PBLs of early breast carcinoma patients with a high nuclear grade tumor unlike PBLs of cervical carcinoma patients do not show a decreased TCR zeta expression but are functionally impaired.

Peripheral blood lymphocytes (PBLs) of patients with cervical intraepithelial neoplasia (CIN), cervical carcinoma, or early breast carcinoma were tested for the expression of T cell receptor zeta chain (TCR zeta) and CD16 zeta chain and production of interferon-gamma (IFN gamma) and interleukin (IL) 10. We found that in all patients with CIN and invasive cervical carcinoma, PBLs showed a reduced TCR zeta and CD16 zeta expression and a significant down-regulation in IFN gamma production (a T helper 1 cytokine) after anti-CD3 stimulation. However, the IL 10 secretion (a T helper 2 cytokine) was not diminished after anti-CD3 stimulation. This indicates that only T helper 1 cells are affected by the down-regulation of the TCR zeta chain expression. We also analyzed PBLs of 12 patients with early breast carcinoma. In these patients, we found TCR zeta and CD16 zeta expression down-regulation in 2 of 12 patients. Six of 12 patients had an enhanced TCR zeta expression. The enhanced TCR zeta expression correlated with a reduced IFN gamma expression after anti-CD3 stimulation. These data show that in general PBLs of early breast carcinoma patients, unlike those of cervical carcinoma patients, do not show a decreased TCR zeta expression. However, a functional impairment of T cells was observed in the subgroup of early breast carcinoma patients with a high nuclear grade of their tumor.

Factors that influence biochemical failure after radiation therapy for stage T1c prostate cancer.

More patients are now being diagnosed with nonpalpable prostate cancer after a needle biopsy is performed for an elevated prostate-specific antigen (PSA) level (stage T1c). The purpose of this study was to identify prognostic factors that are associated with biochemical failure after definitive external beam radiation therapy. This study included 75 patients with the diagnosis of T1c prostate cancer who were referred to four radiation oncology centers in the West Chicago area from 1992 to 1995. All patients were treated with megavoltage external beam radiotherapy to doses between 66 and 70 Gy. Biochemical failure was defined as three consecutive rising PSA values of at least 10% of the prior reading in posttreatment serial measurements. The mean age of the patients was 72 years. The mean follow-up was 1.7 years (range, 1-3 1/2 years). Of the 75 patients, 72 (96%) are clinically with no evidence of disease, three of the 75 are alive with disease, and 60 (80%) remain biochemically free of disease (bNED). The significant factors for bNED status were an initial PSA level of <15 ng/ml (p = 0.0001), achievement of a posttreatment nadir PSA level of < or = 1.5 ng/ml (p = 0.0001), and a Gleason score of <6 (p = 0.034). Multisextant involvement with tumor or bilobar disease was not significant. On multivariate analysis, an initial PSA level of <15 ng/ml (p = 0.0001), Gleason score of <6 (p = 0.02), and nadir PSA level of < or = 1.5 ng/ml (p = 0.03) were significant predictors of bNED survival. Men with T1c prostate cancer comprise a heterogeneous group. Patients with a high PSA level (>15 ng/ml) and high Gleason score (>6) are at increased risk for biochemical failure. Failure to achieve a posttreatment nadir PSA level of < or = 1.5 ng/ml is a predictor of ultimate biochemical failure.

Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial.

PURPOSE: To determine the toxicity and prognosis of patients with relapsed and refractory diffuse aggressive non-Hodgkin's lymphoma (NHL) who underwent an autologous bone marrow transplant (ABMT) using augmented preparative regimens, treated in a major cooperative group setting, and to examine prognostic factors for outcome. PATIENTS AND METHODS: Ninety-four patients with either chemosensitive (50 patients) or chemoresistant (44 patients) relapse, including 22 who failed induction chemotherapy, were treated with high-dose cyclophosphamide and etoposide with total-body irradiation (TBI) (67 patients) or an augmented carmustine (BCNU), cyclophosphamide, and etoposide (BCV) preparative regimen (27 patients) and an ABMT at 16 Southwest Oncology Group (SWOG) transplant centers. All relapsing patients were required to undergo a minimum of two courses of salvage therapy to determine chemosensitivity before transplant. Overall (OS) and progression-free survival (PFS) were determined and a Cox regression model was used to assess potential prognostic variables. RESULTS: Of the 94 eligible patients, there were 10 (10.6%) deaths before day 50 posttransplant because of infection (six deaths), hemorrhagic alveolitis (three deaths), or bleeding (one death). The median 3-year PFS and OS for the entire group was 33% and 44%. For those with chemosensitive disease the PFS and OS were 42% and 55%, whereas for those with chemoresistant disease the PFS and OS were 22% and 29%. The PFS and OS for those failing induction chemotherapy were 27% and 32%. The relapse rates within the first 3 years for the chemosensitive relapse, chemoresistant, and induction failure groups were 61%, 40%, and 59%, respectively. For both PFS and OS, only disease status at transplant was a significant factor in the multivariate Cox model. CONCLUSION: These results single institutional pilot trials exploring augmented preparative regimens. Patients undergoing transplantation for resistant disease, particularly those failing induction chemotherapy, appear to have an improved prognosis as compared with reports using standard preparative regimens. Therapies other than manipulation of standard preparative regimens appear to be required to decrease relapses following autotransplantation.

Paclitaxel is only a weak radiosensitizer of human cervical carcinoma cell lines.

Two human squamous cell cervical carcinoma cell lines, C-33A (HTB 31) and MS751 (HTB 34), were exposed to either paclitaxel alone or paclitaxel for 24 hr followed by graded doses of Cs-137 radiation. Each was then analyzed for both clonogenic survival and alterations to cell cycle progression. No radiosensitization or affect on the cell cycle was seen using 1 x 10(-9) M paclitaxel. Each line was equally sensitive to the drug with approximately 50% cell lethality seen after 1 x 10(-8) M of paclitaxel. This concentration of paclitaxel also produced substantial G2M arrest, seen immediately after drug exposure and lasting up to 2 days. Gamma radiation delivered during the time of G2M arrest showed only a small degree of radiosensitization by paclitaxel for the relatively radioresistant MS751 line at 4 Gy (SF4 = 16.0 +/- 3.2% --> 5.7 +/- 1.1%, P = 0.049) but no sensitization using radiation doses of conventional fraction size [sensitizer enhancement ratios 1.1 (0.80-1.40) and 1.3 (0.95-1.65) for the C-33A and MS751 cell lines, respectively]. It is concluded that paclitaxel produces only a modest radiosensitization effect, indicating that this compound will have limited benefit as a radiosensitizer for the treatment of cervical cancer.

The variation of inguinal lymph node depth in adult women and its importance in planning elective irradiation for vulvar cancer.

BACKGROUND: The Gynecologic Oncology Group (GOG) protocol #88 reported an 18.5% failure in inguinal lymph nodes of patients with vulvar cancer whose groins were treated with radiation alone. This high failure rate may be due to the study design. METHODS: In this study, the depths of inguinal lymph nodes were evaluated with computed tomography (CT) scans in 100 adult women without inguinal adenopathy or prior inguinal surgery. The dose that would have been delivered to the inguinal lymph nodes of these patients was determined using isodose curves constructed according to the guidelines in GOG protocol #88. RESULTS: Only 18% of women had all inguinal lymph nodes measured at a depth of 3 cm or less. CONCLUSIONS: More than one-half of all women in this study would have received less than 60% of the prescribed radiation dose because their inguinal lymph nodes were deeper than 5 cm, if the depth of their inguinal lymph nodes had not been measured before therapy.

DNA ploidy, proliferation index, grade, and stage as prognostic factors for vulvar squamous cell carcinomas.

DNA analysis by flow cytometry has been reported to be a useful prognostic technique for a variety of malignant tumors. The goal of this study was to examine DNA ploidy status and proliferation index as potential predictors of recurrence and survival for patients with squamous cell vulvar carcinomas. The DNA ploidy, percentage of cells in the S-phase of the cell cycle, stage, and histologic grade were analyzed in 42 patients. Flow cytometry was performed on archival paraffin-embedded tissue. The histologic specimens were reviewed by a single pathologist. Thirty-four tumors (81%) were diploid and eight (19%) demonstrated an aneuploid peak. The percentage of cells in the S-phase (proliferation index) was calculated for all patients. The 5-year survival rate was 68% for diploid tumors and was 75% for aneuploid tumors. The difference between these rates was not statistically significant (P < or = 0.65). S-phase fraction was also not a useful predictor for recurrence or overall survival. FIGO stage and histologic grade were accurate predictors for both recurrence and 5-year survival. Multiple predictor analysis using stage, grade, ploidy status, and proliferation index did not identify any subgroup which would predict recurrence better than FIGO stage and grade. DNA ploidy and S-phase fraction analysis do not appear to be clinically useful prognostic factors for vulvar squamous cell carcinomas.

The incidence of thyroid carcinoma in Hashimoto's thyroiditis.

The incidence of thyroid carcinoma in Hashimoto's thyroiditis has been a widely debated issue. Previous authors have reported on this topic by analyzing series of patients with Hashimoto's thyroiditis or patients with thyroid carcinoma, but not both of those populations in the same series. The population consists of a consecutive series of 800 patients operated on for thyroid nodules not associated with a radiation history. Among 161 patients with the diagnosis of thyroid carcinoma, 61 (38%) had coexistent Hashimoto's thyroiditis. In comparison, among 161 sex- and age-matched patients with colloid nodules in the same population, 18 (11%) had Hashimoto's thyroiditis. Furthermore, in the series as a whole, the incidence of Hashimoto's thyroiditis in 423 patients with colloid nodules was 10 per cent. From the perspective of the Hashimoto's thyroiditis population in the same series of 800 thyroidectomies, among 267 patients with Hashimoto's thyroiditis 61 (23%) had coexistent carcinoma. In comparison, among 267 age- and sex-matched patients with colloid nodules there were only ten coexistent carcinomas for an incidence of 4 per cent. The high incidence of carcinoma of the thyroid in Hashimoto's thyroiditis lends credence to the hypothesis that Hashimoto's thyroiditis is a predisposing factor in the development of thyroid carcinoma.

Improvement of vocal cord paresis after thyroidectomy.

Iatrogenic vocal cord paralysis is a well-publicized complication of thyroid and parathyroid operations. Less appreciated is the improvement of vocal cord function after resection of a thyroid or parathyroid tumor. Over the last 22 years, 14 patients presented with vocal cord paresis in the presence of thyroid or parathyroid tumors. Of these 14 patients, nine had complete resolution of paresis following resection of the thyroid or parathyroid tumors: three had a thyroid carcinoma impinging upon the nerve, three had large colloid goiters, two had a follicular adenoma and one had a parathyroid adenoma displacing the nerve. In five of the 14 patients the vocal cord paralysis persisted after operation. In three, the pathology accounted for the vocal cord paralysis and was not amenable to operative improvement: one patient had an unresectable anaplastic thyroid carcinoma, one patient had long-standing idiopathic unilateral vocal cord paralysis, and one patient had laryngeal adenoid cystic carcinoma with thyroid invasion. The fourth patient had an extensive thyroid hemangioma. The paralysis persisted after resection. The fifth patient had long-standing idiopathic vocal cord palsy. A preoperative vocal cord paresis in a patient with thyroid or parathyroid disease does not indicate permanent loss of recurrent nerve function, even in the presence of carcinoma. In this series, vocal cord function was restored in 9 of 10 patients with resectable thyroid or parathyroid tumors.

Parathyroid autotransplantation in forty-four patients with primary hyperparathyroidism: the role of thallium scanning.

Forty-four patients with primary hyperparathyroidism were followed for 18 to 126 months after subtotal or total parathyroidectomy and parathyroid autotransplantation. Indications for autotransplantation included the devascularization of parathyroid glands during concomitant thyroid lobectomy or total thyroidectomy and the excision of the only remaining parathyroid tissue in patients with persistent hyperparathyroidism after previous unsuccessful parathyroidectomies. Before implantation, all parathyroid tissue was histologically evaluated by frozen-section light microscopy with hematoxylin and eosin stain. Fifteen patients had histologically normal implants; to date none of these patients have developed recurrent hyperparathyroidism. Twenty-nine patients had either adenomatous or hyperplastic parathyroid tissue used for implants; two of these patients developed graft-dependent recurrent hyperparathyroidism 4 and 7 years later. In both patients the grafts were preoperatively localized by thallium scanning and their resection restored eucalcemia. One hundred thirty-one patients from 11 series in the current literature had a cumulative incidence of 17.5% for presumed graft-dependent recurrence and a 9.2% incidence of graft excision followed by eucalcemia. In comparison, in the present series the incidence of graft-dependent recurrent hyperparathyroidism in patients with either adenomatous or hyperplastic implants stands at 6.9%. In contrast, in 15 patients with normal parathyroid tissue implants, the incidence was zero.

Primary cardiac osteosarcoma: multidisciplinary aspects applicable to extraskeletal osteosarcoma generally.

An osteosarcoma, primary in the right ventricular epicardium, produced pericardial constriction. Intense activity on technetium-99m bone scintigraphy led to a correct preoperative diagnosis. Biopsy of unrepresentative tissue clouded the diagnosis, and autopsy resolved the issue. Several clinicopathologic correlations are presented. Major therapeutic advances mandate early recognition of extraskeletal osteosarcoma, and the topic is reviewed in regard to cardiac cancers in general. The need to biopsy both hard and fleshy areas of unusual tumors is reviewed.

Fatal complement-induced leukostasis after diatrizoate injection. Principles of clinicopathologic diagnosis.

A case of fatal radiographic contrast medium (RCM)-induced pulmonary granulocyte aggregation (leukostasis) showed massive elevation of the postmortem histamine level. Suspicion of this phenomenon in diverse clinical settings permits clinical and pathological documentation via increased plasma levels of C3a and other means. The existence of effective prophylaxis stimulates a search for predictive tests.