Interim report on the radiosurgical treatment of cerebral arteriovenous malformations. The influence of size, dose, time, and technical factors on obliteration rate

During the authors' initial 4-year experience with radiosurgery using the Leksell cobalt-60 gamma unit, they treated 121 patients with cerebral arteriovenous malformations (AVMs). The radiosurgical dose to the margin of the nidus was 20 Gy for lesions less than 2.0 cm in diameter (volume < or = 4.2 cm3); 18 Gy for malformations 2.1 to 3.0 cm in diameter (volume 4.2-14.1 cm3); and 16 Gy for malformations greater than 3.0 cm (volume > 14.1 cm3). Fifty-one patients underwent follow-up angiography between 1 and 3 years after treatment, and complete obliteration of the nidus was confirmed in 38 (74.5%) of these patients. Thirty-two (74.4%) of 43 AVMs with volumes of 10 cm3 or less and six (75%) of eight larger AVMs (volume 11-30 cm3) showed complete obliteration. Analysis of the time course of AVM nidus shrinkage and obliteration showed that most of the radiosurgically induced effect had occurred by 36 months after treatment. Retrospective analysis of the dose plans for 10 AVMs that were not obliterated by 36 months after gamma knife radiosurgery at the authors' institution (eight cases) or elsewhere (two cases) revealed that six AVMs had not been covered completely by the prescribed isodose. Six (5%) of the 121 patients developed neurological deficits as a direct result of radiosurgical treatment. The authors infer from these data that malformations up to 30 cm3 in volume (approximately 4.0 cm in average diameter) can be treated effectively with an acceptably low complication rate using a radiosurgical dose of 16 Gy to the margin of the nidus. The obliteration rate for the larger malformations that were treated with a dose of 16 to 18 Gy appears to be similar to that for smaller ones treated with 18 to 20 Gy. As more experience accrues using radiosurgery to treat AVMs, patient selection criteria and the variables associated with successful obliteration of the nidus should become more clearly defined.     

Laparoscopy-assisted and -prepared hysterectomy. A series of 80 cases

OBJECTIVE: Our objective was to determine the interest of laparoscopic assisted vaginal hysterectomy. STUDY DESIGN: Between January 1991 to december 1994, 80 patients had laparoscopically assisted vaginal hysterectomy. We reviewed with particular emphasis characteristic indications, complications. RESULTS: Eighty were performed as laparoscopically assisted vaginal hysterectomy. 14 patients (17.5%) had laparotomy conversion; because of size of uterus in 3 cases, suspected ovarian tumor in 3 cases. Pelvic adherences in 4 cases, urinary tract injuries in 1 case, hypercapnia in 1 case, hemorrhage in 2 cases. 9 patients experienced febrile morbidity and 1 urinary infection. 1 patient received 2 units of packed red blood cells. The hospital stay was 5 days for laparoscopically assisted vaginal hysterectomy versus 5.9 for laparotomic hysterectomy. CONCLUSION: Laparoscopically assisted vaginal hysterectomy offers a technique to convert certain abdominal hysterectomies into vaginal hysterectomies with a 17.5% laparoconversion rate.     

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0     

Pathological changes in surgically resected angiographically occult vascular malformations after radiation

OBJECTIVE: The goal of this study was to evaluate the pathological changes associated with radiation treatment (stereotactic radiosurgery or conventional irradiation) of angiographically occult vascular malformations (AOVMs). METHODS: Eleven patients underwent surgical resection of an AOVM in the mesial temporal lobe, brain stem, thalamus, or basal ganglia after previous radiation treatment. The indications for surgery were recurrent symptomatic bleeding from the lesion in 10 patients and recurrent intractable seizures in 1 patient. Radiation was used as the initial therapy because the risk of surgical resection was deemed too high. Three patients received conventional radiation therapy of 3000 to 5400 rads at an outside institution. One patient received radiosurgery with the gamma knife at another institution using a dose of 15 Gy to the margin. The remaining 7 patients received stereotactic radiosurgery with a helium-ion particle beam. The dose range was from 18 to 26 Gy equivalents. The interval from radiation to surgical resection ranged from 1 to 10 years, with a mean of 3.5 years. These lesions were compared with 10 nonirradiated cavernous malformations. RESULTS: One irradiated lesion was identified pathologically as a true arteriovenous malformation despite being angiographically occult. This lesion did not demonstrate significant changes in the vasculature but did have radiation necrosis of the surrounding brain 5 years after 25 Gy equivalents of helium-ion radiosurgery. Two other specimens were too small to identify the type of vascular malformation adequately. Of the remaining eight malformations identified as cavernous malformations, six showed a combination of marked fibrosis of the vascular channels, fibrinoid necrosis, and ferrugination. However, the fibrinoid necrosis was the only finding unique to the irradiated lesions compared with nonirradiated controls. All the irradiated lesions still had patent vascular channels; none were completely thrombosed. CONCLUSION: Radiosurgery or conventional radiation therapy did not cause histologic vascular obliteration in intracranial AOVMs evaluated 1 to 10 years (mean 3.5 yr) after radiation delivery. It should be recognized that these patients are irradiation failures who may not be representative of all irradiated patients. However, recurrent bleeding from AOVMs may relate to poor radiation response in some patients.     

Trends in surgical management of astrocytomas and other brain gliomas

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.     

Epidermal thickness measurements in vaginal intraepithelial neoplasia. A basis for optimal CO2 laser vaporization

The current management of vaginal intraepithelial neoplasia (VAIN) often involves the use of laser vaporization. A study was performed to measure the epithelial thickness in both premenopausal and postmenopausal women with various grades of VAIN to determine the optimum depth of tissue destruction if laser vaporization is used for therapy. Hematoxylin and eosin-stained tissue sections were examined with light microscopy and measurements made with a calibrated micrometer. Sixty-three biopsies from 56 patients were studied. Patients' ages ranged from 22 to 84 years, with a mean of 56. Thirty-six had a prior history of cervical neoplasia. Thirty-nine patients (70%) had VAIN III, 10 had VAIN II, and the remaining 7 patients had VAIN I lesions. The involved epithelium varied from 0.10 to 1.4 mm in thickness, with a mean of 0.46. Noninvolved vaginal epithelium varied in thickness from 0.10 to 0.70 mm, with a mean of 0.28. Koilocytosis was noted in only 9 of the 63 biopsy specimens. In comparing the thickness of involved epithelium in a given patient to that of an adjacent area of normal-appearing epithelium, the epithelium containing VAIN tended to be thicker. The recommended depth of epithelial destruction with laser vaporization in the literature varies widely and appears to have largely an empiric basis. Our study attempted to provide a scientific basis for laser destruction of these lesions. The results obtained indicate that epithelial destruction to a depth of 1.5 mm, including the zone of thermal necrosis, should be sufficient to destroy epithelium containing VAIN without damage to surrounding structures.     

Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience

OBJECTIVE: Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment. METHODS: All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr). RESULTS: Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery). CONCLUSION: Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.     

Vaginal hysterectomy for the large uterus

OBJECTIVE: To assess the feasibility and safety of performing vaginal hysterectomy on enlarged uteri the equivalent of 14 to 20 weeks of gestation in size. DESIGN: A prospective observational study. SETTING: The Royal Free Hospital, London. PARTICIPANTS: Fourteen consecutive women undergoing vaginal hysterectomy for uterine fibroids up to 20 weeks in size. INTERVENTIONS: Vaginal hysterectomy with or without bilateral salpingo-oophorectomy or oophorectomy. MAIN OUTCOME MEASURES: Uterine size and weight, techniques used to reduce uterine size, surgical outcome, operative time, estimated operative blood loss, intra- and post-operative complications, duration of hospitalisation. RESULTS: The mean uterine size was 16.3 weeks (range 14 to 20 weeks). All hysterectomies were completed successfully by the vaginal route. The uteri weighed 380 to 1100 g, with a mean of 638.7 g. Bisection combined with myomectomy and morcellation were used in most cases to obtain reduction in uterine size, whereas coring was only utilised in two cases. The mean operating time was 84.3 min with a range of 30 to 150 min. The only complications were transient haematuria (n = 6) and superficial vaginal grazes (n = 5). One of the women required a blood transfusion. The mean post-operative hospital stay was 3.7 days (range 2 to 9 days). CONCLUSION: Enlargement of the uterus to a size equivalent to 20 weeks of gestation should no longer be considered a contraindication to vaginal hysterectomy. Many more hysterectomies should be carried out vaginally without resorting to abdominal or laparoscopic surgery.     

Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL

OBJECTIVES: Most men diagnosed with prostate cancer in 1998 presented with a normal digital rectal examination (DRE) and minimal elevations in serum prostate-specific antigen (PSA) (less than 10 ng/mL). Considerable attention is often given toward identifying small hypoechoic (less than 0.2 cm3) lesions at the time of transrectal ultrasound-guided prostate biopsy. We sought to determine the significance of these lesions and whether an additional biopsy of this area is clinically useful. METHODS: A prospective data base containing detailed information on 614 biopsies performed by a single urologist was examined. All patients with a hypoechoic lesion underwent sextant prostate biopsy plus a separately labeled core directed through the hypoechoic area. Eighty-one patients who fit the following criteria were assessed: PSA less than 10 ng/mL, normal DRE, and hypoechoic lesion volume less than 0.2 cm3. RESULTS: The mean age of this group was 63.5 years, and the mean PSA was 7.1 ng/mL. Of the 81 patients with small hypoechoic lesions, 20 (24.7%) were positive for cancer in at least one prostatic core. Of the 81 hypoechoic area biopsies (HABs), 14 (17.3%) were positive for cancer; 1 (1.2%) demonstrated high-grade prostatic intraepithelial neoplasia, and 66 (81 .5%) were negative. In 11 of the patients (78.6%) with positive HABs, at least one additional core was positive for cancer. In 3 of the patients (21.4%) with positive HABs, no additional cores were positive for cancer (P<0.05). CONCLUSIONS: A significant proportion of small hypoechoic lesions in patients with early T1c prostate cancer are positive for malignancy. Although the overall yield of separate hypoechoic area biopsy is low (3.7%), approximately 15% of cancers would be missed if directed HABs were not performed (P<0.05). Identification and biopsy of small hypoechoic lesions are indicated in this group of patients.     

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.     

Radiotherapeutic management of cervical carcinoma that complicates pregnancy

BACKGROUND: Data regarding radiation therapy for pregnant patients with cervical carcinoma are limited. The goal of this study was to assess the effects of pregnancy on tumor control, survival, and morbidity associated with radiation therapy administered to pregnant patients. METHODS: The authors performed a retrospective case-control analysis of 26 women with cervical carcinoma who were diagnosed during pregnancy and treated primarily with radiation therapy. These cases were matched with 26 controls based on age, histology, stage, treatment, and year of treatment. RESULTS: Patients were treated with external beam radiation (mean dose, 46.7 gray [Gy]) and intracavitary radiation (mean dose, 56.5 Gy to Point A). Two patients with Stage IA2 squamous cell carcinoma treated in the third trimester had a planned delay in treatment of 3 weeks, and both infants had an uncomplicated neonatal course. Seven pregnant patients (2 Stage IB1, 5 Stage IB2) underwent radiation after radical hysterectomy was aborted due to positive regional lymph nodes. Three patients diagnosed during the first trimester were treated with radiation with the fetus in situ, and all had spontaneous abortions 20-24 days after the start of radiation (mean dose, 34 Gy). In all these cases, radiation was interrupted for only 3 days or less. There were no statistically significant differences in recurrence rates or survival between the pregnant group and the controls. Short term toxicity was comparable in pregnant and nonpregnant patients and easily controlled. Long term complications were more common in controls (12% in pregnant patients, 27% in controls), but this difference was not statistically significant. Most complications were likely related to radiation techniques (particularly the predominance of cobalt-60). CONCLUSIONS: Planned delay in treatment should be offered to pregnant patients with early stage squamous cell carcinoma in the late second and early third trimester. Patients diagnosed in the first or second trimester who are not good candidates for planned delay in treatment should be given radiation therapy immediately. It may be necessary to reconsider planned radical hysterectomy for pregnant women with Stage IB2 disease due to the high rate of lymph node positivity found on exploration. For patients with advanced disease, radiation therapy appears to be a safe and effective modality.     

Child abuse and neglect investigative process

To clarify the role of postoperative radiotherapy for adenoid cystic carcinoma of the tracheobronchial system (ACC), we analyzed patients treated at the National Cancer Center Hospital, Tokyo. Seven patients with ACC were treated with resective surgery and postoperative radiotherapy from 1962-1990. None of the primary lesions was completely surgically resected. Postoperative irradiation was delivered by standard fractionation at a dose range of 49.2-72 Gy. Four of seven patients lived more than 5 years, up to 21 years, without local recurrence. In contrast, three other patients who showed recurrence within 2 years died of disease before 5 years. Three of four patients who received postoperative irradiation of 60 Gy or more attained local control. One of three patients who received less than 60 Gy failed locally. A high dose of postoperative radiotherapy for patients with a positive surgical margin of ACC seems to improve local control and result in long-term survival.     

Outcome of treatment of upper third vaginal recurrences of cervical and endometrial carcinomas with interstitial brachytherapy

PURPOSE: To describe an original brachytherapy technique using a dedicated intravaginal template for the treatment of vaginal vault recurrences and to evaluate the results of such a treatment. METHODS AND MATERIALS: Between 1978 and 1993, 78 patients with isolated recurrence of cervical or endometrial carcinoma located in the vaginal vault have been treated in Lyon. Initial treatment was surgery alone in 49 cases and irradiation with surgery in 37 cases. Treatment of the vaginal recurrence was performed with interstitial Iridium 192 brachytherapy combined with pelvic external beam radiation therapy in 34 patients. The tumor was implanted with a dedicated intravaginal plastic template. Six parallel metallic needles were implanted in the vaginal vault and afterloaded with Iridium 192 wires of 4 to 6 cm long. The mucosa of the upper half of the vagina received the same dose as the one encompassing the tumor on the 85% isodose of the Paris system. RESULTS: At 5 years the local control rate was 70% and the overall survival rate 56%. Grade 3 complications occurred in 10% of the cases and only in patients who had received irradiation during the initial treatment of the primary tumor. CONCLUSIONS: This brachytherapy technique makes it possible to perform Iridium 192 implants in a difficult situation with a favorable long-term control rate and an acceptable rate of complications.     

Tape stripping induces marked epidermal proliferation and altered TGF-alpha expression in non-lesional psoriatic skin

PURPOSE: This study was performed to establish the classification and the treatment modality for recurrent cervical cancer of the vaginal stump after hysterectomy. PATIENTS AND METHODS: Ninety patients with centrally recurrent cervical cancer of the vaginal stump following hysterectomy were treated with high-dose-rate intracavitary brachytherapy with or without external irradiation. The intervals between primary surgery and vaginal recurrences varied from 3 months to 36 years. Tumor size of the vaginal stump was determined by bimanual rectovaginal examination at the time of recurrence and was classified into three groups, i.e., small (no palpable tumor), medium (less than 3 cm), and large (3 cm or more). RESULTS: The 10-year survival rates for all patients were 52%. Survival was greatly influenced by the tumor sizes of the vaginal stump. The 10-year survival rates of patients with small, medium, and large size tumors were 72, 48, and 0%, respectively. All patients with large size tumors died within 5 years. Of 90 patients, 75 (83%) were determined by physical examination to be free of tumor on at least one visit within 2 months of the completion of treatment (CR). The remaining 15 patients (17%) had physical findings suggestive of residual tumor (Residual). The overall 10-year survival rate for all patients with CR was 63%, compared with 10% for the patients with Residual (P < 0.0001). The incidences of distant metastases of the patients with or without local failure were 55 and 13%, respectively (P < 0.0001). The patients with local failure had significantly higher incidence of metastases. Most patients with small size tumor were treated with brachytherapy alone, and the survival rates of these patients were not improved by combination with external irradiation. CONCLUSION: These results suggest that tumor size was a significant prognostic factor for recurrent cervical cancer of the vaginal stump. Patients with small size tumors were recommended to be treated with brachytherapy alone.     

The value of conventionally fractionated radiotherapy in the local treatment of HIV-related Kaposi's sarcoma

BACKGROUND: During the course of AIDS, 25 to 44% of homosexual patients infected with the human immunodeficiency virus develop Kaposi's sarcoma. Main manifestation is the skin. Response rates of 80 to 100% can be achieved with total dosage up to 50 Gy. Nevertheless, remissions can also be attained with 20 Gy of fractionated radiotherapy. As clinical data on low dose conventional fractionated radiotherapy are insufficient we analysed the response rates of an overall dose of 20 Gy in conventional fractionation. PATIENTS AND METHODS: From June 1991 to June 1993, 43 patients with 111 HIV-associated Kaposi's sarcoma of the skin or oral cavity were treated. Lesions were irradiated with 5 to 12 MeV electrons or 60Co gamma-rays. The fractionation scheme was 5 times 2 Gy/week for skin and endoral lesions with a total reference dosage of up to 20 Gy. Side effects were assessed during therapy and the therapeutic result 6 weeks after end of treatment. RESULTS: Thirty-eight out of 111 lesions were judged as complete response (CR) (34%), 61/111 as partial response (PR) (55%) and 12/111 were judged as no change (NC) (11%). Overall response (CR + PR) was 89%. Two patients with lesions of oral cavity suffered from RTOG grade-IV mucositis after 10 and 14 Gy. In 71/106 skin lesions (67%), radiation induced RTOG grade-1 reactions were observed. CONCLUSION: In patients with HIV associated Kaposi's sarcoma effective palliation can be achieved by means of radiotherapy with an overall dose of 20 Gy in conventional fractionation. Yet, the fraction of patients with complete responses is with 34 to 47% lower compared with doses above 20 Gy (66 to 100%). With reference to the reported data our results point to a dose-response relationship for Kaposi's sarcoma. Therefore higher total reference doses, e.g. 30 Gy with weekly 5 times 2 Gy or 24 Gy with 5 times 1.6 Gy for mucous lesions, respectively, are suggested as by this mean the complete response rate can be doubled.     

A pilot study on concurrent platinum chemotherapy and intracavitary brachytherapy for locally advanced cancer of the uterine cervix

This study aims to evaluate the feasibility, toxicity and efficacy of concurrent chemotherapy with platinum compounds and brachytherapy, for locally advanced carcinoma of the cervix (Stages IIA/B, IIIA). The hypothesis was that synchronous chemo-brachytherapy may be sufficient to cause down-staging of the tumour, to render it operable, and hopefully improve the prognosis. 36 women with locally advanced cervical cancer were treated with concomitant brachytherapy and chemotherapy before surgery and/or definitive external radiotherapy. All patients received two caesium-137 Selectron MDR applications, 1 week apart. The dose calculated to point A for each implant was 20-25 Gy. Chemotherapy consisting of continuous cisplatin infusion (50 mg m2) and of carboplatin (300 mg m-2) was given simultaneously with intracavitary irradiation during the first and second application, respectively. The combined therapy was followed when feasible by radical hysterectomy, pelvic lymphadenectomy and pelvic radiotherapy. Patients deemed ineligible for surgery because of poor response were given full dose external radiotherapy. 31/36 patients were treated by Wertheim hysterectomy of whom 10 had negative lymph nodes and resection margins. Definitive external radiotherapy was given in the remaining five patients. Overall, 83% were disease free at 2.8 years mean follow-up. The most frequent acute side-effects of chemobrachytherapy were nausea and vomiting. No renal toxicity was observed. Thrombocytopenia was seen in five patients and was responsible for delayed surgery in four patients. Concerning late effects, two patients developed grade 2 intestinal sequelae, two mild frequency and two vaginal stenosis. One rectovaginal and one vesicovaginal fistula developed in two patients; and a third patient had a fistula associated with tumour recurrence. Concurrent brachytherapy and chemotherapy with platinum compounds is well tolerated and effective in reducing tumour bulk before definitive local treatment (surgery or external radiotherapy), in patients with locally advanced carcinoma of the uterine cervix.     

Distinct manifestations of human papillomaviruses in the vagina

To clarify the pathogenic relationships between human papillomavirus (HPV) and vaginal intraepithelial neoplasia (VAIN), we examined 71 vaginal biopsy specimens by histopathology and immunohistochemistry and analyzed the presence of HPV DNA by blot hybridization at Tm - 40 degrees C using an HPV 58 probe (PBM-58 method). We found 27 cases of VAIN in patients with previous hysterectomy or antecedent or concomitant cervical intraepithelial neoplasia (CIN) and 44 cases of VAIN in patients without any abnormal findings on the cervix and the vulva. Histopathologically, 53 of 71 cases were graded as VAIN I and 15 and 3 cases were VAIN II and III, respectively, while 59 cases showed positivity for HPV capsid antigen by immunohistochemistry. Using the PBM-58 method, all 71 VAIN cases harbored a single HPV type at more than 1,000 viral copies per cell. We identified 15 different types (HPV 16, 18, 30, 31, 35, 40, 42, 43, 51, 52, 53, 54, 56, 58 and 66). Furthermore, we molecularly cloned 7 novel prototypes (HPV 59, 61, 62, 64, 67, 69 and 71) from VAIN I. Our results are strongly indicative that HPVs are etiologic agents of VAIN, like in the case of CIN. The distinct manifestations of HPV infection in the vagina are discussed in comparison with those in the cervix.     

The lazaroid U74389G protects normal brain from stereotactic radiosurgery-induced radiation injury

PURPOSE: To test an established model of stereotactic radiosurgery-induced radiation injury with pretreatments of either methylprednisolone or the lazaroid U74389G. METHODS AND MATERIALS: Nine cats received stereotactic radiosurgery with a linear accelerator using and animal radiosurgery device. Each received a dose of 125.0 Gy prescribed to the 84% isodose shell to the anterior limb of the right internal capsule. One animal received no pretreatment, two received citrate vehicle, three received 30 mg/kg of methylprednisolone, and three received 5 mg/kg of U74389G. After irradiation, the animals had frequent neurologic examinations, and neurologic deficits developed in all of them. Six months after the radiation treatment, the animals were anesthetized, and had gadolinium-enhanced magnetic resonance (MR) scans, followed by Evans blue dye perfusion, euthanasia, and brain fixation. RESULTS: Magnetic resonance scans revealed a decrease in the size of the lesions from a mean volume of 0.45 +/- 0.06 cm(3) in the control, vehicle-treated, and methylpredniosolone-treated animals to 0.22 +/- 0.14 cm(3) in the U74389G-treated group. The scans also suggested the absence of necrosis and ventricular dilatation in the lazaroid-treated group. Gross pathology revealed that lesions produced in the untreated, vehicle-treated, and methylprednisolone-treated cats were similar and were characterized by a peripheral zone of Evans blue dye staining with a central zone of a mature coagulative necrosis and focal hemorrhage. However, in the U74389G-treated animals, the lesions were found to have an area of Evans blue dye staining, but lacked discrete areas of necrosis and hemorrhage. CONCLUSION: These results suggest that the lazaroid U74389G protects the normal brain from radiation injury produced by stereotactic radiosurgery.     

Treatment of vaginal dysplasia with loop excision: report of five cases

Five patients with vaginal intraepithelial neoplasia were treated with loop electrosurgical excision procedure on abnormal tissue under general anesthesia; there was no intraoperative or postoperative morbidity. Surgery was performed rapidly and with no blood loss. Pathologic specimens were adequate in all cases; one unsuspected invasive vaginal cancer was found. Further study of this technique seems warranted.