Biomedical subjects
Publications and source records attributed to S Kramer.
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One hundred and ten patients were seen in the Department of Radiation Therapy at Thomas Jefferson University Hospital for pancreatic tumours between January 1975 and June 1980. Twelve patients had previously been treated for a non-pancreatic malignancy. Pancreatic biopsies were performed in nine patients and were interpreted as pancreatic carcinoma. When the previous pathological material was compared to the pancreatic biopsy, the diagnosis was changed in five of the 12 patients to recurrent non-pancreatic malignancy. We emphasise the importance of the distinction between primary pancreatic malignancy and metastatic disease in the pancreas.
One-hundred-twelve children with primary brain tumors received definitive radiotherapy between the years 1958--1979. Sixty-nine patients were alive at intervals of 1--21 years. Thirty-eight patients underwent neurologic and endocrine evaluation, psychologic and intelligence testing, and assessement for second malignancy post-treatment. A second intracranial malignancy developed in one child, for an incidence of 1.6%. Performance status was good to excellent in 89% of the patients studied. Seventeen percent of the group were mentally retarded. Behavioral disorders were identified in 39% of the patients, 59% of the mothers, and 43% of the fathers. Of the 23 patients with nonparasellar tumors, six were found to have growth hormone deficiency, including two patients with panhypopituitarism. Disability was related to age under 3 years at the time of treatment and tumor extension to the hypothalamus.
This is a comparison of the rate of surgical complications in a group of patients with advanced but operable carcinoma of the head and neck who underwent surgery after preoperative radiotherapy (5000 rad in five weeks, 200 rad fractions, directed to the primary tumor area and neck) versus another group operated without prior irradiation. Both groups of patients formed part of a randomized prospective multiinstitutional trial of the Radiation Therapy Oncology Group (73-03). Of 229 patients who had planned operations, 88 (38%) developed some degree of surgical complications, and in 28 (12%) the complications were rated as severe. The most frequently reported complications were delayed healing and fistula formation each occurring in approximately one-fourth of each of the two treatment groups. Carotid blow-out occurred in 5% or less of the cases. No significant statistical difference between treatment groups was noted for the overall complication rate or specific type of surgical complications. A trend was noted towards more complications in the preoperative group for patients with lesions in the oropharynx and supraglottic larynx. However, an opposite trend towards more complications in the no prior irradiation group was observed among patients with lesions in the oral cavity and hypopharynx. Surgical mortality and postoperative hospital stay were not significantly different between treatment groups. We conclude that preoperative irradiation for carcinoma of the head and neck, with the stated dose, followed by surgery in 4-6 weeks, does not substantially increase the rate of overall or specific type of surgical complications, surgical mortality or hospital stay versus those patients operated without prior irradiation.
Folates may play a role in epileptic phenomena and may also be involved in synaptic events. Recently methyltetrahydrofolate was found to be a potent competitor for 3H-kainic acid binding sites in the cerebellum. The effects of 1 mM methyltetrahydrofolate (MTHF), 1 mM formyl-tetra-hydrofolate (FTHP) and 1 mM Na-folate (Na-F) were tested on the reflex activity of the isolated hemisected frog spinal cord. MTHF and FTHP were found to have an initial excitatory effect on the evoked ventral root responses. This was followed by a gradual decrease in the amplitudes of the ventral root responses. Sodium folate had only an inhibitory effect on these responses. When the evoked ventral root responses were totally inhibited by the folates the preparations did not respond to any of the following substances: (a) Kainic acid (KA), (b) L-glutamic acid (LG), (c) picrotoxin or (d) strychnine. All the folates had an inhibitory effect on the dorsal root responses. In most preparations neuronal activity was only partially restored by perfusion with normal Ringer solution. When the isolated spinal cords were bathed in either 0,5 mM KA or 1 mM LG similar results were obtained to that found with MTHF and FTHF. Glutamic acid diethyl ester (GDEE, 1 mM), however, yielded similar results to that seen with Na-F. It seems that the glutamates and related substances differ in their ability as neuroexcitants, but all share the common ability to inhibit synaptic activity when nervous tissue is exposed to the substances for long periods. Some of the folates share with KA some degree of neurotoxicity. These experiments could also not point out a separate kainic receptor in the frog spinal cord.
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Since 1976, a new approach to adjuvant radiation therapy in carcinoma of the rectum has been used at Thomas Jefferson University Hospital. Seventy-eight patients with biopsy-proven invasive carcinoma of the rectum have been treated with low dose preoperative radiation, 500 rad given either on the day of or the day before surgery. Following surgery, the lesions were pathologically staged according to Astler-Coller's Modification of Duke's staging. Patients with good prognostic features (Stage A or B1) were followed with no further treatment while patients with poor prognostic characteristics (Stage B2, C1 and C2) were treated with aggressive postoperative pelvic radiation, 4500 rad delivered in five weeks. All patients entered into this study received the preoperative dose of 500 rad. Fifty-six patients underwent an A-P resection, four patients underwent a low anterior resection and ten patients had a combined abdominal transsacral resection. Eight patients were found to have liver metastasis at laparotomy and underwent a colostomy followed by palliative therapy. Twenty-nine patients were found to have early disease, Stage A or B1, and were given no further therapy. Of 41 patients with Stage B2 or C, 25 patients received the full course of postoperative radiation. Sixteen patients did not receive postoperative radiation for a variety of reasons. Follow-up in these patients ranges from six months to a maximum of 48 months with a median follow-up of 18 months. Sixty-nine of the total group of 78 patients are currently alive. Two patients with early tumor (Stage A or B1) have died of metastasis. One other patient with Stage A carcinoma died of unrelated causes. Two of the 25 patients receiving postoperative radiation developed metastatic disease, but none of the patients developed local recurrence in the pelvis. Six of 16 patients who should have received postoperative radiation, but did not recurred. Four of these six recurrences have been in the pelvis. Both the incidence of failure and the pattern of recurrence between these two groups of patients who did not receive postoperative radiation is suggestive of a better effect in the PR unrelated group. Survival of patients treated with this approach appears to be improved.
A study was conducted to provide baseline data on patterns of cerebrovascular disease incidence in the community of Washington County, Maryland, over two time intervals--1969-1971 and 1974-1976--and to evaluate any temporal trends with regard to their possible relation to reported declines in stroke death rates. Among the statistically significant changes in incidence between 1969-1971 and 1974-1976 were a decline in the rate of cerebral thrombosis and a concomitant increase in frequency of cerebrovascular disease-unspecified, most likely a reflection of a change in diagnostic terminology. In addition, the findings of a significant decrease in incidence of cerebral hemorrhage (for all ages over 55 years and both sexes) and a non-significant decrease in incidence rates for all types combined among those in the oldest age category between the two study periods support the role of changing incidence rates in the stroke death rate decline. It is clear, however, that monitoring of this community over a longer period of time will be necessary before the validity of these trends can be established and their causes elucidated. The need for more complete recording of historical data and clinical findings on admission, as well as adherence to standardized diagnostic and classification protocols was underscored by this study.
This paper reports the results of the PCS Outcome Surveys for radiation therapy treatment in six disease sites: cervix, Hodgkin's disease, seminoma of the testis, anterior two-thirds of tongue and floor of mouth, larynx and prostate. The survey reflects data obtained for patients treated in 1973. Results for early stages of disease are generally favorable in cancer of the cervix, prostate, testis, larynx and Hodgkin's disease. Control of disease in anterior two-thirds of tongue and floor of mouth was less favorable, but data suggest that more aggressive radiation therapy may contribute to better outcome for this site.
One hundred-twelve females with stage I-III breast carcinoma were treated primarily with radical megavoltage irradiation. The loco-regional area received 50 Gy/5 weeks with a boost to the primary site of 10 Gy/1 week to 20 Gy/2 weeks. Local control rates were as follows: 94 per cent in stage I, 86 per cent in stage II and 69 per cent in stage III. Survival rates were comparable to those reported by other authors. Complications correlated with disease stage and extent of radiation fields.
From 1975 through 1979, 25 patients with osteosarcoma received therapy with vincristine, high-dose methotrexate, citrovorum factor, and Adriamycin. Five patients had metastases prior to receiving chemotherapy, and 11 of the remaining 20 nonmetastatic patients received preoperative or preirradiation chemotherapy. Chemotherapy caused objective tumor regression in 1 of 5 patients with metastases and 1 of 11 with measurable primaries. All five patients with metastatic disease died 7-16 months from diagnosis. Of the 20 nonmetastatic patients, 4 did not have primary amputations: all died. Of 16 patients with primary amputations, 6 are alive relapse-free 24-86 months from diagnosis, and 10 are dead. The actuarial survival of 36% is not statistically different from that of historical control groups or from that of concurrent control groups treated with surgery alone. However, because most adjuvant chemotherapy studies have involved few patients, 36% survival is not statistically different from the 50-70+% survival reported in previous studies. Our data fail to demonstrate that the adjuvant chemotherapy has improved the survival rate of children with osteosarcoma. We support a randomized, controlled comparison of adjuvant chemotherapy and aggressive surgical resection.
In a statistically valid random sample of 387 patients selected from the national practice and treated with radiation therapy in 1973 for Hodgkin's disease, the 4-year recurrence-free survival was: stage IA, 82%; stage IIA, 75%; stage IIIA. 60%; and combined stages IB-IIIB, 50%. Observations of in-field recurrence in 996 separate lymph node areas show no dose-response relationship between 3000 and 5000 rad. The use of chemotherapy in stage IIIA Hodgkin's disease in the national practice is associated with a significant improvement in recurrence-free survival (P = 0.01). A group of 51 patients with stages IA-IIIA Hodgkin's disease, aged 5-15, treated with radiation therapy alone, has a 92% recurrence-free rate at 3 years with no major complications.
Eleven patients were entered in a phase I/II study to evaluate the toxicity and effectiveness of the use of misonidazole with radiation in cancer of the bladder. The radiation fractionization used is shown in Figure 1. Misonidazole was administered in a dose of 1.5 g/m2, 4-6 hours before the radiation dose. The large radiation dose (400 rad) used with misonidazole was designed to obtain maximum enhancement of radiation sensitizer effect. Only minor misonidazole toxicity was observed. Tumor regression was dramatic, with 7/9 patients achieving complete regression of disease. Three patients however, developed severe small bowel complications, probably from the unconventional radiation fractionation used. In view of this high complication rate, this study was terminated.
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A case of acute intermittent porphyria is presented. This case emphasizes the clinical, biochemical and endocrinological changes, and their possible aetiology is discussed. Treatment, especially the use of intravenous haematin, is also described.
Five whole-brain irradiation schedules ranging from 2000 rad in one week to 4000 rad in four weeks were evaluated in 1830 patients with cerebral metastases treated in two randomized studies by the Radiation Therapy Oncology Group. The duration of palliative effectiveness among those patients with favorable survival prognosis was investigated. Favorable subgroups were identified consisting of 123 ambulatory breast cancer patients with no soft tissue metastases, 373 ambulatory lung cancer patients with primary absent or no extracerebral metastases, and 65 ambulatory patients with other primaries and no extracerebral metastases. This group of 561 patients had a median survival of 28 weeks compared with 11 weeks for the remaining patients. Analyses of neurologic function control rates failed to show a significant benefit of higher doses. No advantage was demonstrated for treating brain metastases patients with favorable prognoses with more than one week of whole-brain irradiation.
The PCS Process Survey analyzed radiation therapy facilities to evaluate procedures in work-up and treatment of patients with cancer of the larynx, tongue, and nasopharynx. Types of facilities are compared to establish bench marks in performance of work-up and treatment procedures that can be used as a foundation for upgrading care and for adjusting studies to follow this paper. A statistical method is demonstrated that provides a "signature" of relative performance over a standardized set of procedural criteria. Facilities with resident training programs perform nearly all of these procedures much more consistently than do nontraining facilities. Facilities with full-time head therapists perform most procedures more consistently than do facilities with part-time heads. A third comparison of large versus small facilities shows that among training facilities size has no effect and that among full-time facilities size has a slight effect. Among part-time facilities, however, smaller ones fail to perform most procedures more often than larger facilities. The size difference is confounded with the full-time/part-time difference because part-time facilities are on the average smaller than facilities with full-time head therapists.
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