High-dose rate intracavitary radiation therapy for advanced head and neck tumors

Fifty-seven treatments were performed on 27 head and neck pateints with recurrent or residual tumors on a high dose rate, remote controlled afterloading unit: There were 16 cases of maxillary sinus tumors, 6 epipharynx, 3 alveolar ridge, 1 hard palate and 1 floor of mouth. All patients have been followed up more than 2 years except one. Five patients are alive without local recurrence for more than 2 years. In 13 patients local tumors disappeared once and normal mucosa covered the tumor sites. Two patients died from local bleeding. In six patients this method failed to destroy tumors. Our prupose was palliative local control: therefore, in two-thirds of cases treated we were successful with this easy method of nonfractionated acute intracavitary radiation. This result is favorable, considering that all cases treated here were failures following full dose external radiation, although the treatment had to be repeated more than twice in 15 cases. Relief of symptoms is excellent when this therapy is used.     

A convenient method for guarding against localized mucositis during radiation therapy

Metal restorations, such as full gold crowns and dental implants, can cause forward and back scatter radiation during radiation therapy with a dose enhancement to adjacent tissues. Mucositis, one of the most common complications of the radiation treatment of oral, as well as other head and neck malignancies can result. A method for constructing a buccolingual guard in the clinical setting using hydroplastic material is described. The guard can be easily oriented and adapted to an existing radiation stent, adding positional stability and patient comfort. When adequate thickness of material is used, the guard can attenuate forward and back scatter radiation, separate the adjacent tissues from metal restorations, and protect the oral mucosa from localized incidents of mucositis.     

High-dose rate iridium192 afterloading therapy in combination with external beam irradiation for localized prostate cancer

The number of donors aged 60 years and over has increased. This study examined discard rates and transplant outcomes in organs recovered from older donors. Data were obtained using a standard tool for donors aged 60 years and older during 1993 and 1994 and included demographics, medical history, use of vasopressors, renal/liver function studies, organ disposition, biopsy findings, and recipient organ function. Of 58 kidneys recovered, 24 were transplanted, 26 were used for research, and 8 were discarded. Of 14 livers recovered, 11 were transplanted, 1 was used for research, and 2 were discarded. Sixty-three percent of kidney recipients had immediate function; 79% at 30 days. Nine liver recipients had immediate function; 6 at 30 days, with 1 graft lost. Results show that kidneys and livers can be transplanted from older donors with positive outcomes. Factors such as medical history, use of vasopressors, and organ function studies may help predict organ disposition and function.     

Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer

CONTEXT: Interstitial radiation (implant) therapy is used to treat clinically localized adenocarcinoma of the prostate, but how it compares with other treatments is not known. OBJECTIVE: To estimate control of prostate-specific antigen (PSA) after radical prostatectomy (RP), external beam radiation (RT), or implant with or without neoadjuvant androgen deprivation therapy in patients with clinically localized prostate cancer. DESIGN: Retrospective cohort study of outcome data compared using Cox regression multivariable analyses. SETTING AND PATIENTS: A total of 1872 men treated between January 1989 and October 1997 with an RP (n = 888) or implant with or without neoadjuvant androgen deprivation therapy (n = 218) at the Hospital of the University of Pennsylvania, Philadelphia, or RT (n = 766) at the Joint Center for Radiation Therapy, Boston, Mass, were enrolled. MAIN OUTCOME MEASURE: Actuarial freedom from PSA failure (defined as PSA outcome). RESULTS: The relative risk (RR) of PSA failure in low-risk patients (stage T1c, T2a and PSA level < or =10 ng/mL and Gleason score < or =6) treated using RT, implant plus androgen deprivation therapy, or implant therapy was 1.1 (95% confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI, 0.3-3.6), respectively, compared with those patients treated with RP. The RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason score of 7 or PSA level >10 and < or =20 ng/mL) and high-risk patients (stage T2c or PSA level >20 ng/mL or Gleason score > or =8) treated with implant compared with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively. The addition of androgen deprivation to implant therapy did not improve PSA outcome in high-risk patients but resulted in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients. These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10. CONCLUSIONS: Low-risk patients had estimates of 5-year PSA outcome after treatment with RP, RT, or implant with or without neoadjuvant androgen deprivation that were not statistically different, whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant. Prospective randomized trials are needed to verify these findings.     

Clinical aspects of systemic and localized scleroderma

After the skin, the gastrointestinal tract is the most frequently affected organ in systemic sclerosis. Gastrointestinal symptoms already may be present early in the course of the disease and do not necessarily correlate with objective findings. Esophageal dysmotility is not specific for systemic sclerosis but occurs in other connective tissue diseases as well. Peripheral macrovascular disease was shown to be increased in patients with limited cutaneous sclerosis; signs of autonomic dysfunction were found in patients with the CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) variant. Pulmonary involvement was shown to be moderately or severely decreased in 40% of a large cohort of scleroderma patients. In one study, no support was found for the association between pulmonary involvement and gastroesophageal reflux. Peripheral nerve involvement is often subclinical and might be associated with anti-U1-RNP and anti-topoisomerase I antibodies. Internal organs are seldomly affected in localized scleroderma. When occurring in childhood and involving an extremity, localized scleroderma can cause growth failure, resulting in long-term functional disability.     

Antigen specificity of antihistone antibodies in localized scleroderma

BACKGROUND AND DESIGN: Recently, we detected antihistone antibodies (AHAs) in patients with localized scleroderma. However, the exact antigen specificity of AHAs in this disease is still unknown. Therefore, we determined the reactivity of AHAs with five individual histones and the correlation of AHAs with rheumatoid factor in localized scleroderma by means of enzyme-linked immunosorbent assay. Twenty patients with localized scleroderma who had IgG and/or IgM AHAs, as determined by enzyme-linked immunosorbent assay, were examined. These patients were classified into the following three subgroups: patients with generalized morphea (n = 11), patients with linear scleroderma (n = 6), and patients with morphea (n = 3). RESULTS: In generalized morphea, IgG AHAs strongly reacted with histones H1, H2A, and H2B; and IgM AHAs strongly reacted with H1 and H2B, as determined by means of enzyme-linked immunosorbent assay. The pattern of reactivity in linear scleroderma and morphea was similar to that in generalized morphea. A homogeneous immunofluorescent pattern on HEp-2 cells, which was produced by localized scleroderma sera, was completely abolished by absorption with total histones. By employing a latex agglutination test, IgM rheumatoid factor was detected in 60% of the 20 patients with localized scleroderma and at a frequency of 82% in those with generalized morphea. However, an absorption test of rheumatoid factor activity with human IgG revealed no cross-reactivity of AHAs with rheumatoid factor. CONCLUSIONS: Our data suggest that AHAs in localized scleroderma are directed against native chromatin, since H1, H2A, and H2B occupy a relatively exposed portion of chromatin.     

Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: radiation port scleroderma

OBJECTIVES: Analysis of an experience in treating girls with dysfunctional voiding with an outpatient pelvic-floor therapy consisting of voiding and drinking schedule, pelvic-floor relaxation biofeedback, instructions on toilet behavior, and uroflowmetry. METHODS: The files of 50 girls (between 6 and 13 years of age) with urodynamically proven dysfunctional voiding who participated in the training program were analyzed retrospectively. Thirty-five girls received anticholinergics during the entire course of the training. The long-term absence of diurnal incontinence was used as the criterion for the success of the therapy. The duration of treatment before reaching this success was used as a parameter to measure the intensity of therapy. For a portion of the study group, a comparison is made with the duration of the preceding therapies to demonstrate indirectly the cumulative effect of the pelvic-floor therapy. RESULTS: Forty-six girls (92%) normalized their flow and bladder capacity after therapy and saw their daytime incontinence disappearing. All of these girls achieved this result in a maximum of 18 sessions within a 6-month period. At the follow-up examination after 6 months, five of the girls had relapsed (10%), which brings the ultimate success after 6 months of follow-up to 82%. CONCLUSIONS: Pelvic-floor therapy seems to be a reasonable and meaningful component in the treatment of bladder dysfunction in which detrusor-sphincter dyscoordination plays a role.     

High-dose therapy with fluconazole > or = 800 mg day-1

Fluconazole dosages greater than 800 mg day-1 have been reported in about 900 patients treated for candidemia, oropharyngeal candidiasis and cryptococcal meningitis in HIV-infected patients, and for initial therapy of endemic mycoses. In patients with life-threatening infections caused by Candida spp., Cryptococcus neoformans and Coccidioides immitis, results of a limited number of dose-finding trials with non-neutropenic and HIV-infected patients show dose-dependent responses. These study results indicate that higher daily doses of fluconazole than are currently approved for these indications are well tolerated and tend to provide better clinical efficacy in selected patient populations. An excellent safety profile of dosages up to 2000 mg day-1 and linear predictable pharmacokinetics up to 1600 mg day-1 appear to justify further clinical investigations to better determine the optimum dosage and duration of treatment.     

Bronchiolitis obliterans in a patient with localized scleroderma treated with D-penicillamine

D-penicillamine-associated bronchiolitis obliterans (BO) is a rare but well-known pulmonary complication in patients with rheumatoid arthritis or progressive systemic sclerosis. It has been assumed that in most, if not all cases, BO is a complication of the underlying disease rather than a side-effect of treatment. We report the case of a 46 year old man with scleroderma localized to his lower legs (morphea), who received a daily dose of 750 mg D-penicillamine. During the treatment of 1 yr duration, he developed progressive shortness of breath due to a worsening obstructive ventilatory defect suggesting BO, which was confirmed by surgical lung biopsy (constrictive BO). Bronchial obstruction progressed over the next 5 yrs and did not respond to corticosteroids. The patient finally underwent a successful single left lung transplantation. The histological features of constrictive BO were confirmed in the explanted lung. This observation suggests that D-penicillamine may induce bronchiolitis obliterans in the absence of a systemic connective tissue disease.     

Co-morbidities and survival of men with localized prostate cancer treated with surgery or radiation therapy

PURPOSE: We determined the impact of preexisting co-morbidities on survival of men with clinical stages T1b and T2NXM0 prostate cancer treated with surgery or radiation therapy. MATERIALS AND METHODS: A weighted co-morbidity score was determined for 276 consecutive men treated with surgery (138) or radiation therapy (138) at a Veterans Affairs medical center and was correlated with actuarial freedom from death due to co-morbid disease. RESULTS: After a median potential followup of 7.0 years 91 patients (33%) died of co-morbid disease and 20 (7%) died of cancer related causes. There were highly significant correlations between actuarial survival and weighted co-morbidity (p < 0.000001), and the 10-year actuarial survivals in men with no or severe co-morbidities were 66 and 9%, respectively. Associations between patient age and co-morbidity score were highly significant (p < 0.0001). The age adjusted risk of co-morbid death was 5.7 times greater in men with severe compared to no co-morbidities. There were also significant correlations between actuarial survival and weighted co-morbidity among patients treated with surgery (p = 0.02) and radiation therapy (p = 0.0002). Patient age and severity of co-morbidities were significantly greater among men treated with radiation therapy compared to surgery, and age adjusted risk of co-morbid death among men with a co-morbidity score of 1 was 3.8 times greater among men treated with radiation therapy (p = 0.025). CONCLUSIONS: Cancer related deaths are unusual within 5 to 10 years after surgery or radiation therapy in men with stages T1b and 2 prostate cancer. The risk of death during this interval is directly related to the severity of co-morbid conditions, which should be factored in an individual when assessing the advisability of therapeutic intervention. Since patient co-morbidities impact all cause survival, quantitative assessment of co-morbidities using validated instruments offers a method to control partially for the variabilities of health status among men receiving different treatments for localized prostate cancer.     

Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma

The electrophysiological properties of neurons of the medial septal nucleus and the nucleus of the diagnonal band of Broca (MS/DB) were studied using intracellular methods in urethane-anesthetized rats. Three types of rhythmically bursting neurons were identified in vivo on the basis of their action potential shapes and durations, afterhyperpolarizations (AHPs), membrane characteristics, firing rates and sensitivities to the action of muscarinic antagonist: (1) Cells with short-duration action potentials and no AHPs (2 of 34 rhythmic cells, 6%) had high firing rates and extremely reliable bursts with 6-16 spikes per theta cycle, which were highly resistant to scopolamine action. (2) Cells with short-duration action potentials and short-duration AHPs (8 of 34 rhythmic cells, 24%) also had high firing rates and reliable bursts with 4-13 spikes per theta cycle, phase-locked to the negative peak of the dentate theta wave. Hyperpolarizing current injection revealed a brief membrane time constant, time-dependent membrane rectification and a burst of firing at the break. Depolarizing current steps produced high-frequency repetitive trains of action potentials without spike frequency adaptation. The action potential and membrane and characteristics of this cell type are consistent with those described for GABAergic septal neurons. Many of these neurons retained their theta-bursting pattern in the presence of muscarinic antagonist. (3) Cells with long-duration action potentials and long-duration AHPs (24 of 34 rhythmic cells, 70%) had low firing rates, and usually only 1-3 spikes per theta cycle, locked mainly to the positive peak of the dentate theta rhythm. Hyperpolarizing current injection revealed a long membrane time constant and a break potential; a depolarizing pulse caused a train of action potentials with pronounced spike frequency adaptation. The action potential and membrane properties of this cell type are consistent with those reported for cholinergic septal neurons. The theta-related rhythmicity of this cell type was abolished by muscarinic antagonists. The phasic inhibition of "cholinergic" MS/DB neurons by "GABAergic" MS/DB neurons, followed by a rebound of their firing, is proposed as a mechanism contributing to recruitment of the whole MS/DB neuronal population into the synchronized rhythmic bursting pattern of activity that underlies the occurrence of the hippocampal theta rhythm.     

High-dose intravenous steroid pulse therapy in thyroid-associated ophthalmopathy

MIcrospheres containing diclofenac sodium (DS) were prepared using carboxymethylcellulose (CMC) as the main support material (1.0, 2.0, 3.0% (w/v)) and aluminum chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit S-100, efficiency, % yield value, particle sizes an in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used.     

High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma

PURPOSE: Women with locally unresectable and inflammatory breast carcinoma (IBC) have an approximately 30% 5-year disease-free survival (DFS) rate with conventional multimodality therapy. A short but dose-intensive multimodality phase II trial was designed in an attempt to improve outcome in stage IIIB disease. Mastectomy was performed after high-dose therapy to evaluate pathologic response to treatment. METHODS: Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support. Local therapy consisted of mastectomy and radiotherapy. Tamoxifen (5 years) was begun if the patient was estrogen receptor-positive (ER+). RESULTS: Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mastectomy before any systemic therapy (seven with pathologic IBC, three with residual tumor after mastectomy). Eighty percent received full-dose doxorubicin with 60% on schedule. Clinical response rates to induction were 15% complete response (CR), 5% very good partial response (VGPR), 59% partial response (PR), and 21% minor response (MR)/stable disease (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CTCb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30-month DFS is estimated at 100%, 70%, and 38%, respectively. Those with zero, one to three, or > or = four positive nodes at axillary dissection had a median DFS of 31, 18, and 13 months, respectively. CONCLUSION: This short but dose-intensive multimodality approach for stage IIIB breast carcinoma is feasible with encouraging results to date.     

A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus

BACKGROUND: Despite well-established surgical approaches, the prognosis for patients with squamous cell carcinoma of the esophagus remains dismal. To assess the benefit of adjuvant chemotherapy and radiation therapy (CRT), a randomized trial with and without sequential preoperative CRT was undertaken; CRT combined 20 Gy and two courses of 5-FU and cisplatin. METHODS: Patients were included on the basis of the following criteria: squamous cell carcinoma of the esophagus, younger than 70 years of age, World Health Organization status below 2, estimated survival time greater than 3 months, and no previous treatment for the cancer. Patients were not included if they had experienced a loss in body weight greater than 15% or had tracheoesophageal fistula, metastases, or uncontrollable infection. RESULTS: Eighty-six patients thus fulfilled the criteria for inclusion (41 CRT, 45 non-CRT). The groups were well-matched for age, sex, tumor location, size, and grade. Operative mortality was 8.5% and 7%, respectively, for each group with a 27-day hospital stay for both groups. Long-term survival was not significantly different, with 47% of both groups alive at 1 year. CONCLUSIONS: The authors concluded that this neoadjuvant treatment did not change operative mortality or survival time for patients with squamous cell carcinoma of the esophagus.