Current therapy in the management of heterotopic ossification of the elbow: a review with case studies.

Heterotopic ossification, or the appearance of ectopic bone in para-articular soft tissues after surgery, immobilization, or trauma, complicates the surgical and physiatric management of injured joints. The chief symptoms of heterotopic ossification are joint and muscle pain and a compromised range of motion. Current therapies for prevention or treatment of heterotopic ossification include surgery, physical therapy, radiation therapy, and medical management. Unlike heterotopic ossification of the hip, heterotopic ossification of the elbow has not been extensively investigated, leaving its optimal management ill-defined. To remedy this deficiency, we review risk factors, clinical anatomy, physical findings, proposed mechanisms, and current practice for treatment and prevention of heterotopic ossification. We then consider and draw conclusions from four cases of elbow injury treated at our institutions (three complicated by heterotopic ossification) in which treatment included surgery, radiation therapy, physical therapy, and medical therapy. We summarize our institutional practices and conclude with a call for a randomized clinical trial to better define optimal management of heterotopic ossification of the elbow.

Current issues in techniques of prostate brachytherapy.

Adenocarcinoma of the prostate is the most common malignancy diagnosed among men in the United States today. Brachytherapy permits conformal radiotherapy and dose escalation, and it offers the convenience of a single-day outpatient procedure which is very attractive to patients with a busy life-style. The reported potency preservation rates with brachytherapy are superior to both external beam radiation therapy (EBRT) and surgery. The older retropubic techniques have been replaced by ultrasound or CT-guided transperineal techniques. Prostate brachytherapy may be temporary or permanent, and the planning techniques for either approach are similar. This review briefly discusses the advantages and limitations of each. Temporary techniques may be used with low dose rate or high dose rate applications. The basic steps include assessing prostate volume by any diagnostic modality (CT or ultrasonography), determining total activity needed to encompass the gland and deliver the appropriate minimum peripheral dose, and determining the pattern of placement of the seeds within the gland. Preplanning may be done either by ultrasound or by CT. The operative technique requires the visualization of the prostate in three dimensions and is performed using combination of ultrasound and fluoroscopy or fluoroscopy in two axes. The New York Hospital technique employs CT-based preplanning along with ultrasound and fluoroscopy during the operative procedure. Special circumstances that necessitate neoadjuvant hormonal therapy include interference from the pubic arch and large volume glands. An analysis of patients with stage T2a disease treated at the New York Hospital-Queens, from 1990-1995, reveals an actuarial clinical freedom from relapse of 79% at 5 years and a 5-year biochemical freedom from relapse of 64% which is comparable to that reported for similar risk groups of disease by other centers. Potency is preserved in greater than 80% of patients in our series. Patient selection criteria include the pre-treatment prostate-specific antigen (PSA) level, tumor grade (Gleason), stage of disease, and presence or absence of bilateral positive biopsies and/or perineural invasion. Based on our review of the literature and our clinical results, we have divided patients with prostate cancer into good, intermediate and poor risk groups. We recommend brachytherapy as the sole procedure for good risk patients, and a combination of external beam radiation therapy (EBRT) and brachytherapy for the intermediate risk group. Future avenues for research include a search for improved imaging techniques and possibly newer isotopes.

The pitfalls and complications of radiation therapy for esophageal carcinoma.

Radiation therapy is an important part of the management of esophageal cancer. Effective radiation therapy, however, requires careful evaluation of the tumor and the patient, cognizance of the tolerance of normal tissues in the area to the type of chemotherapy or surgical procedure employed, detailed planning, and streamlined delivery. When combining radiation therapy with other modalities of cancer treatment, physicians of both disciplines must be aware of the ability of one modality to potentiate the toxicity of the other. Therapy prescribed with the intention to cure and achieve long-term survival must be planned with consideration for the quality of life of the patient.

Management of peripheral vascular disease: innovative approaches using radiation therapy.

Despite the early successes at vascular recanalization with percutaneous transluminal angioplasty, vascular restenosis has emerged as a clinical problem of near epidemic proportions. Numerous pharmacologic and mechanical adjuncts have been tried with little success. Over the last few years, there have major advances in our understanding of the biology of the restenotic process. The process is now recognized as a proliferation disorder, and therapies akin to those used in the treatment of malignant diseases are being explored. Endovascular brachytherapy has shown strong potential in controlling this pathologic proliferative process in the laboratory and in early clinical studies. In this review we discuss some of the basic issues involved in vascular restenosis and the current status of endovascular brachytherapy.

The effect of ionizing radiation on signal transduction: antibodies to EGF receptor sensitize A431 cells to radiation.

What determines the degree of cell-resistance or sensitivity to ionizing radiation is not yet known. As a corollary to the ability of ceramide to induce apoptosis, some questions arise as to whether malignant cells escape apoptosis because of their inability to mount a ceramide response to inducers of apoptosis. To shed more light on the molecular mechanisms of tumor cell response to radiation, we tested whether exposure to ionizing radiation (of 200-1000 cGy) is associated with changes in ceramide levels in A431 tumor epithelial cells and whether the ability of ceramide to induce apoptosis is inhibited by protein kinase C (PKC) activation. Our studies demonstrate an immediate decrease in cellular levels of ceramide in response to radiation, while sphingosine levels increase. Under the same conditions the cellular 1,2-diacylglycerol (DAG) levels decrease as well, being accompanied by the translocation of PKC alpha from the membrane to the cytoplasm. Elevation of membrane PKC levels by 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment had no effect on cell survival after irradiation, while treatment with EGF during and after irradiation augmented cell survival. Moreover, monoclonal antibodies to the EGF receptor (EGFR) sensitize cells to radiation by facilitating radiation-induced apoptosis. It is thus plausible that in human Squamous carcinoma cells, radiation activates predominantly the EGFR to induce resistance, while both sphingomyelin and PKC signal transduction pathways are deactivated and demonstrate no significant role in the modulation of the sensitivity or the resistance of A431 cells to ionizing radiation.

A nomograph for permanent implants of palladium-103 seeds.

103Pd is being substituted for 125I in permanent implants for which it is desired to deliver a higher initial dose rate while maintaining readily achieved radiation protection. We have constructed a nomograph to assist in determining both the total seed strength required and the appropriate needle spacing for 103Pd implants. We have calculated the "matched peripheral dose" (MPD), that is, the dose for which the isodose contour volume is equal to the target volume, for 64 125I and 13 103Pd actual implants as if 103Pd had been used for all of them, employing a computer lookup table based on single-seed dose distribution measurements in solid water. The calculated data were used to obtain a least-squares fit to a linear relationship between the logarithm of the total seed strength for a given MPD and the logarithm of the average dimension, da (cm). We found that, for a nominal MPD of 11,500 cGy, total seed strength (in mCi) is given by 3.2 da2.56. A 103Pd nomograph has been constructed on the basis of this power function relationship. Our nomographic guide for planning 103Pd implants calls for total seed strength to increase significantly faster as a function of target volume average dimension than is the case for 125I. This nomograph will facilitate the application of 103Pd seeds in permanent implants.

Head and neck extranodal non-Hodgkin's lymphomas in Indian patients.

Though radiotherapy has traditionally been the treatment of the choice for the patients with localised extranodal lymphomas of the head and neck areas, its adequacy as the sole modality of treatment has come to be questioned. The disease is shown to relapse in other distant extranodal sites especially the gastrointestinal tract. The addition of systemic chemotherapy has been suggested. Fifty-five patients with localised head and neck extranodal lymphomas were treated at the Tata Memorial Hospital during the period 1976-1982, 35 with radiation therapy alone and 20 with combination therapy. The total survival at 5 years was 65% for patients treated with radiation alone and 85% for those treated with combination therapy. The 5 year disease-free survival dropped to 45% for the former group but was 74% for the latter group. This difference was statistically significant (p less than 0.01). We infer that localised extranodal lymphomas be regarded as a systemic disease and be treated by a multimodal approach.