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Purpose. - To analyse outcomes after interstitial brachytherapy of facial periorificial skin carcinomas. Patients and methods. - We performed a retrospective analysis of 97 skin carcinomas (88 basal cell carcinomas (BCCs), 9 squamous cell carcinomas (SCCs)) of the nose, periorbital areas and ears from 40 previously untreated patients (group 1) and 57 patients who had undergone surgery (group 2). The average dose was 55 Gy [50-65] in group 1 and 52 Gy [50-60] in group 2 (mean implantation times: 79 and 74 hours respectively). We calculated survival rates and assessed functional and cosmetic results de visu. Results. - Median age was 71 years [17-97]. There were 29 T1, 8 T2, 1 T3 and 2 Tx tumors in group 1. Tumors were<2 cm in group 2. Local control was 92.5% in group 1 and 88% in group 2 (median follow-up: 55 months [6-132]). Five-year disease-free survival was better in group 1 (91% [75-97]) than in group 2 (80% [62-90]), P=0.23. Of the 34 patients whose results were re-assessed, eight presented pruritus or epiphora. One group 2 patient had an impaired eyelid aperture. Cosmetic results were better in group 1 than in group 2, with respectively 72% (8/11) vs 52% (12/23) of good results and 28 (3/11) vs. 43% (10/23) of fair results. Conclusion. - Brachytherapy provided a high level of local control and good cosmetic results for facial periorificial skin carcinomas that pose problems of surgical reconstruction. Results were better for untreated tumors than for incompletely excised tumors or tumors recurring after surgery.

Purpose: The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures., Patients and Methods: Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray., Results: Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P =.004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival., Conclusion: A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

Introduction: Radiotherapy for the prevention of skin nodules appearing at the sites of aspiration, needle biopsies, chest drains or surgical incisions is the only treatment currently recommended for malignant mesothelioma., Methods: 59 patients suffering from this condition were identified from the database of the Nantes Regional Cancer Centre. 33 received prophylactic irradiation, 25 did not and 1 was excluded., Results: The treated group showed typical demographic and histological features. The delay in initiating radiotherapy ranged from 10 to 123 days and several different treatment regimes were used. In the treated group 7 out of 32 patients developed nodules following radiotherapy with 4 recurrences in the treated and 3 in the untreated areas. The mean interval before recurrence was 9 months (range 3 to 17 months). The recurrence rate was lower in the treated (21%) than in the untreated group (48%;12 out of 25)., Conclusions: The poor results compared with the reference series may be explained by a longer follow-up (mean 12 months), less thorough treatment of all puncture sites and a very long delay before treatment (mean 37 days).

Thirty-five adult patients with high-risk HD (HD) defined by (1) Ann Arbor stage IV or bulky nodal disease (tumor/thorax ratio > 0.45) and (2) no or partial response (PR) (< 75%) to the initial 3 courses of ABVD, received an early intensive therapy with autologous stem cell transplantation (ASCT). Thirty patients were considered as partial responders and 5 as refractory to initial chemotherapy. Conditioning regimen consisted of chemotherapy alone (CBV in 11 patients before 1993, BEAM in 13 patients since 1993) followed by adjuvant radiotherapy: 40 Gy) on the initial sites of bulky disease, or 12 Gy total body irradiation plus 120 mg/kg cyclophosphamide in 11 patients with disseminated extra-nodal disease. All 30 patients in PR at the time of ASCT experienced prolonged complete remission (CR). One patient died in CR from an acute myocardial infarction 48 months after ASCT. Four out of the 5 patients with refractory disease at the time of ASCT experienced rapid progression of HD leading to death in 3 cases. After 6 years of CR post-ASCT, the last refractory patient died of myelodysplastic syndrome diagnosed 2 years after intensive therapy. With a median follow-up for surviving patients of 51 months (range: 11-111), the cumulative probability of 8-year overall survival is 75.6% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). The cumulative probability of 8-year event-free survival is 79.9% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). We conclude that early intensive therapy with ASCT is feasible in patients with high-risk HD and induces a high cure rate in chemosensitive patients. In primary refractory patients, new therapeutic approaches are warranted.

Unlabelled: Tracer pharmacokinetic studies are often used in treatment planning for radionuclide therapy including radioimmunotherapy. This study evaluates the validity of using tracer studies to predict radiation doses from therapy with the same radiolabeled antibody., Methods: Quantitative imaging and blood radioactivity were used to obtain the pharmacokinetics and radiation doses that were delivered to the total body, blood, marrow, lungs, liver, kidneys, thyroid, spleen and tumors. Tracer and therapy data for eight patients with lymphoma and one patient with breast cancer were compared using linear regression statistics. Doses of 131I-labeled antibody for the tracer studies ranged from 0.1 to 0.4 GBq (2 to 10 mCi), and therapy doses ranged from 0.7 to 5.6 GBq (20 to 150 mCi)., Results: Radiation doses to tissues and, in particular, the bone marrow and tumors were reliably predicted from tracer studies. In this group of patients, median dose to marrow from marrow targeting, total body and blood was 9.2 cGy/GBq for tracer studies and 7.6 cGy/GBq for therapy studies with a median difference of 0.5 cGy/GBq. Median dose to tumors was 81.1 cGy/GBq for tracer studies and 70.3 cGy/GBq for therapy studies with a median difference of 5.9 cGy/GBq., Conclusion: In these patients, tracer studies were predictive of the radiation doses from therapy for total body, major organs and tumors. The radiation doses to marrow and tumors, which are the usual determinants of the therapeutic index, correlated well between tracer and therapy studies (r > or = 0.95).

Purpose: Radiotherapy is the standard treatment of anal canal carcinoma. We retrospectively analyzed our experience with 108 patients. Special attention was given in evaluating 51 patients who received concomitant chemotherapy with 5-FU-CDDP., Methods and Materials: From January 1980 to December 1989, 108 patients with anal canal carcinoma were treated with exclusive radiotherapy at the Centre Hospitalier Lyon Sud. There were 11 men and 97 women, mean age was 65 years (30-86). Histologic types were 94 epidermoid carcinomas, 13 basaloid carcinomas, and one adenocarcinoma. The TNM classification (UICC 87) was: 16 T1 (14.8%), 53 T2 (49%), 33 T3 (39.5%), six T4 (5.5%), 77 N0 (71.3%), 20 N1 (18.5%), nine N2 (8.3%) and two N3 (1.8%). Papillon's radiotherapy technique with a Cobalt direct perineal field was used in 82 patients. Ninety-six patients were treated with an interstitial 192Ir implant with a mean delay of 55 days after the end of the radiotherapy. In 59 patients at least one course of either 5-FU-mitomycin (8) or 5-FU-CDDP was added with at least one course concomitantly to the radiotherapy in 53 patients., Results: A complete response in 104/108 patients (96%) was obtained 2 months after the brachytherapy. A locoregional relapse (local and/or pelvic failure) was seen in 18 patients (16.6%) and inguinal node relapse in nine (8.3%). Eight patients with locoregional recurrence and five with inguinal relapse were salvaged. A systemic failure occurred in six (5.5%) patients. Twenty-nine patients died, 16 of progressive disease. One patient died of treatment related toxicity. The overall 5-year survival was 64% +/- 6 and specific survival 72% +/- 8. None of the patient parameters was found to be statistically significant but there was a trend toward longer 5-year survival in T1-T2 patients and in those with well or moderately differentiated tumors. Noteworthy are the same survival rates for N0 and N1-N3 patients (65 vs. 62%). The objective response and the locoregional failure rates were similar in the patients treated with or without chemotherapy. The difference did not reach statistical significance though it was important for the following parameters: overall survival rates for T1-T2 with and without chemotherapy (94 vs. 61%) and for N1-3 patients (73% vs. 27%). The main prognostic factors in this series were differentiation (5-year overall survival with chemotherapy 95% vs. 27% without chemotherapy p = 0.02) and the response at 3 months after treatment initiation, before brachytherapy implant (5-year overall survival for complete responders and "very good responders" 71% vs. 34% in partial responders p = 0.002). The complications rate was acceptable (Grade III 9%, Grade II 14%). Anal preservation was possible in 85% of the patients (92/108). Nine abdominoperineal resection were performed for recurrence and seven for severe necrosis. The T3-T4 group abdomino perineal resection was 23% while it was 9.2% of the T1-T2 group., Conclusion: We confirm that exclusive radiotherapy is the treatment of choice for epidermoid carcinomas of the anal canal. The role of chemotherapy is still unclear.

An 18-kb caprine genomic DNA fragment, comprising the beta-casein transcription unit with about 3-kb 5' and 6-kb 3' flanking regions, was microinjected into fertilized one-cell murine eggs. All nine lines of transgenic mice obtained expressed the transgene in their mammary glands, as demonstrated by Northern blot analysis of mRNA in miscellaneous tissues, and qualitative and quantitative analysis of caprine beta-casein in milk, using SDS/PAGE, Western blotting and rocket immunoelectrophoresis. Two lines produced milk containing up to 21-24 mg of the exogenous protein/ml, a yield which is roughly twice that found in goat milk. The yield reached at least 40 mg/ml in some progeny of crossbred G1 transgenic mice. Thus, the investigated gene appears to be a good candidate for making hybrid constructs that might promote an efficient production of valuable foreign proteins in milk.

Fifty-one patients with carcinoma of the extrahepatic bile ducts (EHBD) received radiation therapy between January 1980 and December 1988. The location of the tumors was: proximal third, 20 patients; middle third, 23 patients; distal third, 3; diffuse, 5 patients. Thirty-six patients underwent surgery with complete gross resection in 14 (10/14 with positive margins), incomplete gross resection in 12 and only biopsy in 10. Fifteen patients had only biliary drainage without laparotomy after cytologic diagnosis of malignancy in 11/15. Radiation therapy was done with curative intent after complete or incomplete resection (n = 26) and it was palliative in patients who had no resection or only biliary drainage (n = 25). Twenty-five patients received external radiation-therapy (ERT) alone to the tumor and lymph nodes (mean dose 45 Gy/2 Gy per fraction for cure, 35 Gy/10 fractions for palliation), 8 patients had only iridium-192 (192Ir) implant (50-60 Gy at a 1 cm radius for cure, 30 Gy for palliation), 17 patients had both ERT + 192Ir (ERT 42.5 Gy + 192Ir 10-15 Gy for cure; ERT 20 Gy/5 fractions + 192Ir 20-30 Gy for palliation) and one intra-operative irradiation + ERT. The overall survival for the entire group was 55, 28.5 and 15% at 12, 24, 36 months and median survival 12 months. Median survival was 22 months in patients treated with curative intent and only 10 months after palliative treatment (p 0.03). Among patients who had curative treatment, median survival was 27.5 months after complete gross resection and 13 months after incomplete gross resection (p 0.045).(ABSTRACT TRUNCATED AT 250 WORDS)

This paper describes the elucidation of the primary structure of the three genetic variants of goat alpha s1-casein, alpha s1-Cn D, E and F, which have been found to be associated with reduced amounts of alpha s1-casein in milk. Variant E has the same electrophoretic mobility as variant B, but differs from the latter by the substitutions of Arg for Lys and of Thr for Ala at positions 100 and 195. A genetically controlled event which does not affect the amino acid sequence of this variant might be responsible for its lower rate of synthesis compared to that of alpha s1-casein B. The deletion of 11 amino acids at positions 59-69 and of 37 amino acids at positions 59-95 in variant B leads to variants D and F. In both cases the deletions, which start at the same position of the polypeptide chain, include the major phosphorylation site of the protein. On the basis of sequence data for casein genes and cDNAs, it was concluded that the deletions occurring in the D and F variants are due to the exclusion of one and several exons, respectively. The observed deletions in the proteins could thus be the consequence of splice site mutations which would induce altered RNA processing and hence reduce the rate of synthesis of the casein.

From January 1986 through December 1988, 227 patients were included in a multi-institutional pilot study for small cell lung cancer (SCLC). Out of the 211 patients who fully completed the staging procedures, 77 (35%) appeared to have SCLC limited to the thorax. All patients received combination therapy consisting of AVI (Adriamycin, VP-16 and Ifosfamide), except during radiotherapy when the Adriamycin was omitted, plus twice daily fractionated 18 MV radiotherapy. Treatment protocol consisted of 4 initial courses of AVI, followed by 3 courses of radiotherapy alternating with modified chemotherapy (VP-16 and Ifosfamide), completed by 2 courses of initial chemotherapy (AVI). Radiotherapy consisted of 1.5 Gy/fraction, 2 fractions/day, 5 days/week in the first course, and 1.8 Gy/fraction, 2 fractions/day, 5 days/week, in the second and third courses, for a total tumor dose of 51 Gy, felt to be equivalent to 60 Gy at normal fractionation. CT treatment planning was employed to design a treatment consisting of multiport radiotherapy, using AP-PA and laterals or obliques beams. During the first course, the homolateral hemithorax received 9 Gy total dose on days 1, 3, 5. During the third course, 360 degrees arctherapy was generally used to boost the reduced tumor volume to a 51 Gy. Besides chest X ray and CT scan, staging and restaging procedures included fiberoptic bronchoscopy. Response rate after irradiation is 61%, with 46% complete responders and 51% local control. The median survival is 14 months, and disease-free survival 42% at 1 year. Complications consisted of cardiac toxicity in 2 patients, 1 death of acute pulmonary toxicity, and 4 instances of moderate chronic radiation pneumonitis. Thus, high doses of radiation can be delivered combined with chemotherapy using this protocol, with an acceptable toxicity and encouraging results in response rate and local control. A longer follow-up is needed to evaluate the impact of these results on survival.

Following the experience of the German authors, the treatment of choroidal melanoma with ruthenium 106 disk was introduced in Lyon. Between 1983 and 1988, 127 patients were treated. Results are analysed on a group of 84 patients followed 18 months and more. In 72 cases a reduction of thickness was noted. It was complete in 33 cases. Enucleation was performed in 10 patients due to no response or regrowth. In 3 cases the tumor was sterilized. Five patients died of metastases, and 73 are alive, 3 of them with liver metastases. An afterloading iridium template disk was used in 8 patients. 4 of them with a tumor thickness between 6.5 and 8 mm had a good response. Edema of the fovea was observed in 21% of cases, while cataracts were very unusual with Ru 106. An enucleation was performed in 6 patients because of a complication. A useful vision may be preserved in 60% of cases. The scleral tolerance dose is close to 1,500 Gy. These results are in agreement with those of the literature and are considered to be satisfactory for tumors not exceeding 5 to 6 mm in thickness. If the tumor is located close to the fovea or the papilla, and/or if the thickness is 8 mm or more, proton beam could be a good alternative.

The association of intraventricular or atrio-ventricular conductive disorders with a calcified aortic stenosis, is a classical notion demonstrated by the close anatomical relationships between aortic valve and conduction pathways. These conductive disorders have been, for quite some time, analyzed on standard electrocardiograms, but, since a few years, the recording of the bundle of His potential has become the technique of choice. However, studies regarding this subject are few, based on very small and sometimes heterogeneous groups of patients. Sixty six consecutive patients hospitalized for a narrow aortic stenosis have agreed to be subjected, before valve replacement, to a recording of the bundle of His potential. Thirteen of them (19.7%) show a HV interval exceeding 55 ms or a pathological H deflexion (twisted and lasting 35 ms). None of the pre-operative parameters that were analyzed (black-out, left ventricular function, ventriculo-aortic gradient, calculated valvular area, magnitude of valvular and ring calcifications), seem correlated with the increased HV interval. These results cross-check those reported in most of the literature.