75.0% +/- 10.0%; P =.004 and P =.04, respectively). This trend persisted beyond 12 months. CONCLUSION: Preoperative evaluation of venous anatomy in patients with disadvantaged venous outflow results in an arteriovenous bridge graft patency comparable to that seen in patients undergoing initial arteriovenous bridge grafts. Vein mapping improves arteriovenous bridge graft durability in the patient with disadvantaged venous outflow by allowing the surgeon to select venous return that is in direct continuity with the central venous system.

Adult↗
PubMed2000

Second malignancies after treatment of early-stage breast cancer: lumpectomy and radiation therapy versus mastectomy.

PURPOSE: To determine the risk of second malignancies after lumpectomy and radiation therapy (LRT), and to compare it with that in a similar cohort of early-stage breast cancer patients undergoing mastectomy without radiation (MAST). PATIENTS AND METHODS: Between January 1970 and December 1990, 1,029 breast cancer patients at our institution underwent LRT. A cohort of 1,387 breast cancer patients who underwent surgical treatment by mastectomy (MAST), and who did not receive postoperative radiation during the same time period, served as a comparison group. Second malignancies were categorized as contralateral breast versus nonbreast. In the cohort of patients undergoing LRT, a detailed analysis was carried out with respect to age, disease stage, smoking history, radiation therapy technique, dose, the use of chemotherapy or hormone therapy, and other clinical and/or pathologic characteristics. RESULTS: As of March 1999, the median follow-up was 14.6 years for the LRT group and 16 years for the MAST group. The 15-year risk of any second malignancy was nearly identical for both cohorts (17.5% v 19%, respectively). The second breast malignancy rate at 15 years was 10% for both the MAST and LRT groups. The 15-year risk of a second nonbreast malignancy was 11% for the LRT and 10% for the MAST group. In the subset of patients 45 years of age or younger at the time of treatment, the second breast and nonbreast malignancy rates at 15 years were 10% and 5% for patients undergoing LRT versus 7% and 4% for patients undergoing mastectomy (P, not statistically significant). In the detailed analysis of LRT patients, second lung malignancies were associated with a history of tobacco use. There were fewer contralateral breast tumors in patients undergoing adjuvant hormone therapy, although this did not reach statistical significance. The adjuvant use of chemotherapy did not significantly affect the risk of second malignancies. CONCLUSION: There seems to be no increased risk of second malignancies in patients undergoing LRT using modern techniques, compared with MAST. Continued monitoring of these patient cohorts will be required in order to document that these findings are maintained with even longer follow-up periods. With nearly 15 years median follow-up periods, however, these data should be reassuring to women who are considering LRT as a treatment option.

Adult↗
PubMed1994

Preoperative serum prostate-specific antigen and Gleason grade as predictors of pathologic stage in clinically organ confined prostate cancer: implications for the choice of primary treatment.

PURPOSE: Despite careful preoperative staging, approximately 50% of patients who undergo radical prostatectomy for clinical stage A2 (T1b-c) and B (T2) prostate cancer are found to have pathologic stage C (T3-4) or D (N1) disease. This study investigates whether preoperative serum prostate specific antigen (PSA) and Gleason grade predict pathologic stage among patients with clinically organ confined prostate cancer. METHODS: The records of all 63 patients who underwent attempted pelvic lymphadenectomy and radical prostatectomy for adenocarcinoma of the prostate at our institution in 1990-91 were retrospectively reviewed. RESULTS: Patients with a preoperative serum PSA of 12.5 ng/mL or greater had an 81% incidence of pathologic upstaging to stage C (T3-4) or D (N1) compared with 38% for patients with a PSA less than 12.5 (p = 0.0015). The incidence of various pathologic findings for prostate specific antigen > or = 12.5 vs. prostate specific antigen < 12.5 was as follows: seminal vesicle involvement 29% vs. 5% (p = 0.0186), lymph node metastases 24% vs. 0% (p = 0.0029), capsular penetration 71% vs. 38% (p = 0.0424), and positive margins 47% vs. 36% (p = 0.56). None (0/3) of the patients with Gleason grade 4 or less were pathologically upstaged compared with 49% (24/49) of patients with grade 5-7 tumors (p = 0.15) and 82% (9/11) of patients with grade 8 or higher cancers (p = 0.0474, grade 5-7 vs. 8-10). Within the group of patients with Gleason grade 5-7, a prostate specific antigen of 12.5 ng/mL or greater predicted an 79% rate of upstaging compared with 37% for patients with prostate specific antigen less than 12.5 (p = 0.0098). CONCLUSION: Patients with clinical Stage A2 (T1b-c) or B (T2) prostate cancer who have Gleason grade 8-10 tumors and those patients with Gleason grade 5-7 tumors with a preoperative serum prostate specific antigen of 12.5 ng/mL or higher have a high incidence of pathologic upstaging. These patients should be preferentially treated with external beam radiation in most cases.

Adenocarcinoma↗
PubMed1993

Local recurrence versus new primary: clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting.

PURPOSE: The purpose of this study was to perform a detailed clinical pathological analysis of breast relapses in patients treated with conservative surgery and radiation therapy in an effort to classify those relapses as true local recurrences or second primary tumors, and to assess the prognostic and therapeutic implications of such a classification system. METHODS AND MATERIALS: Of 990 patients treated with conservative surgery and radiation therapy at our facilities prior to December 1987, 82 patients have experienced a relapse in the conservatively treated breast as the primary site of failure. Patients were classified as having new primary tumors if they fulfilled any one of the following criteria: a) breast relapse occurring at a site distinctly removed from the original tumor; b) histology of the breast relapse compared with the original tumor consistent with a new primary; or c) DNA flow cytometry converting from an aneuploid primary to a diploid relapse. RESULTS: As of 2/92, with a median follow-up of 5.4 years from the time of breast relapse, the overall 5-year survival rate following breast relapse was 55%. Forty-seven patients were classified as true recurrences and 33 patients were classified as new primaries. Patients classified as true recurrences had a shorter median time to breast relapse than patients classified as new primaries (3.16 years vs. 5.42 years, p < .05) and an inferior post breast recurrence survival rate compared to patients classified as new primaries (36% vs. 89%, p < .05). Residual disease outside of the recurrent tumor bed was also noted to be more frequent in patients classified as true recurrences compared to patients classified as new primaries (48% vs. 16%, p < .05). CONCLUSION: Based on the clinical and pathological criteria outlined, it appears that a significant portion of patients experiencing a relapse in the conservatively treated breast may have new primary tumors as opposed to true local relapses. Distinction between a true recurrence and a new primary tumor may have significant prognostic implications. Uncertainties associated with the clinical and pathological criteria are presented and further investigations with genetic fingerprinting techniques to establish the clonality of breast relapses are presented and discussed.

Adult↗
PubMed1993

Arachidonate and renal function.

Basic and clinical investigations into the roles of arachidonate-derived compounds in regulating renal function under normal and pathophysiological conditions continued to expand over the past year. Exciting new insights regarding the pathobiology of thromboxane A2 revealed new roles for this potent cyclooxygenase-derived vasoconstrictor in the glomerular dysfunction that accompanies inflammatory disorders and insulin-dependent diabetes. Major advances have extended our understanding of the proinflammatory actions of leukotriene B4 and other 5-lipoxygenase compounds in mediating glomerular injury during experimental glomerulonephritis. Intriguingly, emerging evidence suggests the presence of an anti-inflammatory arm in the lipoxygenase pathway, ie, 15-lipoxygenase, products of which may act as endogenous leukotriene antagonists. New information has also become available about the renal biology of cytochrome P-450 metabolites of arachidonic acid as well as about nonenzymatically generated biologically potent eicosanoids, the F2-isoprostanes.

Animals↗
PubMed1992

Fifteen-S-hydroxyeicosatetraenoic acid (15-S-HETE) specifically antagonizes the chemotactic action and glomerular synthesis of leukotriene B4 in the rat.

In models of experimental glomerulonephritis, there is temporal concordance between the shift in the glomerular cellular infiltrate from neutrophils (PMN) to macrophages/monocytes and the suppression of glomerular leukotriene B4 (LTB4) generation. Since macrophages are a rich source of 15-lipoxygenase (15-LO) products, we investigated whether the principal product of arachidonate 15-lipoxygenation, 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), was capable of antagonizing the proinflammatory actions of LTB4 in the rat. PMN exhibited chemotaxis to LTB4 in a dose dependent manner with an LC50 of 10(-8) M. When rat neutrophils were pre-treated with 15-S-HETE, chemotaxis to LTB4 was inhibited in a dose dependent manner (maximal at 30 microM 15-S-HETE) but, the same concentration did not inhibit chemotaxis to n-formyl-1-methionyl-1-phenylalanine (FMP). 12-S-HETE (30 microM) did not inhibit chemotaxis to LTB4. Glomeruli from rats injected with nephrotoxic serum three hours earlier generated increased levels of LTB4; prior exposure of such glomeruli to 15-S-HETE totally normalized LTB4 production. The glomerular production of 15-S-HETE and LTB4 was also determined 3 hours, 72 hours and 2 weeks after administration of nephrotoxic serum. Whereas there was an early, short-lived, burst of LTB4 followed by a return to baseline levels, the production of 15-S-HETE increased steadily over the two week period and was present in amounts fivefold greater than LTB4. Thus, these studies assign a role for locally generated 15-LO derivatives in arresting LTB4-promoted PMN infiltration and suppressing LTB4 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Breast conservation therapy in patients with mammographically undetected breast cancer.

The authors reviewed their experience with 542 patients with breast cancer who were treated with conservative surgery and radiation therapy (CSRT) and analyzed the outcome in those patients whose tumors could not be detected with mammography. Fifty-five of the patients (10.1%) had a palpable, pathologically confirmed breast carcinoma and a negative preoperative mammogram. Routine follow-up included annual mammography and physical examination. The local recurrence, 5-year actuarial survival, and 5-year disease-free survival rates for these 55 patients did not differ significantly from those for patients with positive mammograms. There were six cases of local breast recurrence in this subgroup. Four of five cases were visible on mammograms (one patient did not undergo mammography at the time of recurrence); two of the cases were detected with mammography alone following physical examination with negative results. The authors conclude that patients with palpable but mammographically occult early-stage breast cancer are suitable candidates for CSRT and that mammography is a mandatory part of follow-up of conservatively treated patients.

Actuarial Analysis↗
PubMed1989

Randomized clinical trial of mitomycin C as an adjunct to radiotherapy in head and neck cancer.

A randomized prospective clinical trial was carried out to assess the usefulness of the addition of mitomycin C to radiation therapy used alone or in combination with surgery for the treatment of squamous cell carcinoma of the head and neck region. One hundred and twenty patients with biopsy proven tumor of the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx were randomly assigned to receive or not receive mitomycin C; all other aspects were similar in the two treatment groups. One hundred and seventeen patients were evaluable with a median follow-up time of greater than 5 years. Acute and chronic normal tissue radiation reactions were equivalent in the two treatment groups. Hematologic and pulmonary toxicity were observed in the drug treated patients. Actuarial disease-free survival at 5 years was 49% in the radiation therapy group and 75% in the radiation therapy plus mitomycin C group, p less than 0.07. Local recurrence-free survival was 66% in the radiation therapy group and 87% in the radiation therapy plus mitomycin C group, p less than 0.02. The findings demonstrate that mitomycin C can be administered safely as an adjunct to radiation therapy in the treatment of head and neck cancer. The drug improves local tumor control without enhancing normal tissue radiation reactions.

Adult↗
PubMed1988

Radiation therapy for squamous cell carcinoma of the esophagus.

Between 1965 and 1981, 119 patients with squamous cell carcinoma of the esophagus were treated with radiation therapy with curative intent. Radiation was employed in combination with surgery and delivered pre- and/or postoperatively in 20 patients (17%). The remainder received radiotherapy alone. The overall survival rate was statistically higher in patients who had surgery and radiation compared to the group receiving radiation alone. The one-, two-, and five-year survival rates of patients receiving combined treatment vs radiotherapy alone were 65% vs 35%, 25% vs 14%, and 15% vs 6%. Age, total radiation dose, and inclusion of the supraclavicular areas in the radiation portals did not impact on outcome. Other prognostic factors are discussed. Long term survivors were noted to be at substantial risk for the development of a second epidermoid malignancy in the upper aerodigestive tract. Cumulative risk at five years was approximately 25%.

Adult↗
PubMed1988

Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer.

From 1970 to 1983, 1,646 lung cancer patients were referred for treatment to the Hunter Radiation Therapy Center, Yale-New Haven Hospital. Forty-three patients had clinical Stage I non-small cell lung cancer felt to be surgically resectable but were treated with radical radiation therapy either for medical reasons (37 patients) or because the patient refused surgery (six patients). This group of clinical Stage I lung cancer patients is understaged by modern criteria since the majority of patients did not have thoracic CT scans and staging was based on fairly limited clinical and radiographic studies. The histological diagnosis was squamous cell carcinoma in 53% of the Stage I patients, adenocarcinoma in 25%, and other non-small cell histologies in 22%. All patients were treated with megavoltage irradiation and the mediastinum was treated in 88% of the patients. Eleven patients were treated with a continuous course (CC) and 32 patients received split course (SC) therapy based on physician preference. The CC consisted of a median fraction size of 200 cGy to a total median dose of 5900 cGy in 6-7 weeks. The SC used a median fraction site of 275 cGy to a total median dose of 5400 cGy over a 6-week period with a 2-week rest in the middle of treatment. The actuarial survival rate of the 43 clinical Stage I patients was 36% at 3 years and 21% at 5 years. Intrathoracic failures occurred in 39% of the patients. Despite the fact that the CC group was similar to the SC group in terms of age, histology, and tumor extent, the CC patients had a lower thoracic failure rate (2/11) versus 15/32), a longer median survival (51.6 months versus 27 months), and a better actuarial 5-year survival rate (45% versus 12%) when compared to the SC patients. Using Cox regression analysis to compare survival curves, the CC group had a significantly better survival compared to the SC group (p = .04).

Adenocarcinoma↗
PubMed1986

A clinical and histopathologic analysis of the results of conservation surgery and radiation therapy in stage I and II breast carcinoma.

One hundred eighty women with clinical Stage I or II operable breast carcinoma were treated by radiotherapy following local tumor excision at Yale-New Haven Hospital through 1980. With a median follow-up time of 6.9 years, the actuarial 5-year overall and disease-free survival rates were 82% and 78%, respectively. The 5-year actuarial breast-recurrence-free survival rate was 92%. Several clinical-histopathologic features and treatment parameters were assessed for their significance as predictors of local breast failure or distant relapse. Cox lifetable regression analysis showed that patients with clinical Stage II carcinomas had significantly worse overall and relapse-free survival rates, but clinical stage alone had no effect on the rate of breast recurrence. Furthermore, a decrease in overall and disease-free survival was evident when necrosis was present in the tumor or when patients had an infiltrating lobular carcinoma. Breast recurrence-free survival was also influenced adversely by the presence of these two tumor features, especially when either tumor necrosis or infiltrating lobular carcinoma was found in conjunction with clinical Stage II lesions. Other histologic features such as grade, vascular invasion, perineural invasion, or the presence of an intraductal component of carcinoma did not affect outcome, nor did the treatment techniques employed appear to have a differential effect.

Actuarial Analysis↗
PubMed1985

A population-based study of survival after scrotal carcinoma.

In previous reports on scrotal carcinomas, overall 5-year survival rates have varied from 18% to 70% without explanation. In this study, survival was determined through the active follow-up of the Connecticut Tumor Registry for 65 cases of scrotal carcinoma diagnosed in the state from 1935 to 1980. The overall actuarial probability of surviving 5 years was 0.57. Stage and age at diagnosis were statistically significant predictors of survival (P less than 0.001 and P = 0.016, respectively). Survival varied progressively with combinations of these two variables with subjects younger than age 65 years and localized at diagnosis having 5-year survival of 0.75, compared to 0.17 for subjects age 65 years and older with regional or distant spread; these survival outcomes encompassed those of previous reports. With the passage of more than four decades, no improvement in survival was detectable. Initial radiotherapy, given to nine cases, also bore no detectable relationship to survival after adjustment for other variables. The 30 men in metalworking occupations previously shown to be associated with this cancer were not more frequently diagnosed with the cancer in localized stage, and showed a survival similar to that for the 29 men in other occupations.

Actuarial Analysis↗
PubMed1984

Differential effect of cycloheximide on normal tissue tolerance and tumor control in irradiated rats.

The effect of the protein synthesis inhibitor cycloheximide (CHM) on normal tissue tolerance and tumor control in the rat following single doses of radiation has been studied. We have previously shown that the drug protects against skin damage when administered prior to irradiation of the hind limbs. It does not protect against six-month lethality when given prior to irradiation of the kidneys. In the present studies protection of rat bone marrow as evidenced by 30-day lethality was observed when CHM was given prior to whole-body irradiation. When CHM was given to rats bearing the BA1112 tumor, it had no protective effect on radiocurability. Therapeutically favorable differential protection of rapidly proliferating normal tissue over tumor can be achieved when CHM is administered prior to single radiation doses in the rat. This effect is most likely due to inhibition of protein synthesis and resultant interruption of the cell cycle in proliferating normal tissue. Further studies are required to determine the clinical applicability of CHM.

Animals↗
PubMed1983

The effect of subtotal resection on the dose of radiation required to cure the rat rhabdomyosarcoma BA1112.

Dose response curves were established for local control of the rat rhabdomyosarcoma BA1112 for radiation alone and for radiation following a cytoreductive operation. Removal of one-half of the tumor prior to irradiation did not significantly alter the dose of radiation necessary to cure 50 per cent of the tumors. This experimental result confirms the theoretic predictions and suggests that, to be useful in combination with radiation, surgical treatment must remove in excess of 90 per cent of the tumor.

Animals↗
PubMed1983

Differences in breast cancer risk factors according to the estrogen receptor level of the tumor.

One hundred and forty-eight postmenopausal breast cancer cases and 585 postmenopausal controls were included in an investigation of whether various risk factors for breast cancer are associated with the level of estrogen (E) receptor (ER) protein in the tumor. In an intracase analysis, the tumor ER level was positively associated with nulliparity, late age at first live birth, a history of benign breast disease, and having breast-fed at least 1 child and was negatively associated with previous use of E replacement therapy. A case-control analysis suggested that the first three variables, established risk factors for breast cancer, are associated with an increased risk for malignant breast tumors that are ER-positive but not for those that are ER-negative. This analysis did not provide a clear interpretation of the findings in the intracase comparisons with regard to prior breast-feeding and the use of E replacement therapy.

Aged↗