Local approaches to hereditary breast cancer.

The diagnostic and local treatment modalities of hereditary breast cancer (HBC) are evolving based on emerging evidence from new imaging, radiotherapy and surgical studies. The optimal selection of diagnostic and therapeutic strategies for the individual HBC patient remains an area of active research in this relatively new patient population. In this context, some rational pathways of intervention are currently available to both reduce cancer risk in mutation carriers without a cancer diagnosis, as well as to reduce the risk of recurrence or new cancers among the carriers already diagnosed with a malignancy. It is encouraging to notice to what degree certain interventions have successfully reduced both the risk of malignancy and the anxiety associated with this genetic diagnosis. This updated report aims at summarizing the most recent findings, while it identifies the areas of uncertainty that remain, and continue to present difficult challenges, particularly among younger HBC patients.

Hereditary breast cancer: clinical features and risk reduction strategies.

Risk-reduction interventions for BRCA-related breast cancer are relevant not only for clinical decisions in breast cancer patients but also for healthy subjects who are potential candidates to undergo similar interventions. The literature on the impact of different surgical options and adjuvant systemic approaches aimed towards risk reduction for ipsilateral and contralateral breast cancer recurrences is briefly reviewed. Breast-conserving surgery is associated with a higher probability of local recurrence, but is counterbalanced by effectiveness of chemotherapy in reducing this risk. Consistent support for the hypothesis that antiestrogens are effective in reducing contralateral breast cancer risks is available from the literature. On the other hand, data on chemoprevention approaches for healthy subjects are too preliminary to draw any conclusions. Studies including conventional and newer hormonal drugs are needed to demonstrate the benefit of chemoprevention approaches. These may also deepen our knowledge on possible differences in the likelihood of clinical benefit to be expected among BRCA1- and BRCA2-altered tumours.

Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer.

Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t)), perfusion fraction (f(p)), and pseudodiffusivity (D(p)). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (±standard deviation) values (2.44 ± 0.30 vs. 1.34 ± 0.39 µm(2)/msec, P < 0.01) and D(t) (2.36 ± 0.38 vs. 1.15 ± 0.35 µm(2)/msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 ± 5.0% vs. 6.9 ± 2.9%, P = 0.06), but less so with D(t) (1.14 ± 0.32 µm(2)/msec vs. 1.18 ± 0.52 µm(2)/msec, P = 0.88) and D(p) (14.9 ± 11.4 µm(2)/msec vs. 16.1 ± 5.7 µm(2)/msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors.

Black aspergilli and ochratoxin A in grapes in Italy.

The objective of this research was to investigate the presence of black aspergilli in grapes grown in Italy and to study the effect of environmental and cultural factors able to influence fungal incidence and ochratoxin A (OTA) presence. In this 3-year study, black aspergilli were frequently associated with grape berries; they were present in bunches starting from setting, colonising most berries at early veraison. Aspergillus carbonarius was never dominant at the different growth stages, or in different geographic areas and years, but it was confirmed as the key fungus because of the high percentage of strong OTA producer isolates in the population. The number of OTA producer strains, isolated in each vineyard at the different growth stages, was generally very limited and they were never statistically correlated to OTA content in bunches. The effect of geographic area on fungal flora was confirmed by statistical analysis, even though a major role was played by meteorological conditions, both on fungal colonisation and OTA content in bunches. Discriminant analysis gave promising perspectives for predicting OTA presence in vineyards in the future, based on summation of degree-day and rain in the period between 21st of August and 10th of September.

Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.

Expression of metastases-associated genes in cervical cancers resected in the proliferative and secretory phases of the menstrual cycle.

Previous retrospective studies suggest that the phase of the menstrual cycle at surgery (proliferative versus secretory) for breast cancer may significantly affect patient survival. Fluctuations during the menstrual cycle of the expression of genes involved in metastases in breast cancer tissue have also been reported. We hypothesized that the menstrual phase may also affect similar changes in gene expression of other cancers. We focused our attention on cancer of the uterine cervix because the hysterectomy specimen obtained at original surgery for the cancer can be used retrospectively to determine cycle phase. We analyzed tumor specimens from 36 premenopausal cervical cancer patients who had undergone hysterectomy as their primary treatment. We used reverse transcription-PCR to quantify gene expression during the different phases of the menstrual cycle as determined from the endometrial specimen. We explored a panel of genes that may affect metastatic propensity, namely, metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2), cyclooxygenase 1 and 2 (COX-1 and COX-2), and vascular endothelial growth factor (VEGF). A significantly higher level of TIMP-2 and COX-2 gene expression (P = 0.007 and 0.030, respectively) was detected during the proliferative phase compared to the secretory phase of the cycle. The expression of the other genes was not significantly affected by the stage of the menstrual cycle. The finding that TIMP-2 and COX-2 expression in cervical cancer may be affected by the stage of the menstrual cycle supports the hypothesis that ovarian hormones may affect the expression of genes involved in metastasis. These findings need to be replicated, and their implications for tumor angiogenesis, invasion, and metastatic propensity need to be explored both in human studies and in experimental models.

Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy.

PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel therapy and if they correlate with response to treatment. EXPERIMENTAL DESIGN: Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients. RESULTS: Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the tumor cell apoptotic response to the first dose of paclitaxel. CONCLUSIONS: These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment.

Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: implications for early prediction of breast cancer response to neoadjuvant treatment.

The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer.

Concurrent paclitaxel and radiation therapy for breast cancer.

Few studies have evaluated the role of concurrent chemoradiation therapy in the management of locally advanced breast cancer. The availability of radiosensitizing chemotherapeutic agents that are effective in breast cancer and the encouraging results achieved by concurrent chemoradiation in other malignancies have prompted us to investigate this approach. Paclitaxel is a promising agent for use with concurrent radiotherapy because of its single-agent efficacy profile and its radiosensitizing effects. A clinical protocol of preoperative paclitaxel and radiation in locally advanced breast cancer is ongoing at our institution to test feasibility, measure pathologic response at mastectomy, and explore association of pathologic response with molecular tumor markers. Initially, the study was designed to test weekly paclitaxel at a dose of 60 mg/m2 during radiation therapy, delivered 5 days a week at 200 cGy fractions to a total dose of 50 Gy over 5 weeks. Due to severe skin toxicity in the first two patients, the protocol was amended to change the scheduling of paclitaxel to 30 mg/m2 twice weekly and to reduce the radiation to 180 cGy fractions to a total dose of 45 Gy, delivered 5 days a week over 5 weeks. Presently, 13 patients have been accrued; preliminary data indicate good tolerance to twice-weekly paclitaxel, and four of eight evaluable patients have achieved pathologic response (one patient who received the weekly regimen and three who received the twice-weekly regimen). In addition, sequential fine-needle aspirations of palpable breast cancers were obtained in patients enrolled in a parallel study of preoperative single-agent paclitaxel (200 mg/m2 every 2 weeks, for a total of four cycles before breast surgery). Preliminary results suggest that a steep increase in the mitotic index occurs during the first day after paclitaxel administration and plateaus between the second and the third day, then decreases to pretreatment values. The peak apoptotic index occurs at approximately 72 hours after paclitaxel administration and decreases at approximately 98 hours. These initial findings suggest that twice-weekly dosing of paclitaxel may optimize recruitment of cells into the G2/M phase of the cell cycle, the most radiosensitive phase.

Radiosensitivity of Koch ileal reservoir.

PURPOSE: To acquire preliminary information on the radiosensitivity of the Koch ileal reservoir by reviewing acute and late toxicity incurred by nine patients who received pelvic radiotherapy after cystoprostatectomy with lower urinary reconstruction utilizing a Koch ileal reservoir with bilateral uretero-ileal-urethrostomy. METHODS AND MATERIALS: All patients were irradiated because of synchronous locally advanced prostate cancer (pT3). A fourfield box technique at 100 cm source-axis-distance (SAD) with all fields treated every day at 1.8 Gy daily fractions, to a total dose of 45-50.40 Gy was used. The average AP portal dimension was 11 x 11 cm, and the average lateral was 7 x 8 cm. All portals were shaped using custom shields to optimize protection of normal tissues not suspected of tumor involvement (small bowel, posterior rectal wall). No attempt was made to shield the Koch ileal reservoir. For each patient, comparison of the treatment portals with the Kochgram radiography (gravity cystogram) confirmed the inclusion of the majority of the Koch ileal reservoir within the radiation fields. Acute and late morbidity was measured by RTOG toxicity criteria by retrospectively reviewing the patients' records. RESULTS: Only mild acute toxicity was reported by the patients: Six patients experienced grade 1 acute urinary toxicity and one suffered Grade 2 acute urinary toxicity. In four patients Grade 1 acute gastrointestinal toxicity occurred and in two patients Grade 2 toxicity occurred. With a median follow-up of 50 months late toxicity consisted mainly of microscopic hematuria in six patients and persistent frequency in two patients (with spontaneous improvement respectively at 4 and 6 months after radiation). No patients experienced acute or late Grade 3 or 4 genitourinary or gastrointestinal toxicity. CONCLUSION: The use of moderate doses of pelvic radiotherapy (45-50.40 Gy) at standard fractionation was well tolerated among nine patients who received pelvic radiation for invasive prostate cancer detected at the time of cystectomy and Koch ileal reservoir diversion. These preliminary data support the evidence that patients with a Koch ileal reservoir could safely undergo postoperative pelvic radiotherapy in these dose ranges and fractionation.

Radical prostatectomy and postoperative irradiation in patients with pathological stage C (T3) carcinoma of the prostate.

PURPOSE: Adenocarcinoma of the prostate is the most common human cancer of internal organs. Radical surgery is regarded by many to be the treatment of choice for capsule confined disease. Since accurate preoperative assessment of tumor stage is difficult to define, many patients are subsequently found to have pathological stage C (T3) disease. These patients should be considered for adjuvant radiotherapy. METHODS AND MATERIALS: A group of 201 PS C (T3) unselected patients, treated with radical prostatectomy and limited pelvic lymphadenectomy, received postoperative irradiation to the prostate bed. This radiotherapy was given between 42-90 days after surgery and consisted of a median dose of 48 Gy. Patient survival, disease free survival, time to clinical and chemical relapse and the incidence of local and systemic relapse were analyzed. The influence of multiple parameters on the treatment outcome including patient age, treatment period, clinical stage, pathological stage, Gleason's score, prostate specific antigen (PSA), radiotherapy techniques and radiation dose were examined using univariate and multivariate analysis. Follow-up ranged from 3 to 15 years, with a median of 5 years. RESULTS: The overall 5- and 10-year actuarial survival was 92% and 83% (median > 10 years), respectively and the 5- and 10-year disease-free survival (clinical and PSA) was 67% and 53% (median > 10 years), respectively. A total of 61 (30%) patients had a recurrence, including 23 (11%) patients who had clinical and 38 (19%) who had PSA recurrence. Of the 23 patients with clinical recurrence, 10 (5%) had local recurrence, including two patients who had local and systemic recurrence. Pathological stage and Gleason's score were independently predictive of recurrence (each with p < 0.001 after controlling for the other). Patients in the worst prognostic category with pathological stage C3 and Gleason's score 8-10 were predicted to be at 7.2 times the risk of recurrence, compared to stage C1 or C2 and Gleason's score 2-7 patients. Preoperative PSA level (> 25 ng/ml) was also an important independent factor predicting tumor recurrence, p = 0.05. All other investigated parameters were not significant in predicting tumor recurrence. This treatment program was very well tolerated by the study patients, with seven (3.5%) recorded with major and 18 (9%) with minor surgical complications, while 65% of patients had minor and clinically insignificant radiation complications. CONCLUSION: Surgery followed by moderate dose radiotherapy in patients with PS C (T3) prostatic carcinoma was well tolerated and resulted in excellent overall and disease free survival, with a low incidence of local recurrence. New treatment strategies need to be developed for patients with C3 tumors and those with high (8-10) Gleason's score and those with high (> 25 ng/ml) PSA level at diagnosis.

Abdomino-pelvic hyperthermia and intraperitoneal carboplatin in epithelial ovarian cancer: feasibility, tolerance and pharmacology.

PURPOSE: To investigate the feasibility, toxicity, and pharmacokinetics of intraperitoneal (i.p.) carboplatin (CB) with concomitant abdomino-pelvic hyperthermia (HT) in advanced ovarian cancer patients. METHODS AND MATERIALS: Patients with residual disease mainly confined to the peritoneal cavity after platinum based chemotherapy received an initial course of i.p. CB for baseline pharmacokinetics followed by three cycles of i.p. CB with concomitant regional hyperthermia. The goal of HT was to achieve at least 45 min of intraperitoneal temperature > 42 degrees but < 50 degrees C while maintaining normal tissue temperatures < 43 degrees C and systemic body temperatures < 38 degrees C. No analgesic premedication was used. Thermometry was recorded by multisensor fiberoptic probes placed within the peritoneal cavity, bladder, vagina, and oral cavity. RESULTS: Thirteen patients received a total of 31 sessions. Our intraperitoneal temperature goal could not be achieved because of patient intolerance. At best, we could maintain intraperitoneal temperatures > 40 degrees C, for more than 40 min in 7 of 31 sessions. The average values of thermal variables were T90 = 40 degrees C, TAVE = 41 degrees C, TMIN = 38.2 degrees C, and TMAX = 42.9 degrees C. The mean maximum systemic temperature was 38 degrees C. Acute thermal toxicities requiring early interruption of hyperthermia were systemic temperature exceeding 38 degrees C (11 of 31), abdominal pain or generalized distress (20 of 31), and vomiting (2 of 31). Hematological toxicities were not increased by hyperthermia. Pharmacokinetics were consistent with enhanced clearance of CB by HT. Lower radio frequencies (< 75 MHz) achieved better heat deposition in the peritoneal cavity than higher frequencies (> 75 MHz). Two of the 13 patients (a Stage III and a Stage IV patient) are alive with no evidence of disease at 40 and 43 months from treatment. CONCLUSIONS: Intraperitoneal temperatures in the range of 40 degrees C maintained for approximately 40 min can be achieved within the described setting. The probability of successful induction of therapeutic intraperitoneal temperatures appears to be higher when frequencies below 75 MHz are used. Patients who are potentially platinum sensitive and have minimal residual disease could potentially benefit from the combined treatment under the conditions studied. However, this temperature-time range appears inadequate against platinum resistant disease, and/or bulky residual pelvic disease. Alternative approaches such as whole body hyperthermia and carboplatin are warranted to overcome some of the obstacles observed.

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy.

PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.

Surgical therapy and radiotherapy for carcinoma of the esophagus. Treatment results in 195 patients.

Between 1963 and 1986, 195 patients with carcinoma of the esophagus were seen in the Department of Radiation Oncology at the University of Southern California School of Medicine. Of these 195 patients, 137 had unresectable or inoperable tumors and received radiotherapy. A combination of radiotherapy and surgical therapy was used in 46 patients, 9 patients were treated with surgery alone, and three with chemotherapy alone. Among the nonsurgical patients, 13 scored less than 50 on the Karnofsky scale, 25 had distant metastases, and 69 lost more than 10% of their body weight. The majority (94%) had squamous cell carcinoma and a few (6%) had adenocarcinoma. Fifty percent had middle esophageal lesions, 30% had lower lesions, and 20% had upper esophageal lesions. Stage I was diagnosed in 13%, II in 27%, III in 29%, and IV in 27%; the disease was not staged in 5%. The 5-year actuarial survival rate for all patients was 4% (median 32 weeks). The 5-year survival rate of the 46 patients with combination therapy was 18%, and it was 2% for the remaining 149 patients (p less than 0.001). These figures are independent of stage of disease. The 2-year survival rate by stage was as follows: I, 25%; II, 21%; III, 5%; and IV, 0% (p less than 0.001). Complete response was obtained in 18% and partial response in 41%. Complete response was dependent on the tumor stage. It was 40% for stage I disease, 23% for stage II, 11% for stage III, and 6% for stage IV disease. Similarly, a larger percentage (39%) of the 46 patients with combination surgical/radiation therapy had a complete response than of patients treated by either radiotherapy alone (n = 137, 12%) or surgery alone (n = 9, 11%). Complete response and initial performance status were important factors influencing survival (p less than 0.001). Surgery with adjuvant irradiation offered a better survival rate than radiotherapy or surgery used as single modalities. Treatment results for patients with advanced carcinoma of the esophagus remain poor.

Immunophenotypic analysis of peripheral blood leukocytes at different stages of HIV infection. An analysis of asymptomatic, ARC, and AIDS populations.

Blood leukocytes from 51 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related syndrome (ARC) were immunophenotyped with the use of monoclonal antibodies and flow cytometry. The patients were placed into four clinically defined groups: HIV-positive asymptomatic (HIV+/A, 8); persistent generalized adenopathy (14); Kaposi's sarcoma (12); and opportunistic infections (17). Immunophenotypes were compared between groups. Statistically significant differences were seen in absolute lymphocyte counts, total T-cells, helper/inducer T-cells, the helper inducer subset of CD4+ lymphocytes, the suppressor inducer subset of CD4+ lymphocytes, activated helper T-cells, and natural killer cells. CD8+ cells and subsets were not statistically different between groups, possibly obscured by large ranges, but median values suggested differences. Results indicate a pattern of increasing or decreasing numbers of certain subpopulations as HIV infection progresses.

An update on radiation therapy in breast cancer.

Radiation therapy plays an important role in the management of both invasive and noninvasive breast cancer. During the last 20 years, the availability of radiation therapy has made it possible to test the feasibility and safety of breast preservation after the diagnosis of early-stage breast cancer. This article summarizes some of the ongoing controversies concerning the use of radiation therapy in the multidisciplinary management of breast cancer.

Application of radiosurgery principles to a target in the breast: a dosimetric study.

PURPOSE: To investigate the technical and physical feasibility of using a radiosurgery-like technique to irradiate a small target within the breast with a single fraction. MATERIAL AND METHODS: During diagnostic biopsy, a tantalum surgical clip is placed in the lesion identified at mammography. Transverse CT scans over the entire breast are obtained, as the patient lies prone on a special table that allows the breast to hang down. The clip is used as a reference point to define the isocenter of the radiation treatment. RESULTS: The clip is visible on port films taken with a 4 MV beam, allowing the isocenter to be set to its planned location. No movement of the hanging breast is visually detected. The possible beam directions are enclosed by a 220 degrees horizontal x 180 degrees vertical angular interval. Dosimetry of two "radiosurgical" examples, (A) seven fixed horizontal beams and (B) six 45 degrees arcs and a 90 degrees sagittal arc using a 4 MV x-ray beam with a 32 mm diameter collimator, are discussed. Both field arrangements produce adequate tumor coverage: the minimum target dose is 83% of the dose maximum in the fixed beam arrangement and 86% in the multiarc setup. In arrangement A the lung and other tissues external to the breast receive dose only from scattered radiation. In arrangement B the maximum lung dose is less than 5% of the dose to isocenter. CONCLUSION: From a dosimetric point of view both described techniques are feasible, and the radiosurgery-like treatment is executable.

High Rate of Positive Anti-Tissue Transglutaminase Antibodies in Chronic Liver Disease.

BACKGROUND: Since the recognition of tissue transglutaminase (tTG) as the target antigen of anti-endomysium antibodies, several ELISA assays using either guinea pig or human recombinant tTG have been developed. The aim of the study was to compare the behaviour of anti-tTG and anti-endomysium antibodies assays in coeliacs and in patients with chronic liver disease. METHODS: 34 patients (24 women, 34.9 ± 12.5 years) with coeliac disease and 41 with chronic liver disease (14 women, 57 ± 11.2 years), including 19 cirrhotics, were evaluated for anti-endomysium antibodies by indirect immunofluorescence and for anti-tTG IgA antibodies by ELISA, using guinea pig liver or human recombinant transglutaminase. RESULTS: The prevalences of anti-tTG and anti-endomysium antibodies were 100% in patients with coeliac disease at diagnosis, 75% and 64.3% in patients on a gluten-free diet. All liver disease patients were negative for anti-endomysium antibodies, while 11 (26.8%) were positive for anti-tTG. All these patients had liver cirrhosis and represented 57.9% of all cirrhotics. The presence of anti-tTG was associated with higher Child-Pugh scores. The use of human transglutaminase determined a reduction in the rate of positive results; however, the rate of positive anti-tTG was still 17.1% in all liver disease patients and 31.6% in cirrhotics. CONCLUSIONS: Our data confirm that anti-tTG have a similar sensitivity compared with anti-endomysium antibodies assay in coeliacs. However, a high prevalence of positive anti-tTG results is observed in cirrhotic patients, even when human recombinant tTG is used. The high prevalence of positive results among cirrhotic patients is associated with more advanced liver disease.

Initial manifestation of acquired immunodeficiency syndrome in the head and neck region.

Initial manifestation of AIDS in the head and neck region occurs frequently. The purpose of this report has been to alert the head and neck surgeon to the occurrence of AIDS-related lesions, their clinical characteristics, and disease outcome. Incomplete recognition of these disorders may delay appropriate diagnostic study and initiation of therapy. We have described 10 patients in whom the initial manifestation of AIDS-related malignancies occurred in the head and neck region. Six of these patients were found to have Kaposi's sarcoma, whereas four had non-Hodgkin's lymphomas. The specific clinical and pathologic aspects of the disease have been described, which represent common patterns of presentation. It is crucial to obtain an accurate social history, as well as a complete medical history from any patient suspected of having AIDS, and prompt biopsy of suspect lesions should be performed.

Increased radiosensitivity of normal tissue fibroblasts in patients with acquired immunodeficiency syndrome (AIDS) and with Kaposi's sarcoma.

Fibroblasts cultured from skin biopsies of patients with AIDS and Kaposi's sarcoma were found to be more radiosensitive than fibroblasts from non-HIV-infected-sources. This supports clinical observations of overt sensitivity to radiotherapy in some AIDS patients with Kaposi's sarcoma.