[Nerve and deep vein compression by femoral artery pseudoaneurysm in a patient with multiple exostosis]. / Compression nerveuse et veineuse profonde par un faux anévrysme de l'artère fémorale superficielle au cours d'une exostose multiple.

The multiple exostosis is a hereditary bone tumour. Generally, its complications are benign and are related to compressing surrounding structures such as nerves and vessels. This is the case of a 52-year-old woman with a family history of multiple exostosis, which was complicated by a pseudoaneurysm of the right superficial femoral artery. The delay in diagnosis was allowed to develop this pseudoaneurysm which caused nervous and deep venous compression.

Autoclaved cercarial vaccine against schistosomiasis: ultrastructural and biochemical studies.

Autoclaved cercarial vaccine (ACV) was found to be highly effective in eliciting protective immunity against experimental Schistosomal mansoni. So, the aim of this study was to analyse ACV biochemically and to study ultrastructural changes inflicted on the cercariae as a result of autoclaving, thus rendering it highly protective. Results of this study showed that approximately 100 microg protein and 44 microg carbohydrate were obtained from 10(3) cercariae. The predominant sugar was fucose. Galactose, glucose, manose, galactosamine and glucosamine were also detected. Threonine, glycine, serine and glutamic acid comprised approximately 53.7% of the amino acid residues of the protein. Ultrastructural study revealed preserved architecture of the cercariae. The tails were still attached to the posterior ends of the bodies. However, in others the tails were separated from the bodies and appear schistosomula like. There were also some morphological changes such as thinning of the pericortical envelop with appearance of surface pores.

The durability of external beam radiation therapy for prostate cancer: can it be identified?

PURPOSE: We establish criteria to identify a durable response to external beam radiation therapy by calculation of biochemical progression-free probability for patients who attained and maintained defined nadir prostate specific antigen (PSA) levels more than 5 years after treatment. MATERIALS AND METHODS: A total of 460 patients were treated with external beam radiation monotherapy from 1976 to 1995. Patients with PSA less than 0.5 (group 1) or 0.5 to 1.0 (group 2) ng./ml. more than 5 years after treatment were identified. Treatment failure was defined as 3 consecutive increases in PSA after nadir. Progression-free probability after 60 months was calculated for each group. A comparison was also made to patients achieving the same nadir levels anytime after treatment. RESULTS: Failure occurred at 133 months in 1 of 26 group 1 patients (4%) and at a median of 76 months in 5 of 26 group 2 patients (19%). At 10 years progression-free probability was 91% for group 1 compared to 72% for group 2 (p = 0.0575). These same nadir levels anytime after treatment were associated with higher failure rates of 55% for group 1 and 72% for group 2. CONCLUSIONS: If a PSA nadir of less than 0.5 ng./ml. was maintained 5 years after therapy, subsequent failure was rare. Although statistical significance was not reached (p = 0.0575), a higher failure rate was noted if the nadir PSA was 0.5 to 1.0 ng./ml. at 5 years. Thus, patients with PSA 0.5 to 1.0 ng./ml. require careful continued surveillance. Nadir levels less than 1.0 ng./ml. anytime before 5 years were associated with a substantial risk of subsequent progression.

Does CagA contribute to ulcer pathogenesis in a developing country, such as Sudan?

BACKGROUND AND OBJECTIVE: In Western populations, peptic ulcer disease is closely associated with Helicobacter pylori (H. pylori) strains expressing the CagA antigen. In Africa the prevalence of H. pylori infection and peptic ulcer disease is high, although information regarding potential virulence factors is lacking. This study examines the prevalence of antibodies to CagA both in African patients with dyspepsia who are undergoing gastroscopy, and in asymptomatic healthy African volunteers. METHODS: Eighty two consecutive patients (median age 34 years, range 15-73 years), attending for gastroscopy were studied, of whom 78 (95.1%) were subsequently found to be Helicobacter positive. Three antral biopsies were obtained from each patient and 5 ml of blood was taken for determination of CagA seropositivity using western blot analysis. CagA seropositivity was also determined in 65 H. pylori positive healthy volunteers (median age 30 years, range 18-70 years), with no symptoms or previous history of gastroduodenal disease. RESULTS: Of the 78 H. pylori positive patients, CagA seropositivity was present in all 22 patients with active peptic ulcer disease (100%), in eight of nine patients with duodenitis (89%), in 15 of 19 patients with macroscopic gastritis (78.9%), and in 24 of 28 patients with a normal endoscopy (85.7%). On histological assessment, 46 patients had chronic active gastritis, 29 patients had gastritis with atrophy and three patients had intestinal metaplasia. CagA seropositivity rates were 84.7%, 93% and 100%, respectively, for these groups. In the 89 healthy volunteers studied, 57 of the 65 H. pylori positive subjects (87.7%) were seropositive for the CagA protein. CONCLUSIONS: As in Western countries, CagA seropositivity in this African population was closely related to endoscopic gastroduodenal disease, and to the presence of more advanced histological lesions in the antrum. However, there was also a high prevalence of CagA seropositivity in asymptomatic healthy individuals, suggesting that factors other than CagA predominate in ulcer pathogenesis in this population.

PSA for outcome prediction and posttreatment evaluation following radiation for prostate cancer: do we know how to use it?

Pretreatment prostate-specific antigen (PSA) has been shown to be a powerful predictor of expected outcome after radiation for prostate cancer. Additional measures such as recursive partitioning analysis and PSA Cancer Volume calculations are further refining this useful tool to provide the greatest degree of prognostic information. The post-treatment PSA level is also being used as a means to assess therapeutic efficacy rapidly and objectively. Although no single PSA value has been shown to equate to long-term clinical tumor control consistently, consensus has been reached regarding the value of a rising PSA level as an early surrogate for tumor recurrence. Since the first introduction of PSA as a tumor marker, we have become much more comfortable with what it means, the ways it can help us, and how to use it.

High dose rate vaginal brachytherapy in early stage endometrial carcinoma: preliminary analysis.

From 1987 to 1993, 69 women diagnosed with FIGO stages I and II carcinoma of the endometrium underwent postoperative adjuvant irradiation (RT) under protocol with high dose rate (HDR) afterloading vaginal apex brachytherapy. All patients initially underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy. Forty-four women received HDR brachytherapy alone and 25 received external beam RT as well as HDR brachytherapy. The median follow-up was 45 months. The 5-year disease-free survival was 92% and the overall survival rate was 79%. Multivariate Cox regression analysis revealed that grade, age, and stage were significant predictors of survival. The overall acute and late side effects were minimal. It appears that HDR vaginal brachytherapy is prevention of vaginal recurrence in endometrial carcinoma and should be considered an effective treatment option.

Prostate-specific antigen after radiation therapy. Prognosis by pretreatment level and post-treatment nadir.

After external beam radiation therapy, pretreatment prostate-specific antigen (PSA) is the most powerful predictor of outcome as measured PSA (biochemical) failure. The post-treatment nadir levels of PSA that predict best for subsequent freedom from PSA failure are debatable, and many nadir levels have been proposed as targets. Although lower nadirs generally are associated with superior outcomes, the identification of a single absolute nadir level was not selected at a recent ASTRO consensus conference. Rather, three consecutive PSA rises above the nadir, with date of failure at the midpoint between the nadir and first rise, were selected as a more useful end point for treatment failure.

Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation.

PURPOSE: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. METHODS AND MATERIALS: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. RESULTS: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p=0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. CONCLUSION: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas.

Breast cancer during pregnancy: quantifying the risk of treatment delay.

OBJECTIVE: To quantify the risk of axillary nodal metastases due to delayed treatment of breast cancer during pregnancy. METHODS: A mathematical model using recently published data was developed to correlate primary breast tumor size with the percentage of pathologically positive axillary lymph nodes. Using this relationship obtained from pathologic data and the accepted relationship of tumor growth and time, Y2 = Y1e(In2)n/DT, an equation estimating the increased risk of axillary metastases due to each day of treatment delay was derived: delta X = 3.7 n/DT, where X = percent positive axillary lymph nodes, n = number of days delay in treatment, and DT = tumor doubling time. RESULTS: A 1-month delay in treatment for an early-stage primary breast cancer with a 130-day doubling time increases the risk of axillary lymph node involvement by 0.9%. A 3-month delay increases the risk by 2.6%, and a 6-month delay by 5.1%. For breast cancer with a 65-day doubling time, a 1-month delay increases the risk by 1.8%, a 3-month delay by 5.2%, and a 6-month delay by 10.2%. CONCLUSION: Axillary lymph nodes are the most important prognostic indicator for survival in breast cancer. Our mathematical model suggests the daily increased risk of axillary metastases due to treatment delay is 0.028% for tumors with moderate doubling times of 130 days and 0.057% for tumors with rapid doubling times of 65 days. This minimal maternal risk may be acceptable to some third-trimester pregnant women with early breast cancer, who prefer organ-sparing treatment with radiation after delivery to a mastectomy during pregnancy. This model further quantitates the increased risk of mortality borne by pregnant women whose breast cancer diagnosis is delayed.

Pulmonary metastases from prostate cancer.

BACKGROUND: Lung metastases are rarely a significant factor in the management of prostate cancer. The usual pattern of spread is via lymphatic pathways, with pulmonary metastases virtually always occurring with osseous metastases. Previous reports suggest that androgen deprivation often fails to produce significant improvement in patients with pulmonary metastases; however, in the authors' experience, it has been successful in achieving objective responses. METHODS: A retrospective review of a large prostate cancer data base was performed to identify patients with adenocarcinoma of the prostate and radiographic evidence of pulmonary metastases. A unique case of isolated pulmonary metastases with exsanguinating hemoptysis is described to illustrate the dramatic response to androgen deprivation. RESULTS: Of 1290 patients with biopsy-proven adenocarcinoma of the prostate, in 47 (3.6%) patients radiologic evidence of pulmonary metastases was observed. Twenty-six (2.0%) patients demonstrated pulmonary metastases at the time of initial detection of metastatic disease. The radiographic appearance of pulmonary metastases was consistent with lymphangitic spread in the majority of patients. Of patients who received no hormonal therapy before the development of pulmonary metastases, 76.5% showed improvement in the appearance of their pulmonary lesions with androgen deprivation. As expected, survival was longer for those patients presenting with hormone-naive disease and pulmonary metastases than for patients with hormone-refractory disease and pulmonary metastases. The difference in survival, however, was not statistically significant. CONCLUSIONS: Pulmonary metastases are not encountered commonly in patients with prostate cancer. Androgen deprivation remains the most effective treatment and, among hormone-naive patients, objective response is common. The prognosis for patients with hormone-naive disease and pulmonary metastases is not necessarily worse than for patients with metastatic disease at other sites.

Prostate-specific antigen for pretreatment prediction and posttreatment evaluation of outcome after definitive irradiation for prostate cancer.

PURPOSE: This study was undertaken to assess the predictive value of pretreatment prostate-specific antigen (PSA) and the difference between clinical and PSA disease-free status in patients with long-term follow-up after irradiation for prostatic carcinoma. Comparison of the distribution of prognostic factors between surgical and radiation series was also made. METHODS AND MATERIALS: From 1975-1989, 652 patients with clinical Stage A2-C prostatic adenocarcinoma were definitively irradiated using external beam therapy. One hundred and fifty patients with banked serum and up to 14 years follow-up have pretreatment PSA levels and 355 patients with up to 17 years follow-up have posttreatment values. Treatment failure was analyzed by tumor stage, grade, and four pretreatment PSA categories. Disease-progression was evaluated by clinical and biochemical (PSA) endpoints. Prognostic factors were compared to two surgical series. RESULTS: A significant difference was seen in clinical and PSA disease-free (PSA < or = 4.0 ng/ml) status based on tumor grade, stage, and pretreatment PSA category. Although the expected clinical outcome has been well-documented previously, results based on posttreatment PSA levels show 5-year disease-free survivals reduced by 10-16% and 10-year survivals lessened by 15-39% depending upon the particular tumor grade and stage. The earlier stage, lower grade tumors showed the largest difference between clinical and biochemical recurrence rates at the longest interval from treatment. Even more notable were the differences in the clinical and PSA disease-free rates based on the pretreatment PSA level. Comparing the irradiated patients to two surgical series showed that the former had a larger percentage of more advanced stage tumors with more unfavorable PSA levels as compared to prostatectomy patients. CONCLUSION: With long-term follow-up, the pretreatment PSA level continues to be a powerful predictor of clinical and biochemical outcome in patients irradiated for apparently localized prostate cancer. Differences between clinical and PSA outcome can be considerable, but oftentimes clinically insignificant. The distribution of prognostic factors between radiation and prostatectomy series seems to favor the latter.

Potential benefit of improved local tumor control in patients with prostate carcinoma.

BACKGROUND: In the case of prostate carcinoma, radiation therapy is a locally applied treatment modality in a malignancy known for systemic dissemination. Because significant efforts and resources currently are being consumed to improve local tumor control, failure patterns and potential curative gain deserve appropriate assessment. METHODS: From 1975-1989, 647 patients with clinically localized prostate carcinoma were definitively irradiated for biopsy-proven adenocarcinoma of the prostate. Failure patterns were examined, and survival advantage based on improvement in either local or distant disease control was calculated. Distant metastatic rate and cause-specific survival analyses were used as parameters by which to compare the outcome for patients in whom local tumor control was achieved with patients who experienced local failure, thereby assessing further the importance of the effectiveness of locally applied therapy. RESULTS: Three hundred ninety-two (61%) patients at the time of this writing were clinically disease free. Sixty-two (10%) patients failed locally only, 133 (20%) distantly only, and 60 (9%) developed local and distant recurrent disease. Both local and distant failure rates were higher in patients with more advanced stage lesions at presentation, and distant failure rates significantly increased in patients with less differentiated tumors. Pretreatment prostate-specific antigen was found to be useful in predicting recurrence patterns. Overall, there appeared to be more potential for improvement in survival secondary to reducing distant metastasis. The distant survival advantage (DSA) of reducing distant metastases, compared with the local survival advantage (LSA) of improving local tumor control, was 26 versus 14%. Although DSA was greater than LSA within each stage category, the potential to improve survival was most significant in the Stage C group, where DSA was 35% and LSA 16%. Although LSA varied little according to tumor grade, DSA was dependent on tumor grade and varied from 13% for well differentiated lesions to 38% for poorly differentiated lesions. Distant failure free survival at 10 years was 63% for patients with local control and 45% for those with local failure (P = 0.01). Similarly, 10-year cause-specific survival was 75% in locally controlled patients compared with 48% for those with local recurrence (P < 0.001). CONCLUSIONS: Although better local tumor control should translate into at least modest survival gain for patients with prostate carcinoma, additional advantage may be seen with improved systemic therapy or perhaps earlier diagnosis to reduce further the distant metastasis rate.

Carcinoma of the prostate: race as a prognostic indicator in definitive radiation therapy.

PURPOSE: To characterize the racial differences in prognostic factors and treatment outcome for patients undergoing radiation therapy for carcinoma of the prostate. MATERIALS AND METHODS: From January 1975 through December 1989, 489 white and 157 black men with carcinoma of the prostate underwent irradiation. Factors analyzed were patient age, tumor stage and grade, prostate-specific antigen (PSA) levels, and disease-control and survival rates. RESULTS: More black patients than white patients were found to have poorly differentiated tumors. Black patients had higher PSA levels before and after treatment, resulting in a higher distant failure rate and poorer overall, cause-specific, and disease-free survival rates. CONCLUSION: Black men have more aggressive prostatic tumors, a higher rate of metastasis, and a poorer survival rate than do white men.

Nuclear morphometry as a predictor of response to neoadjuvant chemotherapy plus radiotherapy in locally advanced cervical cancer.

We have studied nuclear morphometric characteristics from H & E slides of 23 patients with locally advanced squamous cell carcinoma of the cervix treated with neoadjuvant chemotherapy (cis-platinum + 5-fluorouracil) plus radiation therapy to see if a correlation existed between these morphometric assessments and response to chemotherapy/radiotherapy. On the same 23 patients, biopsies were taken at three times: before treatment, after chemotherapy alone, and after chemotherapy plus radiation therapy. Using the Zeiss Videoplan III morphometric workstation, tumor nuclear area and nuclear roundness factor were assessed on three different tumor cell populations: the basal, intermediate, and superficial cell layers. There were two principal results from this study: (1) There was a significant (P = 0.007) reduction in the appearance of the basal layer of tumor cells following chemotherapy. (2) The reduction in nuclear area of intermediate layer tumor cells by chemotherapy alone was significant in responders (P = 0.005) but not in nonresponders (P = 0.74) to the combined therapy. The ability to differentiate between responders and nonresponders to combined therapy after only the chemotherapy has been administered may allow more rational patient selection for radiation therapy.

Treatment of clinical local failure after radiation therapy for prostate carcinoma.

From a base population of 634 patients with prostate cancer treated by external beam therapy with a median followup of 8 years and 123 patients treated by interstitial brachytherapy with 125iodine (125I) isotope with a median followup of 13 years, those with local failure only were identified. There were 57 external beam radiotherapy (9%) and 15 125I (12%) treated patients with local failure only among the base population. All but 3 patients (2 given external beam radiotherapy and 1 given 125I) were treated with hormonal manipulation without extirpative surgery. The overall cancer-specific median survival with hormonal therapy from the date of local failure was 70 months for 55 patients treated by external beam radiotherapy and 87 months for 14 treated by 125I. Patients with low grade, small volume tumors most likely to benefit from salvage surgery are also those who will experience prolonged survival with hormonal therapy. Patients with local failure only treated by hormonal manipulation had statistically longer cancer-specific survival rates from the date of failure than did similarly treated patients experiencing distant failure with local failure. This finding suggests a difference in the biological aggressiveness between tumors associated with distant and local failure versus local failure only. To select the patients with local failure only who would be candidates for the potentially benefited by salvage surgery, those with pretreatment stage A or B disease who were less than 72 years old were identified. A total of 17 patients treated by external beam radiotherapy and 7 treated by 125I fulfilled these criteria. Therefore, as determined by local failure only, patient age and pre-radiation clinical stage, only 2 to 5% of the patients treated with radiation modalities are ultimately optimal candidates for salvage surgery.

Prostate-specific antigen to determine progression-free survival after radiation therapy for localized carcinoma of prostate.

Prostate-specific antigen (PSA) levels after radiation therapy will more precisely and objectively identify the presence of persistent prostate carcinoma. We determined the impact of PSA marker levels on progression-free status for 123 patients treated by interstitial implantation (I-125) and 311 patients treated by external beam therapy (XRT) who have been followed for a median of 109 and 51 months, respectively. Actuarial progression-free survival curves were calculated, using standard clinical criteria, and then recalculated, using PSA marker criteria. Sera obtained twelve months or more after the initiation of XRT and twenty-four months or more after the date of I-125 were used for determination of PSA levels. Using normal PSA level (by Hybritech assay < or = 4.0 ng/mL) as the criterion for progression-free status for patients treated by XRT, 35 percent of patients with Stage A2, 20 percent of patients with Stage B1 or B2, and 10 percent of patients with Stage C tumor were progression-free at ten years. The progression-free survival by clinical criteria for Stage A2 and 65 percent, B1 was 40 percent, B2 was 35 percent, and C was 25 percent. Using undetectable PSA level (< or = 0.5 ng/mL) as the criterion, less than 10 percent of patients were progression-free at ten years, regardless of stage, grade; and treatment modality. This information should not be interpreted as indicating that radiation is ineffective therapy for prostate cancer, since clinical control of the disease among men in their eighth decade is a more practical goal than marker control. However, PSA monitoring after radiation therapy and after any local therapy for prostate cancer will provide more precise information on the success of that therapy in ablating disease.

Reevaluation of prostate biopsy after definitive radiation therapy.

We have previously reported (1987) that a positive biopsy from a clinically normal prostate eighteen months or more after interstitial Iodine 125 or external beam irradiation predicted disease progression. In the present study, all biopsies were reexamined by the same pathologist (LEL) and correlated with long-term patient status. Of twenty-six positive biopsy specimens, twenty-two were reconfirmed as positive and four were reassigned to a negative diagnosis (false positive = 15%). Seventy-two of seventy-seven negative specimens were available for reexamination and seventy were reconfirmed as negative while two were reassigned to a positive diagnosis (false negative = 2%). A statistically higher incidence of local and/or distant failure for patients with positive biopsy specimens compared with patients with negative biopsy specimens was again confirmed (p = < 0.001). However, there is a group of patients with a positive biopsy (17%) who remain clinically free of disease at greater than ten years of follow-up. Therefore, a positive biopsy is not an absolute indication of imminent failure. Our results demonstrate the technical difficulty and potential error in interpreting prostate biopsies after radiation therapy. Therapeutic decisions should be based not only on biopsy histology but must also weigh the patient's initial tumor stage and grade, current clinical examination, PSA level, age, and health.

Prognostic significance of post-irradiation prostate biopsies.

Over the last 2 decades, the prognostic significance of post-irradiation prostate biopsy has been debated. Studies with long-term follow-up have shown a predictive effect with regard to local tumor failure and disease-free survival. More recently collected data involve the use of prostate ultrasound and prostate-specific antigen; the latter appears to be a good prognostic indicator on its own. Currently, the practical usefulness of post-treatment biopsy for clinically undetectable disease remains undefined, since definitive therapy for positive findings cannot be widely applied, carries significant morbidity, and, as yet, is of questionable benefit. Further study is certainly necessary, and it is perhaps under these conditions that this post-therapy procedure should be used.

Flow cytometric DNA content and clinical outcome in patients with non-small cell lung cancer given postoperative radiation therapy.

DNA content by flow cytometry was assessed in 47 cases from a series of 130 patients with non-small cell lung carcinoma (NSCLC) given radiation therapy postoperatively. This was done in an attempt to identify which patients might benefit, or not benefit, from postoperative radiotherapy. From archival formalin-fixed paraffin-embedded specimens, 16 of the 47 cases (34%) had DNA diploid tumors while 31 cases (66%) were nondiploid. A diploid DNA content was significantly related to improved overall survival (P = 0.0061) and tumor-free survival (P = 0.0167) but not with frequency of tumor recurrence within the irradiated field. Histological grade was not significantly related to overall survival, tumor-free survival, or frequency of in-field tumor recurrence. DNA content was found in this study of NSCLC patients irradiated postoperatively to be a useful marker for predicting survival but not for predicting local recurrence.