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[Influence of radiotherapy on lymphocyte subpopulations].

The authors investigated the effects of radiation therapy on the immune system by studying lymphocyte subsets and other parameters in 32 patients undergoing radiation therapy for solid cancer. With monoclonal antibody techniques, we studied both T- and B-lymphocytes; cell suspensions were analyzed by means of a Facs Spectrum III Ortho (Ortho-Diagnostic) unit. The first control was performed right after the beginning of radiotherapy, when the dose to the patients was 50 Gy or higher. The second control was performed at 40 Gy because all patients received this dose. 30% of the patients exhibited lymphopenia from the beginning of the study; at 40 Gy the number of T-lymphocytes was low and helper/suppressor ratio was altered. A variable response of B-cells was observed, although all patients exhibited restoration of normal values at 6 months. Four patients only suffered from side-effects: a patient with tongue cancer presented oral mycosis, and a woman--treated for breast cancer--presented vaginal mycosis. Two cases of cystitis were also observed, after 18 Gy, in patients with uterine carcinoma undergoing pelvic irradiation. Disease progression was observed in 2 patients with head and neck cancer, while 3 patients died from lung cancer progression. Another one, with head and neck cancer, died because of heart failure.

Adult↗

Selective estrogen receptor modulators and postmenopausal health.

SERMs are a class of drugs with mixed estrogen agonist/antagonist effects that have great potential at targeting changes seen in the postmenopausal period. Raloxifene is effective in preventing bone loss and may prevent fractures in postmenopausal osteoporosis. It induces changes in lipoprotein concentrations that should be cardioprotective. It has no stimulatory effect on the uterus and is well tolerated. Raloxifene is an attractive alternative to HRT in preventing postmenopausal bone loss, especially for women that are more concerned about the risk of breast cancer or vaginal bleeding. Unanswered questions include raloxifene's effect on fracture incidence, cardiac events, and dementia; long-term safety data are also needed. Its potential role in the primary prevention of breast cancer also needs large, long-term studies. Tamoxifen has been used traditionally as adjuvant therapy for breast cancer, but new data indicate that it is effective in the primary prevention of breast cancer in women at increased risk. Its effects on bone and lipoproteins are attractive complementary effects when used in the subset of women at increased risk for breast cancer. New generations of SERMs are being developed that may have more potent estrogen agonist effects on bone and cardiovascular disease, or more potent antiestrogen effects, especially at the breast. There will likely be a selection of SERMs available, and the choice of SERM for a woman will be tailored to her specific issues and risk profile.

Breast Neoplasms↗

A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.

BACKGROUND: The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. We compared letrozole with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. METHODS: The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. RESULTS: A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. CONCLUSIONS: In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. (ClinicalTrials.gov number, NCT00004205.)

Adult↗

The attitudes of women and feasibility of screening for ovarian and endometrial cancers in inner city practices.

The study aimed to assess the attitudes of women and the feasibility of screening for ovarian and endometrial cancers using vaginal ultrasound should screening prove to be effective. A total of 4873 women aged 45-74 were registered with 9 general practices in inner London. Of these, 1469 (30%) were ineligible for screening for ovarian and endometrial cancers as they proved to be the wrong age, had moved, or had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The proportion of ineligible women varied between practices (24-39%) (P < 0.001). The adjusted response rate to a questionnaire on attitudes to ovarian and endometrial screening was 56% (1833/3360). Of the women, 1395 (76%) were willing to be screened with a significant difference between age groups, those over 65, at increased risk, being less willing (P < 0.001). Non-caucasians were more willing to be screened (P < 0.001) but educational attainment did not influence attitude to screening. Those women who were not very worried about vaginal instrumentation were more willing to be screened than those who were very worried (P < 0.001). The uptake rate for ovarian and endometrial screening, which is currently of unproven value, was 43% (1480/3360) with a significant difference between practices (33-49%) (P < 0.01).

Aged↗

Radical vaginal hysterectomy with extraperitoneal pelvic lymphadenectomy in cervical cancer.

OBJECTIVE: The aim of this work was to examine three types of radical vaginal hysterectomy with different degrees of radicality, performed in order to reduce surgical complications and sequelae in different indications, and to test the feasibility of a new simple and quick technique for extraperitoneal pelvic lymphadenectomy to be used in combination with radical vaginal hysterectomy for treatment of cervical cancer. In this way the advantages of vaginal surgery (e.g.: unnecessary general anaesthesia, reduced surgical trauma, applicability to obese and poor surgical risk patients, fast time-saving procedure) can be preserved. METHODS: We compared retrospectively the long-term results of radical vaginal and radical abdominal operations in a large series of stage IB-IIA cervical cancer patients treated at our institution in Florence from 1968 to 1983. Furthermore, we analysed the results of our experience from 1995 to 1998, when we performed extraperitoneal pelvic lymphadenectomy, followed by radical vaginal hysterectomy, on 48 patients affected by cervical cancer. Extraperitoneal pelvic lymphadenectomy was performed through two small abdominal incisions (6-7 cm). Twenty-two patients (45%) were obese (BMI>30 kg/m2) and 20 were poor surgical risks. FIGO stage was: IB1 in 18 cases, IB2 in eight, IIA in six, IIB in 12, IIIB in four. Neoadjuvant chemotherapy was given in 12 cases and preoperative irradiation was given in ten. General and regional anaesthesia were used in 30 (62.5%) and in 18 (37.5%) cases, respectively. RESULTS: As for past experience, in stage IB the five-year survival of 356 patients who underwent radical vaginal hysterectomy and that of 288 who had radical abdominal hysterectomy with pelvic lymphadenectomy were 81% and 75%, respectively (p<0.05). Surgical complications were fewer with no mortality in the first group. In stage IIA, survival rates were 68% for radical vaginal hysterectomy and 64% for radical abdominal hysterectomy, in 76 and 64 cases, respectively (p=n.s.). As for the more recent experience, median operative time for extraperitoneal pelvic lymphadenectomy was 20 minutes for each side (range 15-36). In each patient a median of 26 lymph nodes were removed (range 16-48). Positive nodes were found in 12 cases (25%). Median operative time for radical vaginal hysterectomy was 40 minutes (range 30-65). Extraperitoneal pelvic lymphadenectomy complications included: lymphocyst, five cases (10%) and retroperitoneal hematoma, one (2%); all occurred at the beginning of the experience. Radical vaginal hysterectomy complications included: ureteral stenosis, one (2%) and uretero-vaginal fistula, one (2%). All complications occurred in patients who received radiotherapy or chemotherapy preoperatively. Median hospital stay was ten days (range 6-20). CONCLUSIONS: The results of our work demonstrate that our technique for extraperitoneal pelvic lymphadenectomy shows a good applicability to cervical cancer patients submitted to radical vaginal hysterectomy, which has a high rate of cure for stage IB and IIA as shown by our past experience. The procedure of extraperitoneal pelvic lymphadenectomy was quick, easy, and safe, and its realization was not detrimental to the advantages of radical vaginal hysterectomy. Our experience supports the continued use of this combined extraperitoneal and vaginal approach in the treatment of cervical cancer. Moreover, the three classes of radical vaginal hysterectomy allow tailoring the type of the operation to the clinical and physical characteristics of the patients.

Adult↗

[Screening for ovarian carcinoma].

Approximately 1 in 70 women in the USA will develop ovarian cancer in their lifetime. As the incidence of ovarian cancer is higher than that of cervical cancer, an effective screening program is indicated from a medical point of view. This article examines the reduction in ovarian cancer mortality that might be achieved if we can develop a screening test for the detection of this disease during its preclinical phase. Until recently the only potential screening test for ovarian cancer was vaginal examination. With pelvic examination small ovarian lesions are often missed. Ultrasound examination of the ovaries is a much more reliable method for examining the ovary than gynecologic palpation. The combination of serum CA125 measurement with ultrasound examination offers the most specific and sensitive method for the early detection of ovarian cancer. Question concerning the optimal population to screen remain unanswered. If a screening protocol for ovarian cancer is available, demonstration that it results in a reduction in mortality in the screened population will be required. This will only be obtained by performing a large population based, randomised controlled study. Therefore, a simple and reliable screening test for the early detection of ovarian cancer is still urgently required.

Adult↗

Abnormal vaginal bleeding from endometrial polyps in a woman receiving tamoxifen therapy for breast cancer: report of a case.

We report herein the case of a women receiving tamoxifen therapy for breast cancer who developed vaginal bleeding, subsequently found to be caused by unusual endometrial polyps. Upon presentation, ultrasonography and magnetic resonance imaging (MRI) demonstrated a tumor within the uterus. A hysterectomy was performed, and macroscopic examination showed polyp-like lesions of the uterus. Histologically, these polyps demonstrated cystically dilated glands and stromal proliferation, and were diagnosed as endometrial polyps. Although tamoxifen has few side effects, any signs or symptoms of gynecological abnormalities should be carefully evaluated in patients on long-term tamoxifen therapy.

Antineoplastic Agents, Hormonal↗

Dosimetric comparison of intensity-modulated, conformal, and four-field pelvic radiotherapy boost plans for gynecologic cancer: a retrospective planning study.

PURPOSE: To evaluate intensity-modulated radiation therapy (IMRT) as an alternative to conformal radiotherapy (CRT) or 4-field box boost (4FB) in women with gynecologic malignancies who are unsuitable for brachytherapy for technical or medical reasons. METHODS: Dosimetric and toxicity information was analyzed for 12 patients with cervical (8), endometrial (2) or vaginal (2) cancer previously treated with external beam pelvic radiotherapy and a CRT boost. Optimized IMRT boost treatment plans were then developed for each of the 12 patients and compared to CRT and 4FB plans. The plans were compared in terms of dose conformality and critical normal tissue avoidance. RESULTS: The median planning target volume (PTV) was 151 cm(3) (range 58-512 cm(3)). The median overlap of the contoured rectum with the PTV was 15 (1-56) %, and 11 (4-35) % for the bladder. Two of the 12 patients, both with large PTVs and large overlap of the contoured rectum and PTV, developed grade 3 rectal bleeding. The dose conformity was significantly improved with IMRT over CRT and 4FB (p < or = 0.001 for both). IMRT also yielded an overall improvement in the rectal and bladder dose-volume distributions relative to CRT and 4FB. The volume of rectum that received the highest doses (>66% of the prescription) was reduced by 22% (p < 0.001) with IMRT relative to 4FB, and the bladder volume was reduced by 19% (p < 0.001). This was at the expense of an increase in the volume of these organs receiving doses in the lowest range (<33%). CONCLUSION: These results indicate that IMRT can improve target coverage and reduce dose to critical structures in gynecologic patients receiving an external beam radiotherapy boost. This dosimetric advantage will be integrated with other patient and treatment-specific factors, particularly internal tumor movement during fractionated radiotherapy, in the context of a future image-guided radiation therapy study.

Dose Fractionation, Radiation↗

[Recurrent carcinoma in situ of the uterine cervix (author's transl)].

Among 228 patients who had previous treatment for carcinoma in situ of the cervix, most by hysterectomy, 3 recurrences in vaginal stumps were detected in women age 36, 46, and 56. In another case a carcinoma in situ of the cervix was found in a 25 year old patient who had a diagnostic and therapeutic conization because of desire for childbearing. The histology of the cone showed no residual carcinoma. Concommitent to the recurrent carcinoma in situ of the cervix a carcinoma of the vulva was detected. Recurrences of carcinoma in situ could occur because of incomplete resection of primary lesion. Wrong classification in the laboratory is possible if the invasion is missed on the microscopic examination and the case therefore receives the wrong treatment. Recurrences which are not true recurrences could arise from multicentric atypical foci of the squamous epitheleum of the -ower female genital tract. These considerations lead to the following recommendations: 1. When the suspected diagnosis carcinoma in situ of the uterine cervix is made a large enough cone biopsy which is appropriately marked is obtained and a complete microscopic examination of the cone must be obtained. 2. A hysterectomy with a large vaginal cuff is the treatment of choice. 3. A careful workup of the operative specimen in the microscopic laboratory is expecially essential. 4. A patient with such previous treatment for carcinoma in situ of the uterine cervix must be urged to continue with regular preventive examinations for cancer. The vaginal stump must be regularly re-examined both by colposcopy and by cytology.

Adult↗