Route of contact sensitization and in vitro lymphocyte transformation.

A guinea pig skin extract conjugate with dinitrofluorobenzene elicited significant in vitro transformation of cultured lymphnode lymphocytes from 19 of 27 guinea pigs sensitized by footpad injection of dinitrochlorobenzene in Freund's complete adjuvant, as compared to only 1 of 26 guinea pigs topically sensitized to dinitrochlorobenzene. Topically sensitized guinea pigs appear to be more appropriate models for contact allergy in man than guinea pigs sensitized by other methods. Other sensitization procedures are likely to produce more heterogeneous forms of sensitization, with features of contact allergy, tuberculin-type allergy, antibody-mediated hypersensitivity and cutaneous basophile hypersensitivity.

The role of Langerhans cells in allergic contact hypersensitivity. A review of findings in man and guinea pigs.

Evidence in favor of a role for Langerhans cells in contact allergic hypersensitivity reactions has been reviewed. This includes mononuclear cell to Langerhans cell apposition and damage to some Langerhans cells at sites of specific challenge to a variety of contact allergens. Such apposition occurs in actively sensitized patients and guinea pigs and in passively sensitized guinea pigs. In addition, in passively sensitized guinea pigs Langerhans cells circulate in dermal vessels resembling lymphatics and are much increased in the dermis after challenge with the contact allergen. These observations, together with the existing knowledge that Langerhans cells occur in the lymph nodes and thymus, suggest that these cells may be involved not only in contact allergic reactions but also in other immunologic reactions, particularly in cell-mediated reactions in the skin.

The role of Langerhans cells in allergic contact hypersensitivity. A review of findings in man and guinea pigs. 1976.

Evidence in favor of a role for Langerhans cells in contact allergic hypersensitivity reactions has been reviewed. This includes mononuclear cell to Langerhans cell apposition and damage to some Langerhans cells at sites of specific challenge to a variety of contact allergens. Such apposition occurs in actively sensitized patients and guinea pigs and in passively sensitized guinea pigs. In addition, in passively sensitized guinea pigs, Langerhans cells circulate in dermal vessels resembling lymphatics and are much increased in the dermis after challenge with the contact allergen. These observations, together with the existing knowledge that Langerhans cells occur in the lymph nodes and thymus, suggest that these cells may be involved not only in contact allergic reactions but also in other immunologic reactions, particularly in cell-mediated reactions in the skin.

Concurrent carboplatin, etoposide and thoracic radiation for poor-risk stage III non-small-cell lung carcinoma: a pilot study.

PURPOSE: A pilot study was conducted to assess the tolerance and efficacy of concurrent carboplatin, etoposide, and thoracic radiation in poor-risk patients with Stage III non-small-cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Patients had Stages IIIA/IIIB NSCLC and were ineligible for available clinical trials employing cisplatin-based chemoradiation due to one or more protocol-defined poor-risk factors or concomitant medical conditions. Treatment consisted of thoracic radiation, 1.8 to 2 Gy daily, to the primary tumor and regional lymph nodes to a total dose of 61 Gy. Concurrently, patients received carboplatin 200 mg/m2/day intravenously on days 1, 3, 29, and 31, and etoposide 50 mg/m2/day intravenously on days 1-4 and 29-32. Response was assessed by chest computed tomography (CT) 4 weeks after treatment was completed. RESULTS: A total of 26 patients were enrolled and 23 of these patients, including 11 with Stage IIIA and 12 Stage IIIB NSCLC, were eligible and assessable. Ninety-six percent (96%) of the patients completed the two planned courses of chemotherapy, and 87% completed the planned chest radiation. Grade III/IV toxicities included neutropenia in nine patients (39%), thrombocytopenia in five (22%), esophagitis in seven (30%), and nausea in two (9%). One patient died of a pulmonary embolism during treatment, and another died of complications due to a tracheoesophageal fistula. Four patients (17%) achieved a complete response and 16 (70%) a partial response, yielding an overall response rate of 87%. The median survival was 12 months, and the 2-year actuarial survival was 40%. CONCLUSION: This treatment regimen was well tolerated, with promising response and survival in poor-risk patients with Stage III NSCLC. These results are being validated in a Phase II trial conducted by the Southwest Oncology Group.

Improved methods for determination of variability in patient positioning for radiation therapy using simulation and serial portal film measurements.

Variability in patient positioning was determined by analyzing simulation and portal film measurements for 318 portals in 51 patients treated with external beam radiotherapy to the head and neck. Several indicators of error in patient positioning were examined: random error, a measure of the deviation of all portal films from the average portal film position, systematic error, a measure of the difference between the average portal film and the simulation film, and total uncertainty, a measure of the overall deviation, including both random and systematic uncertainties. The median differences noted were 0.4 cm, 0.6 cm, and 0.7 cm, for Random Error, Systematic Error, and Total Uncertainty, respectively. The treatment fields analyzed in this study show a substantial treatment-to-treatment and simulation-to-treatment variability in patient positioning. The methods described provide an improved means for the systematic analysis of variability in patient positioning.

Defining treatment margins for six field conformal irradiation of localized prostate cancer.

PURPOSE: To define the "ideal margins" to be used for the delivery of six-field conformal radiotherapy for localized prostate cancer. METHODS AND MATERIALS: For a typical patient, 3-D based 6-field conformal treatment plans were generated using uniform margins ranging from 0.5-2.5 cm (in 0.25 cm increments). In a step-wise fashion the minimum margins required to encompass the gross tumor volume within the 90% isodose shell were identified. Additional margins were then added to account for extracapsular penetration, setup and patients movement error as well as for organ movement. Assumptions about the relative tolerance of surrounding normal tissues were also incorporated into the final decisions regarding margins. RESULTS: For the various areas of interface, between the prostate and surrounding normal tissues "ideal margins" varied from 0.75-2.25 cm. CONCLUSION: The use of nonuniform "ideal margins" appears to insure adequate coverage of the tumor, while minimizing the volume of surrounding dose limiting normal tissues irradiated. This approach should in theory improve the tumor control and complication probabilities compared to using conventional treatment techniques and to using a 6-field conformal technique with uniform margins.

Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation.

PURPOSE: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. METHODS AND MATERIALS: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). RESULTS: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or bone-equivalent phantom. CONCLUSIONS: The impact of radiation therapy on plate preservation after mandibular reconstructive surgery using a titanium plate may be dependent on the timing of RT relative to surgery. Significantly more mandibular reconstruction plates were lost when the involved mandible received RT in the perioperative period than when RT was delivered beyond 10 months from surgery or when no RT was given. The use of alloplastic implants such as titanium plates in conjunction with myocutaneous flap coverage for mandibular reconstruction is attractive because it allows immediate reconstruction of the defect and promotes a good functional and cosmetic result; however, administration of perioperative RT may result in a higher plate failure rate.

Immobilization improves the reproducibility of patient positioning during six-field conformal radiation therapy for prostate carcinoma.

PURPOSE: To determine the magnitude of patient positioning errors associated with six field conformal therapy for carcinoma of the prostate, and to assess the impact of alpha-cradle immobilization on these errors. METHODS AND MATERIALS: The records of 22 patients, treated at two of the treatment facilities within our department, using computed tomography-planned conformal six field therapy for carcinoma of the prostate, were reviewed. At one facility (UCD), patients were routinely treated with immobilization, while at the other (UCSF) no rigid immobilization was used. Portal films of patients treated at both facilities were subsequently reviewed, and the deviation of each portal from the simulation film was determined (simulation-to-treatment variability). In addition, for each patient, the average deviation of each portal film from the average portal film (treatment-to-treatment variability) was determined. RESULTS: The mean and median simulation-to-treatment variability was 0.4 cm for those patients treated with immobilization, versus 0.6 cm for those treated without immobilization. The 90th percentile of simulation-to-treatment variability was 0.7 cm for those patients treated with immobilization, versus 1.1 cm for those not immobilized. There was a significant reduction in the number of portals observed with errors of > or = 0.50 cm (132/201 vs. 37/87, 66% vs. 43%; p < 0.001), 0.75 cm (184/201 vs. 59/87, 92% vs. 68%; p < 0.001), and 1.0 cm (196/201 vs. 74/87, 98% vs. 85%; p < 0.001) for patients treated with immobilization. There was also a significant reduction in the number of patients with treatment-to-treatment variability > or = 0.5 cm (1/10 vs. 8/12; p = 0.01) for patients treated with immobilization. CONCLUSION: The use of immobilization devices significantly reduces errors in patient positioning, potentially permitting the use of smaller treatment volumes. Immobilization should be a component of conformal radiation therapy programs for prostate carcinoma.

Should patients with post-resection locoregional recurrence of lung cancer receive aggressive therapy?

The outcome of thirty-seven patients with a post-resection locoregional recurrence of non-small cell lung cancer treated with radiation therapy alone between 1979 and 1989 was compared to that of 759 patients with unresected non-small cell lung cancer also treated with standard radiation during the same period. Each patient's locoregional recurrence was staged using the current American Joint Committee on Cancer staging system. Comparison of pretreatment characteristics between the two groups, including age, sex, extent of weight loss, performance status, stage, and histologic subtype revealed fewer patients with greater than 5% weight loss (35 vs. 47%, p = 0.04) and more cases with squamous histology (54 vs. 28%, p = 0.01) among the patients with locoregional recurrences than those with newly diagnosed lesions. Over 80% of both groups had clinical stage III lesions. The median radiation doses were 56 and 59 Gy for recurrent and newly diagnosed cases (p = NS). For the patients with locoregional recurrences, the median time from resection to recurrence was 13 months (range: 3-118 months), and the recurrences were predominantly nodal in 25 cases, chest wall/pleural in four and at the bronchial stump in eight. When measured from the date of documented recurrence, the median survival time and 2-year actuarial survival rate of the patients with recurrent lesions were 12 months and 22%, as compared to 12 months and 26% for the newly diagnosed patients (p = NS). Freedom from documented locoregional tumor progression at 2 years was 30% for both groups. Patients with bronchial stump lesions had superior survival to those with nodal or chest wall recurrences, with a median survival time of 36 versus 9 months. A therapeutic approach to selected patients with post-resection locoregional recurrence of non-small cell lung cancer equally aggressive to that for newly diagnosed lung cancer patients is justified by these results, especially for patients with bronchial stump recurrences.

Adverse influence of younger age on outcome in patients with non-small cell lung carcinoma (NSCLC) treated with radiation therapy (RT) alone.

Treatment outcome of 63 patients younger than 50 years of age initiated on a course of once-daily definitive radiation therapy without concurrent or preirradiation chemotherapy for clinical Stages I-III unresected non-small cell lung carcinoma from 1978 to 1988 was compared to the outcome of 695 patients over the age of 50. Follow-up ranged from 24-110 months with follow-up until death in 88% of patients. The actuarial overall survival rate for all patients was 22% at 2 years with a median survival time of 11.5 months. Patients less than 50 and greater than or equal to 50 years old were similar in male:female ratio, distribution of histologic subtype, performance status, and extent of weight loss. Poorly differentiated histologic grade was more prevalent among the younger patients (59% vs 41%, p = .005). Ninety-four percent of younger patients and 86% of older patients had clinical stage III disease (p = NS). Survival was significantly worse for patients who were younger than 50 years old (p = .05), with a median survival time of 7.8 months. Median survival time for those patients 50 years of age or older was 12.4 months. Poorer survival outcome among young patients was most pronounced among patients with unfavorable characteristics of poor performance status (greater than or equal to 2) or weight loss (greater than 5%) (p = .002). Distant failure (p = .029) and brain failure (p = .003) as initial site of relapse was more common among younger patients. Among young patients, poor histologic grade was associated with both distant failure (p = .003) and brain metastasis (p = .002). The difference in distribution of histologic grade, incidence of distant failure, particularly in the brain, and poorer survival outcome among patients less than 50 may be indicative of more aggressive tumor behavior in the younger patients. These results indicate that patients less than 50 may require alternate treatment strategies. Age should be considered a stratification variable in non-operative randomized trials of non-small cell lung carcinoma which include patients with non-favorable characteristics.

Diethyl 3,6-dihydro-2,4-dimethyl-2,6-methano-1,3-benzothiazocine-5,11- dicarboxylates as calcium entry antagonists: new conformationally restrained analogues of Hantzsch 1,4-dihydropyridines related to nitrendipine as probes for receptor-site conformation.

The pharmacological activity of rigid analogues of 1,4-dihydropyridine calcium entry antagonists 9-16 is demonstrated by dose-dependent inhibition of the calcium contraction in depolarized rat aortic strips and by a [3H]nitrendipine binding assay in using cardiac sarcolemmal membranes. From the results, a model is proposed as the receptor-bound conformation of the dihydropyridine calcium entry antagonists.

p53 and bcl-2 immunohistochemical alterations in prostate cancer treated with radiation therapy.

OBJECTIVES: Radiation therapy is definitive treatment for localized prostate cancer. It causes cellular deoxyribonucleic acid (DNA) damage, which, if irreparable, results in apoptosis or programmed cell death. Overexpression of mutant p53 and/or bcl-2 proteins prolongs cell survival despite exposure to damaging agents. We examined whether abnormal expression of either gene could help to explain radiation therapy failures in prostate cancer. METHODS: Archival tissue from patients who had failed radiation therapy as treatment for prostate cancer was obtained before and after treatment. These cancer samples were examined immunohistochemically for accumulation of p53 and bcl-2 proteins. Comparison was made with specimens from patients who had no evidence of recurrent or persistent disease at least 3 years following radiation therapy. RESULTS: High rates of p53 immunopositivity were found in the prostate tissue from all groups studied. More patients who had failed radiation therapy were found to have bcl-2 immunopositive specimens than were those without evidence for recurrent disease (41% preradiation and 61% postradiation versus 8%, P <0.05). More patients who failed radiation therapy had both p53 and bcl-2 immunopositive prostate tissue than did those who were treated successfully (32% preradiation and 48% postradiation versus 8%). CONCLUSIONS: bcl-2 immunopositivity, with or without concomitant detection of p53, was found in significantly more cancers of patients who failed radiation therapy. Positive staining for bcl-2 may serve as a marker for determining the radiation sensitivity of a tumor and thus may help to guide treatment options. It is also notable that a high proportion of the prostate cancers examined were immunopositive for p53.

Effect of washing closed head and neck wounds on wound healing and infection.

A group of 100 patients were compared with 100 control patients. Both groups had either traumatic or surgically incised clean wounds of the head and neck. The groups were similar except that the 100 test patients were allowed to wash their head and neck wounds with soap and water within hours after the repair, while the control group kept their wounds dry until all of the sutures were removed. On the basis of this study, we believe that allowing patients to wash their wounds and bathe routinely as early as 8 hours after wound closure hs no effect on wound or infection. We believe that good technique during surgery for incision or laceration closure is much more important than any manipulation of the wound or of the general body systems.

Capromab Pendetide imaging of prostate cancer.

Capromab Pendetide imaging illustrates the successful translation of monoclonal antibody technology from the laboratory to the clinic. It provides a means of identifying otherwise occult soft tissue metastases in patients with adenocarcinoma of the prostate. When utilized with other clinical, pathological and laboratory findings, Capromab Pendetide imaging enables more accurate disease staging and monitoring than is afforded by other imaging modalities such as CT and MRI. In the primary disease setting Capromab Pendetide imaging should be reserved for use in patients with negative bone scans who are at high risk for metastatic disease based on such factors as advanced clinical stage, high Gleason score and significantly elevated serum PSA or alkaline phosphatase. Due to low sensitivity for small-volume disease, a negative Mab scan may not eliminate the need for a staging lymph node dissection but should encourage further consideration of local treatment options. Capromab Pendetide should be used with caution in patients at low risk for metastatic disease. Positive scan findings in low risk patients should be confirmed before altering the treatment plan since some false positive scans should be anticipated in a population with low disease prevalence. Capromab Pendetide imaging has not been shown to be reliable in determining the local extent of the primary tumor but new techniques involving co-registration of SPECT and CT images show promise in this regard. In the patient with recurrent disease following primary therapy, the predictive value of Capromab Pendetide imaging of the prostate or prostate fossa is limited, particularly following RT. Its more important role in this setting is to identify lymph node metastases in the high risk patient with a negative bone scan who might otherwise be a candidate for local salvage therapy. A large prospective study is needed for confirmation, but preliminary data suggest that Capromab Pendetide imaging is helpful in identifying those patients with PSA elevation after radical prostatectomy who are most likely to benefit from salvage RT. As with any imaging technique, Capromab Pendetide has strengths and weaknesses that must be understood to maximize patient benefit by utilizing the scan in clinical settings where it is most likely to be useful and least likely to be misleading. Capromab Pendetide is a technically demanding procedure best performed and interpreted at sites with experience and expertise.

Tinea pedis isolates.

An attempt was made to test environmental factors that may influence acquisition of athlete's foot from public places.

Applications of asymmetric collimation on linear accelerators.

Frequency of use of asymmetric collimation (AC) at an academic radiation oncology center equipped with AC-capable linear accelerators was determined, and the type of use was cataloged. Records of patients beginning radiation treatment at U.C. Davis Cancer Center within a 3-month period (3/1/92 to 5/31/92) were reviewed. Forty-seven percent of 102 patients and 56% of 123 courses of treatment involved AC. Six common uses of AC were identified: beam-split field matching, planned boosts, other field size changes, adjustments to match divergent fields, matchline feathering, and opposed tangential fields. This study demonstrates that asymmetric collimation is a useful and powerful clinical treatment tool with widespread applications to radiation therapy.

Monoclonal antibody imaging of occult prostate cancer in patients with elevated prostate-specific antigen. Positron emission tomography and biopsy correlation.

The utility of monoclonal antibody (MAb) imaging for detection of occult recurrent prostate cancer was investigated in 14 patients with elevated serum prostate-specific antigen at least 3 months after therapy. All were imaged with capromab pendetide (CYT-356) and subsequently had biopsies of the prostate bed. Ten also had PET scans with F-18 fluorodeoxyglucose. Ten MAb scans were positive for tumor in the prostate bed and eight showed lymph node metastases. Six of the seven patients with positive biopsies had positive MAb scans, one had a negative scan. Three of the seven patients with negative biopsies had negative MAb scans, four had positive scans. Of the six patients with positive biopsies who had PET scans, one was positive, five were negative. Two of four patients with negative biopsies had negative positron emission tomography scans, two were positive. MAb imaging is superior to PET scan for identifying recurrent disease in the prostate bed. Assuming no false-negative biopsies, the positive predictive values for MAb and PET scan are 60% and 33%, negative predictive values are 75% and 29% and sensitivities are 86% and 17%. Additional investigation is necessary to determine if MAb uptake in lymph nodes is predictive of metastatic disease.

American College of Radiology Appropriateness Criteria(®)--locally advanced (high-risk) prostate cancer.

The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. This review focuses on locally advanced prostate cancer and the evidence for treatment outcomes, both toxicity and efficacy, across the three major treatment modalities of external beam radiotherapy, brachytherapy and surgery. Only data that could pass contemporary quality metrics were used to form this report. This body of literature suffers from an absence of trials prospectively comparing therapies for efficacy and a lack of long-term prospective comparisons of toxicity. Upon review of these data, the authors concluded that there are several acceptable methods for the treatment of locally advanced prostate cancer that is highly dependent of the patient's clinical (both prostate cancer-specific and comorbidity-specific) parameters at diagnosis.