Cerebral hemodynamics during implantation of cardioverter-defibrillator systems

PURPOSE: The prognosis of patients with pelvic wall recurrences after primary therapy of cervical cancer is bad. In selected patients treated exclusively by surgery as primary therapy the 5-year survival rate was between 5 and 25%. Additionally the combination of operation and radiotherapy (CORT) improved the survival so far. We developed a new concept for the treatment of pelvic wall recurrences. This concept includes the combination of radical surgery, interstitial radiation and chemotheray--CORCT (combined operative- and radiochemotherapy). PATIENTS AND METHODS: After radical surgery, interstitial HDR (Ir-192) brachytherapy in afterloading technique (2.5 Gy, 2 fractions/day in 5 days) was performed. Additionally a chemotherapy with cisplatin 25 mg/m2/day in 5 days and 5-fluorouracil 1000 mg/day in 5 days was applicated. RESULTS: After combined operative- and radiotherapy 3 of 3 patients died after treatment within 8 months (median) because of distant metastases. After additive radiochemotherapy 3 of 4 patients had no evidence of disease (NED) after a follow-up period of 14 (12 to 30) months. CONCLUSION: The first treatment results of the new designed combined operative- and radiochemotherapy concept (CORCT) led us to expect an improvement of the prognosis of patients with recurrences of cervical cancer at the pelvic wall.     

How to manage locally advanced primary and recurrent cancer of the uterine cervix: The surgeon's view

Locally advanced cancer of the uterine cervix covers a broad disease spectrum comprising primary tumours of >4 cm in size or FIGO stage >IIA and all local tumour relapses except the rare cases of small recurrences in a retained cervix. Treatment designs have to consider the probability of pelvic and periaortic lymph node metastases and – albeit less frequent in primary disease – distant metastases.Established treatment standards aiming to achieve pelvic and eventually periaortic tumour control are chemoradiation for locally advanced primary disease as well as post-surgical pelvic recurrences, and pelvic exenteration for post-radiation central relapses. A subset of patients with pelvic side wall relapses can now be successfully treated by laterally extended endopelvic resection as well. Based on the current results it is not evident whether neoadjuvant chemotherapy, radical hysterectomy and eventually adjuvant radiation are comparable or superior treatment alternatives for locally advanced intermediate stage cases. Likewise, the benefit of (laparoscopic) surgical staging including the exstirpation of bulky pelvic and periaortic lymph nodes has not been convincingly demonstrated to date. Both surgical treatment concepts need further well-designed prospective randomized trials for their evaluation. From the surgeon's perspective total mesometrial resection, therapeutic lymph node dissection, laterally extended endopelvic resection and new developments in restoration/substitution of pelvic functions have the potential to improve the therapeutic index for defined cohorts of patients suffering from locally advanced cancer of the uterine cervix.     

Stage I seminoma of the testis: long term results and toxicity with adjuvant radiotherapy

AIMS AND BACKGROUND: Pure testicular seminoma has historically been treated with post-orchidectomy radiation therapy with excellent results. Recently, several aspects of the treatment of stage I seminoma have been questioned. We assessed long-term results and toxicity of patients with pure testicular seminoma treated at the Department of Radiation Oncology of S. Chiara Hospital, Trento, METHODS: From 1953 to 1987, 102 patients with stage I pure testicular seminoma were given megavoltage irradiation with curative intent. All patients had a minimum follow-up of 3 years (maximum 37 years, median 13 years). They received a mean para-aortic/pelvic dose of 33.07 Gy (range 23.70-45.20 Gy) with different doses and fields reflecting the change in techniques over a long period of time. RESULTS: The cause-specific actuarial survival at 30 years was 99% and crude survival 67%. One patient had an out-field relapse (inguinal) after a few months and was cured with radiotherapy and chemotherapy. Another patient relapsed with widespread metastases and died after 1 year of progressive disease. Early toxycity was mild and the treatment was well tolerated. Late side effects were reported in 8/102 patients. CONCLUSIONS: In our series adjuvant radiation therapy resulted in cure rates corresponding to those reported in the literature. The 30-year actuarial survival of 99% was extremely good and the toxicity of the treatment was mild. Post-orchidectomy radiation to the para-aortic and ipsilateral pelvic nodes is a safe and effective method of preventing recurrences and is currently to be considered the treatment of choice in stage I testicular seminoma.     

Changes with age in the modulation of natural killer activity of murine leukocytes by gastrin-releasing peptide, neuropeptide Y and sulfated cholecystokinin octapeptide

From Jan. 1993 to Sept. 1995 23 patients suffering from brain metastases from renal cell carcinoma were treated with the Leksell Gamma Knife at the University of Vienna. At the time of diagnosis 13 patients had single and 10 patients presented with multiple metastatic lesions with a total of 44 metastases in MRI scans. Median tumour volume was 5500 cmm (range 100-24000 cmm). Predominant neurological symptoms and signs were different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness, ataxia and CN XII paresis. Fourteen patients received Gamma Knife Radiosurgery (GKRS) with a median dose of 22 Gy (range 8-30 Gy) at the tumour margin. Nine patients underwent a combined treatment of a radiosurgical boost with a median dose of 18 Gy (range 10-22 Gy) at the tumour margin followed by Whole Brain Radiotherapy (total dose 30 Gy/2 weeks). In 20 patients tumour volume reduction up to 30% of the primary tumour volume was found after 4 weeks, evaluated on CT or MRI. A total remission was seen in 4 cases 3 months after GKRS. We achieved a local tumour control of 96%. Rapid neurological improvement after GKRS was seen in 17 patients. The median survival time was 11 months; the one-year actual survival in this unselected group was 48%. Five long term survivors were still alive, 18 patients had subsequently died, 15 of them of general tumour progression. GKRS induces a significant tumour remission accompanied by rapid neurological improvement and therefore provides the opportunity for extended high quality survival. Neither local tumour control was improved nor CNS relapse free survival was prolonged significantly by additional WBRT.     

Molecular and pharmacological characterization of recombinant rat/mice N-methyl-D-aspartate receptor subtypes in the yeast Saccharomyces cerevisiae

PURPOSE: To assess the local control and survival in patients who received pelvic irradiation for locally recurrent rectal carcinoma. METHODS AND MATERIALS: The records of 519 patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1975 to 1985 at a single institute were retrospectively reviewed. These included 326 patients who relapsed locally following previous abdominoperineal resection, 151 after previous low anterior resection, and 42 after previous local excision or electrocoagulation for the primary. No patients had received adjuvant radiation therapy or chemotherapy for the primary disease. Concurrent extrapelvic distant metastases were found in 164 (32%) patients at local recurrence and, in the remaining 355, the relapse was confined to the pelvis. There were 290 men and 229 women whose age ranged from 23 to 91 years (median = 65). Median time from initial surgery to radiation therapy for local recurrence was 18 months (3-138 months). Radiation therapy was given with varying dose-fractionation schedules, total doses ranging from 4.4 to 65.0 Gy (median = 30 Gy) over 1 to 92 days (median = 22 days). For 214 patients who received a total dose > or = 35 Gy, radiation therapy was given in 1.8 to 2.5 Gy daily fractions. RESULTS: The median survival was 14 months and the median time to local disease progression was 5 months from date of pelvic irradiation. The 5-year survival was 5%, and the pelvic disease progression-free rate was 7%. Twelve patients remained alive and free of disease at 5 years after pelvic irradiation. Upon multivariate analysis, overall survival was positively correlated with ECOG performance status (p = 0.0001), absence of extrapelvic metastases (p = 0.0001), long intervals from initial surgery to radiation therapy for local recurrence (p = 0.0001), total radiation dose (p = 0.0001), and absence of obstructive uropathy (p = 0.0013). Pelvic disease progression-free rates were positively correlated with ECOG performance status (p = 0.0001), total radiation dose (p = 0.0001), and previous conservative surgery for the primary (p = 0.02). CONCLUSIONS: Survival is poor for patients who develop local recurrence following previous surgery for rectal carcinoma. Pelvic radiation therapy provides only short-term palliation, and future efforts should be directed to the use of effective adjuvant therapy for patients with rectal carcinoma who are at high risk of local recurrence.     

Intestinal lipid esterification and aging in mice and rats

BACKGROUND AND PURPOSE: The risk of side effects of low activity (i.e. <20 mCi) Iodine-125I (125I) interstitial radiotherapy was analyzed in patients with low-grade gliomas. MATERIALS AND METHODS: Permanent (247 patients) or temporary 125I-implants (268 patients) were used with a median reference dose of 60 Gy and 100 Gy, respectively, which was calculated to the outer rim of the tumour. The mean dose rate for temporary implants was low (median, 10 cGy/h). Risk factors were obtained from the multivariate proportional-hazards model. RESULTS: Radiogenic complications occurred in 39/515 patients (28 patients with transient symptoms and 11 patients with progressive symptoms). The most important risk factor was the volume of the intratumoural 200 Gy isodose. Available experimental data have associated a high dose zone in this range with the size of the treatment induced radionecrosis. Rapid tumour shrinkage (decrease of the tumour volume > or =50%) within the first 6 months with subsequent centripetal movement of non-pathologic tissue into the high dose zone and a reimplantation were additional risk factors. Radiation injury after rapid tumour shrinkage could be better avoided with temporary implants. A 200 Gy isodose volume <4.5 ml corresponded to an estimated risk of radiogenic complications <3%. There was a steep increase of the risk beyond this limit. Translation of the 200 Gy isodose volume in terms of the treatment volume and the reference dose allows rational treatment planning. The estimated risk of a temporary implant with an applied reference dose of 60 Gy and a treatment volume <23 ml was <3%. CONCLUSIONS: The intratumoural necrotizing effect of a low activity 125I implant limits its application to small treatment volumes. Radiation injury outside the treatment volume can be better avoided with temporary implants in the case of rapid tumour shrinkage.     

Port-site recurrences following laparoscopic operations for gynaecological malignancies

OBJECTIVE: To determine the frequency of port-site recurrences following laparoscopic surgical treatment of gynaecological malignancies metastatic at the time of surgery. DESIGN: Retrospective review of metastatic primary and recurrent gynaecological malignancies. RESULTS: Twenty-five women were studied. Twenty-four had metastatic disease at the time of laparoscopic surgery, 22 in association with a primary malignancy (cervix: n = 12, ovary: n = 7, endometrium: n = 3), and two in association with recurrent ovarian cancer; all received pelvic or extended field radiation or chemotherapy after surgery. One woman with Stage IIIC ovarian cancer, disease-free at the completion of neoadjuvant chemotherapy following laparotomy by a general surgeon, was included; she developed scalene node metastases 18 months after definitive laparoscopic surgery. Seventy-one 5 mm trocars and fifty 10 mm trocars (total n = 121) were used for surgery; thirty-one 10 mm trocar sites and forty-four 5 mm sites (total n = 75) received post-operative treatment with chemotherapy (n = 49) or radiation (n = 26). Four women (16%) developed recurrences in association with endometrial (n = 2) and cervical (n = 2) cancer at six trocar sites. All recurrences were associated with abdominopelvic and/or distant metastases, and all occurred at untreated 5 mm trocar sites. The difference in recurrence rates between 5 mm and 10 mm trocar sites (chi(2) = 6; P < 0.025), and between treated and untreated trocars (chi(2) = 5; P < 0.05) were both statistically significant (McNemar's test), but the effects of treatment and trocar size on the port-site recurrence rate were confounded. CONCLUSIONS: Port-site recurrences are local manifestations of disseminated disease that result from the enhancement of tumour growth characteristic of healing tissues and can be prevented by appropriate post-operative therapy.     

Survival in patients with primary soft-tissue sarcomas treated within 6 years

Since 1988, treatment strategies for our sarcoma patients have been determined by the same team and operations performed by one surgeon. The aim of this study was to analyse prognostic data on local recurrence and survival of 101 consecutive patients who presented in our institution with the primary tumour manifestation. After a median follow-up of 35 months, the local recurrence rate was 13.5%, the mean survival time was 68 months and the 5-year survival rate was 83%. Besides positive lymph nodes (only 3 patients) the quality of resection significantly influenced local recurrences (P < 0.05). Univariate predictors of mortality were tumour grade (P < 0.01), tumour size (P < 0.05), distant metastases (P < 0.01), and resection quality (P < 0.01). Multivariate predictors of mortality consisted of grade (P < 0.0001), positive lymph nodes (P < 0.001) and resection quality (P < 0.01). In this homogeneous group of patients, excellent recurrence and survival rates could be achieved. An optimized surgical treatment not only reduces the rate of local recurrences but also augments survival time.     

Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial

BACKGROUND: Colon cancer is curable by surgery, but cure rate depends on the extent of disease. We investigated whether adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer. METHODS: In a prospective randomised trial, 254 patients with colon cancer were randomly assigned postoperative ASI or no adjuvant treatment. ASI was three weekly vaccinations starting 4 weeks after surgery, with a booster vaccination at 6 months with 10(7) irradiated autologous tumour cells. The first vaccinations contained 10(7) BCG organisms. We followed up patients for time to recurrence, and recurrence-free and overall survival. Analysis was by intention to treat. FINDINGS: The 5.3 year median follow-up (range 8 months to 8 years 11 months) showed 44% (95% CI 7-66) risk reduction for recurrence in the recurrence-free period in all patients receiving ASI (p=0.023). Overall, there were 40 recurrences in the control group and 25 in the ASI group. Analysis by stage showed no significant benefit of ASI in stage III disease. The major impact of ASI was seen in patients with stage II disease, with a significantly longer recurrence-free period (p=0.011) and 61% (18-81) risk reduction for recurrences. Recurrence-free survival was significantly longer with ASI (42% risk reduction for recurrence or death [0-68], p=0.032) and there was a trend towards improved overall survival. INTERPRETATION: ASI gave significant clinical benefit in surgically resected patients with stage II colon cancer. ASI has minimal adverse reactions and should be considered in the management of stage II colon cancer.     

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     

Radical vulvectomy with postoperative irradiation for vulvar cancer: therapeutic implications of a central block

PURPOSE/OBJECTIVE: To report the long-term results of vulvectomy, node dissection, and postoperative nodal irradiation using a midline vulvar block in patients with node positive vulvar cancer. METHODS AND MATERIALS: From 1971 through 1992, 27 patients with carcinoma of the vulva and histologically involved inguinal lymph nodes were treated postoperatively with radiation therapy after radical vulvectomy and bilateral lymphadenectomy (n = 25), radical vulvectomy and unilateral lymphadenectomy (n = 1), or hemivulvectomy and bilateral lymphadenectomy (n = 1). Federation Internationale de Gynecologic et d'Obstetrique stages were III (n = 14), IVA (n = 8), and IVB (n = 5) squamous cell carcinoma. Inguinal lymph nodes were involved with tumor in all patients (average number positive = 4, range 1-15). Postoperative irradiation was directed at the bilateral groin and pelvic nodes (n = 19), unilateral groin and pelvic nodes (n = 6), or unilateral groin only (n = 1). These 26 patients had the midline blocked. In addition, one patient received irradiation to the entire pelvis and perineum. Doses ranged from 10.8 to 50.7 Gy (median 45.5) with all patients except 1 receiving > or = 42.0 Gy. RESULTS: Actuarial 5-year overall survival and disease-free survival estimates were 40% and 35%, respectively. Recurrences developed in 63% (17/27) of the patients at a median of 9 months from surgery (range 3 months to 6 years) and 15 of these have died; two patients with recurrences are surviving at 24 and 96 months after further surgery and radiation therapy. Central recurrences (under the midline block) were present in 13 of these 17 patients (76%), either as central only (n = 8), central and regional (n = 4), or central and distant (n = 1). Additionally, three patients developed regional recurrences and one patient developed a concurrent regional and distant relapse. One patient developed a squamous cell cancer of the anus under the midline block 54 months after the initial vulvar cancer and an additional patient developed transitional cell carcinoma of the ureter (outside the radiation field) 12 months after diagnosis. Factors associated with a decreased relapse-free survival included increasing Federation Internationale de Gynecologic et d'Obstetrique stage (p = 0.01) and invasion of the tumor into the subcutaneous (SC) fat or deep soft tissue (p = 0.05). Chronic lower extremity edema developed in four patients, but there have been no other complications. CONCLUSIONS: Radical vulvectomy has often been considered sufficient central treatment for vulvar carcinoma, with postoperative irradiation directed only to the nodes. Although designed to protect the radiosensitive vulva, use of a midline block in this series resulted in a 48% (13/27) central recurrence rate, much higher than the 8.5% rate previously reported with this technique. Routine use of the midline block should be abandoned and, instead, postoperative irradiation volumes should be tailored to the individual patient.     

Complete remission after radiotherapy for recurrent rectal cancer

Although the efficacy of radiotherapy for the palliation of recurrent or inoperable cancer has been proven, it results in complete tumor remission only rarely. We report a case of pelvic recurrence in which complete histological remission followed radiotherapy. A 68-year-old man developed a small pelvic recurrence near the rectal stump 8 months after a Hartmann procedure for rectal cancer. Histologic examination of the biopsy specimens revealed adenocarcinoma consistent with the primary tumor. He received radiotherapy to the whole pelvis, with a total dose of 39.4 Gy administered in 22 fractions over 4 weeks, with a continuous infusion of 5-fluorouracil as a radiosensitizer. After regression of the tumor was confirmed, resection of the pelvic recurrence was performed. Histologic examination of the resected specimen revealed no tumor. Thirty-six months after the second operation, the patient was alive with no evidence of disease. The experience of our case and a review of the literature suggests that small pelvic recurrences may be more responsive to radiotherapy than larger ones.     

Postoperative radiation for cervical cancer with pathologic risk factors

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.     

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.     

The Medical Devices Agency

Gossypiboma (retained surgical sponge) is a rare but preventable occurrence. In this case it presented as a chronic abdominal mass which simulated a primary small bowel tumour. The findings on pelvic ultrasonography were typical for this condition and the role of plain abdominal radiology in the gynaecological patient are highlighted.     

Stability of chromatin in a cell-free system of Drosophila embryos

OBJECT: Certain patients, for example, elderly high-risk surgical patients, may be unfit for radiofrequency thalamotomy to treat parkinsonian tremor. Some patients, when given the opportunity, may choose to avoid an invasive surgical procedure. The authors retrospectively reviewed their experience using gamma knife radiosurgery for thalamotomies in this patient subpopulation: 1) to determine the efficacy of the procedure; 2) to see if there is a dose-response relationship; 3) to review radiological findings of radiosurgical lesioning; and 4) to assess the risks of complications. METHODS: Radiosurgical nucleus ventralis intermedius thalamotomy using the gamma knife unit was performed to make 38 lesions in 24 men and 10 women (median age 73 years, range 58-87 years) over a 5-year period. A median radiation dose of 130 Gy (range 100-165 Gy) was delivered to 38 nuclei (four patients underwent bilateral thalamotomy) using a single 4-mm collimator following classic anatomical landmarks. Twenty-nine lesions were made in the left nucleus ventralis intermedius thalamus for right-sided tremor. Patients were followed for a median of 28 months (range 6-58 months). Independent neurological evaluation of tremor based on the change in the Unified Parkinson's Disease Rating Scale tremor score was correlated with subjective patient evaluation. Comparison was made between a subgroup of patients in whom "low-dose" lesions were made (range 110-135 Gy, mean 120 Gy) and those in whom "high-dose" lesions were made (range 140-165 Gy, mean 160 Gy) for purposes of dose-response information. Four thalamotomies (10.5%) failed, four (10.5%) produced mild improvement, 11 (29%) produced good improvement, and 10 (26%) produced excellent relief of tremor. In nine thalamotomies (24%) the tremor was eliminated completely. The median time to onset of improvement was 2 months (range 1 week-8 months). Concordance between an independent neurologist's evaluation and that of the patient was statistically significant (p < 0.001). Two patients who underwent unilateral thalamotomy experienced bilateral improvement in their tremor. There were no neurological complications. There was better tremor reduction in the high-dose group than in the low-dose group (p < 0.04). CONCLUSIONS: Although less effective than other stereotactic techniques, gamma knife radiosurgery for thalamotomy offers tremor control with minimal risk to patients unsuited for open surgery.     

Effect of adjuvant iridium-192 brachytherapy on the survival of patients with malignant gliomas

The effect of iridium-192 brachytherapy (BRTX) on the survival of patients with malignant gliomas was evaluated in 83 patients with malignant gliomas (42 astrocytoma grade III, 41 glioblastoma multiforme) over a period of 8.5 years. Fifty patients (Group 1) received only standard external beam radiotherapy (EBRT) (mean dose 51.5 +/- 12.4 Gy in 2.0 Gy fractions), and 33 patients (Group 2) received EBRT (mean dose 51.0 +/- 10.8 Gy) combined with BRTX (mean dose 50.2 +/- 13.2 Gy, dose rate of 0.3-0.4 Gy/hr). The median survival periods for patients in Groups 1 and 2 were 12.2 and 23.7 months, respectively (p = 0.0145). The median survival for 17 patients in Group 2 with glioblastoma multiforme was 21.9 months. Using BRTX as an adjuvant to EBRT appeared to confer survival benefits compared to only EBRT (p = 0.0284). Univariate and multivariate analysis identified the variables of histological diagnosis, location, Karnofsky performance status, and BRTX as relevant risk factors for survival time (p < 0.05 for each factor). Among these factors, BRTX was the most important for prolonging survival (p = 0.0015). Adjuvant iridium-192 BRTX and conventional EBRT appears to greatly improve the survival time of patients with malignant gliomas compared to only EBRT and may be the treatment of choice in selected patients with tumors located in deep-seated or eloquent areas.     

Recurrences from malignant parotid salivary gland tumors

The clinical course of 130 patients treated for malignant parotid tumors at the three institutions have been reviewed. Fifty-six of these 130 patients developed recurrences following their primary treatment by a surgical procedure. There were a total of 109 recurrences among these 56 patients. The average number of recurrences was two per patient. The average survival from first recurrence was 3.7 years, with the median survival 2 years. The range of survival was 0.5 to 17 years. Once recurrence developed, treatment was by surgery, radiation therapy, chemotherapy, or a combination. Of 56 patients with recurrence, 33 are dead and 9 patients are alive with disease. Fourteen patients are alive and well with no evidence of disease. These NED patients had an average number of 1.6 recurrences and a median survival to date of only 3 years. Our study indicates that for the majority of patients who develop recurrence, survival is relatively short and treatment is usually ineffective in three of four patients. The authors conclude that after a surgical procedure for malignant salivary gland tumors, a trial of wide field postoperative radiation therapy to high dose should be considered as part of the initial treatment.     

Successful multimodal therapy of a locally advanced non-small-cell bronchial cancer

HISTORY AND CLINICAL FINDINGS: A chest radiogram, performed on a 60-year-old man with unproductive cough for 3 months, showed a space-occupying lesion in the right upper lobe, and breath sounds were diminished in this area. He had been a heavy smoker. His general condition and nutritional state were good. INVESTIGATIONS: Computed tomography, skeletal scintigraphy, bronchoscopy with biopsy and mediastinoscopy established the diagnosis of a locally advanced non-small-cell bronchial carcinoma (stage IIIB or T2N3M0). TREATMENT AND COURSE: Combined adjuvant treatment was begun in the hope of improving the median survival time of 8 months predicted for this tumour stage. After two cycles of a combined chemotherapy scheme (ifosfamide, carboplatin, etoposide) he received hyperfractionated-accelerated radiotherapy (total dose 45 Gy; 1.5 Gy twice daily) together with carboplatin and vindesine. This was followed by a right upper lobectomy with lymphadenectomy. Full remission was confirmed in both the resected specimen and the lymph nodes. The patients remains free of tumour 30 months after the diagnosis. CONCLUSION: Neoadjuvant treatment can significantly improve the prognosis of non-small-cell bronchial carcinoma in stage III. Such patients should therefore be treated according to the appropriate study protocol, if possible.     

United States Thrombotic Thrombocytopenic Purpura Apheresis Study Group (US TTP ASG): multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange

PURPOSE: Clinical experiences in interstitial 192-iridium HDR brachytherapy for the treatment of unresectable pancreatic carcinoma are presented. Brachytherapy has been used as boost irradiation in a multimodality treatment concept together with external radiotherapy and simultaneous chemotherapy. Practicability during clinical routine, tolerability and toxicity of treatment are investigated. PATIENTS AND METHODS: Nineteen patients (9 female, 10 male, median age 67 years) with unresectable carcinoma of the pancreas have been treated with interstitial brachytherapy. Distribution according to UICC stages showed 4, 10 and 5 patients in stage II to IV respectively. In all cases afterloading technique with 192-iridium in HDR-modus was used. A total dose of 10 to 34 Gy to the reference isodose was delivered (single dose 1.88 to 5 Gy, median 2.5 Gy). Brachytherapy was followed by external radiotherapy, delivering an additional dose of 40 to 58 Gy. Nine patients received simultaneous chemotherapy (5-fluorouracil, leucovorin). Treatment planning was performed based on CT scans, allowing spatial correlation of isodose curves to the patient's anatomy. RESULTS: Median survival time was 6 months. A trend of lower survival rates with advanced stage of disease (median survival stage IV 4 months, stage II and III 6.5 months) was seen. Local control rate was 70%. Brachytherapy treatment was well tolerated, severe acute side effects were not observed. One patient developed pancreatic fistulae 4 months and 1 patient a gastric ulcer 7 months after treatment. Pain release was achieved in all patients. CONCLUSIONS: 192-iridium HDR-brachytherapy is an effective tool in the treatment of unresectable pancreatic carcinoma with a high rate of local control and a low rate of side effects and is comparable IORT or seed implantation.