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Biomedical subjects

M Deutsch

Publications and source records attributed to M Deutsch.

At least 19 recordsLinked to original sources

Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990.

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus.

Adenocarcinoma

[Percutaneous aspiration embolectomy of the popliteal artery].

Twenty-eight patients (17 women, 11 men, average age 67 years, range 40-85 years) with embolic occlusions of the popliteal arteries were treated by aspiration embolectomy. 6 patients were in clinical stage IIb and 22 in stage III. In 25 of the 28 patients the occlusion was treated successfully. Complications could be treated non-surgically at the same time. 2 of the patients died within the first week of cerebral emboli, 2 further patients suffered recurrent emboli in the treated extremity during the first month. 17 patients who were followed up for six months were free of recurrences.

Adult

Early diagnosis of proximal femoral deficiency.

A case of proximal femoral deficiency in a fetus, associated with ventriculomegaly and oligohydramnios is described. Vaginal ultrasonographic diagnosis was made in the 14th week of gestation in a 37-year-old asthmatic woman. Ultrasonic follow-up until termination of pregnancy in the 20th week of gestation was performed. The importance of early diagnosis and the possible roles of oligohydramnios and antiasthmatic medications are discussed.

Adult

Murine typhus: forgotten but not gone.

An occasional patient presents the classical symptoms of a disease that has become uncommon. Typhus is an example of such a disease, since it is now well contained through control of its rodent reservoir. It is readily treated with tetracycline or one of its long-acting analogues, doxycycline or minocycline. Because typhus is infrequently encountered, the physician may not initially include it in his differential diagnosis. Our case serves as a remainder that with the increasingly frequent movement of persons from one geographic area to another, the uncommon rickettsial infection, murine typhus, should continue to be in the differential of a febrile patient. Furthermore, our case underscores the importance of including typhus in the differential of typhoid fever.

Acute Disease

Differentiating malignant from benign ovarian tumors with transvaginal color flow imaging.

The impedance to blood flow was examined by transvaginal color flow imaging in 53 ovarian masses before exploratory laparotomy. Serum CA 125 levels were measured in all subjects. Thirty-six had benign ovarian tumors and 17 had malignant ovarian tumors confirmed by histopathologic examination. Intratumoral blood vessels, detected in 16 of the malignant tumors, consistently demonstrated low impedance to flow, with a pulsatility index (PI) always below 1. The PI of the intraovarian or intratumoral blood vessels was greater than 1 in 35 of the 36 benign tumors, although 11 had suspicious sonographic findings (P less than .01) and 14 had elevated CA 125 levels (P less than .001). The sensitivity and specificity of the preoperative PI in detecting malignant ovarian tumors were 94 and 97%, respectively. The sensitivity and specificity of preoperative suspicious sonographic findings in detecting malignant ovarian tumors were 94 and 69%, and those of elevated preoperative serum CA 125 levels were 82 and 61%, respectively. Our results suggest that transvaginal color flow imaging may be a useful clinical tool in the preoperative evaluation of ovarian masses.

Adult

Significance of ipsilateral breast tumour recurrence after lumpectomy.

Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy.

Breast Neoplasms

Time of death of CNS tumor-bearing rats can be reliably predicted by body weight-loss patterns.

A request by the Institutional Animal Care and Use Committee for an alternative to death as an end point in a cancer research project using a rat brain 9L tumor cell model led to a search for reliable criteria for predicting time of death in this type of experiment. These experiments evaluated the therapeutic effectiveness of radiation alone, continuous intracerebral infusions of 5-iodo-2-deoxyuridine (IUDR) alone, and a combination of both therapies. We found that a characteristic pattern of body weight changes occurs after injection of 9L tumor cells into the brain ventricles or parenchyma. The initial phase was characterized by a loss of body weight which appeared to be related to surgery and, in the irradiated groups, to the subsequent doses of radiation under anesthesia on days 4, 6, and 7. After this initial phase (phase 1), a second period of weight change (phase 2) which was characterized by an overall gain of body weight interrupted temporarily in 76 out of the 149 rats by reversible episodes of weight loss of 1 to 5 days duration. The length of this phase 2 weight gain period was significantly extended by XRT-IUDR treatment in the rats with intraparenchymal tumors. The third and final phase consisted of a period of irreversible weight loss which may be related to cachexia. The third phase was similar in duration for control, XRT, IUDR and XRT-IUDR groups of rats and had a mean length of 9.8 +/- 0.27 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Growth properties of cultured human endothelial cells on differently coated artificial heart materials.

The cultivation of autologous endothelial cells on the blood surface of artificial hearts might prevent their detrimental thromboembolic complications. To investigate the growth characteristics of endothelial cells on theoretically suitable biomaterials, we compared three polyurethanes (Pellethane, Biomer, Enka) and three silicone rubbers (Elastosil, 3145 RTV, Medical Adhesive). All synthetic surfaces were precoated with an extracellular matrix (group 1), fibronectin (group 2), or a glutaraldehyde-preserved cellular matrix (group 3). After the seeding of 2.5 x 10(4)/cm2 human endothelial cells into the various surfaces, primary adherence, growth kinetics, and maintenance of monolayer integrity were studied for 13 days. On the three polyurethanes all precoating procedures resulted in endothelial cell proliferation and the formation of persistent monolayers. In contrast, on silicone rubbers a persistent coverage with a confluent endothelium could be achieved only on the glutaraldehyde-preserved cellular matrix. When endothelial cell growth was quantitatively assessed on all precoating substrates, the glutaraldehyde-preserved cellular matrix proved to be far superior on each of the synthetics (p less than 0.001). These results demonstrate the theoretical feasibility of endothelialization of artificial hearts in vitro. Provided such an endothelium can withstand the mechanical forces within an artificial heart, in vitro endothelialization might contribute to a regained attractiveness of the elective long-term implantation of artificial hearts.

Biocompatible Materials

A new rat brain tumor model: glioma disseminated via the cerebral spinal fluid pathways.

A rat brain tumor model has been developed with the clinical and pathological features of dissemination via the cerebral spinal fluid (CSF) pathways. A precise number of 9L gliosarcoma cells (5 x 10(2) to 5 x 10(5)) is stereotactically injected into the CSF of the lateral ventricle. The interval until the onset of neurological symptoms and then death is reproducible and dependent upon the number of cells injected. The median survival of three groups of rats receiving 5 x 10(5) cells in three different experiments was 17, 18 and 19 days respectively. For three groups receiving 5 x 10(4) cells, the median survival was 23, 24 and 25.5 days respectively and for two groups receiving 5 x 10(3) cells the median survival was 28 and 30 days respectively. The animals developed multiple tumor implants along the CSF pathways usually resulting in hydrocephalus. This tumor model was developed to simulate dissemination via CSF pathways as seen with medulloblastoma and other primitive neuroectodermal tumors of the central nervous system. It will be used to evaluate the therapeutic efficacy of intraventricularly administered anti-neoplastic drugs against small implants and malignant cells in the CSF pathways.

Animals

Intra-cerebral ventricular infusion of 5-iodo-2-deoxyuridine (IUDR) as a radiosensitizer in the treatment of a rat glioma.

The efficacy of 5-iodo-2-deoxyuridine (IUDR) as a radiosensitizer when administered by continuous infusion into the cerebral spinal fluid (CSF) of the lateral cerebral ventricle was evaluated in a 9L gliosarcoma rat brain tumor model. Stereotactic implantation of a 5 x 10(4) tumor cell suspension into the left caudate nucleus was carried out in four groups of 10 rats each. Control animals had a median survival of 16.9 days (range 16-21 days). IUDR, 8.4 mg over 7 days administered by continuous infusion into the left lateral ventricle produced a slight survival advantage (median survival 21.5 days, range 12-56). Irradiation of the entire brain, 8 Gy on days 4, 6 and 7 after tumor cell implantation also produced a slight improvement in survival (median 19.5 days, range 17-34). The combination of radiation and IUDR infusion into the CSF produced a marked survival advantage (median 30.5, range 22-54) compared to the control and single modality treatment groups. This is the first demonstration of the effectiveness of IUDR as a radiosensitizer when administered into the lateral cerebral ventricle in the treatment of an intraparenchymal brain tumor.

Animals

Megavoltage external beam irradiation of craniopharyngiomas: analysis of tumor control and morbidity.

From 1971 to 1985, 21 patients received megavoltage external beam radiation therapy at the University of Pittsburgh for control of craniopharyngioma. Minimum tumor doses prescribed to the 95% isodose volume ranged between 51.3 to 70.0 Gy. Median total dose was 60.00 Gy and median dose per fraction was 1.83 Gy. Three deaths occurred from intercurrent disease and no deaths from tumor progression. Actuarial overall survival was 89% and 82% at 5 and 10 years. Actuarial local control was 95% at 5 and 10 years. Radiation related complications included one patient with optic neuropathy, one with brain necrosis, and one that developed optic neuropathy followed by brain necrosis. The high dose group of patients who received a NSD or Neuret equivalent of greater than 60 Gy at 1.8 Gy per fraction had a significantly greater risk of radiation complications (p = .024). The actuarial risk at 5 years for optic neuropathy was 30% and brain necrosis was 12.5% in the high dose group. Tumor control in the high dose group was not shown to be significantly better. Any possible benefit in tumor control in treating patients with craniopharyngioma with doses above 60 Gy at 1.8 Gy per fraction appears to be offset by the increased risk of radiation injury.

Adolescent

[Percutaneous atherectomy of the pelvic and leg arteries].

Percutaneous atherectomy, using a Simpson atherectomy catheter, was performed in 70 patients (43 men, 27 women) whose average age was 72 years (range 42 to 87 years). Between June 1988 and July 1989 all patients with disease in suitable localisations were treated in this way. The Doppler sonographic index before treatment was 0.6 (SD = 0.15), after treatment 0.89 (SD = 0.13). Recurrence was 21% after six months and 29% after twelve months. Atherectomy is superior to balloon dilation in the treatment of solitary eccentric stenoses of the superficial femoral artery and of the popliteal artery.

Adult

Verification of electron beam therapy with storage phosphor images: precision of field placement.

Portal verification images were generated from the photon contamination in electron beams produced by a linear accelerator during treatment of patients receiving high-energy electron radiation therapy (8-14 MeV). An experimental storage phosphor system was used to record the images and display them on laser-printed film. Images were obtained from four or more treatment fractions from 21 cases of head and neck cancer. Precision in field placement was estimated by determining the position of a selected anatomic landmark relative to the center of the field for each series of images. The average standard deviation in the field-position measurements was 3.8 mm. Several procedural problems were also detected and corrected after review of the verification images. The results indicate that the emphasis placed on monitoring and control of field-positioning error in high-energy electron treatments should be similar to the emphasis placed on this aspect of error in photon treatment.

Electrons