The American Board Diplomate.
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Biomedical subjects
Publications and source records attributed to C Berger.
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PURPOSE: A retrospective analysis of conservative treatment of anal canal cancers with external radiation therapy and interstitial brachytherapy with or without chemotherapy. PATIENTS AND METHODS: From 1986 to 1996, 69 patients were treated with external radiotherapy (40 Gy/20 fractions) and interstitial brachytherapy (20 Gy) after a mean interval of six weeks for a localized epidermoid carcinoma of the anal canal. Patients who did not complete the whole therapeutic sequence were not included. Forty-five patients received additional 5-fluorouracil- and/or mitomycin C-based chemotherapy regimen. RESULTS: Acute toxicity was acceptable. Complete response rate was 81%. Actuarial local control rate was at two and five years, 65% and 59% respectively (median follow-up: eight years). At two, five and ten years, actuarial colostomy rate was 26%, 33% and 33% respectively, and colostomy-free survival rates 61%, 47% and 37%. Overall survival at two, five and ten years was 81%, 65% and 53% respectively. Distant metastases occurred in 11 patients (16%). Prognostic factors for overall survival were performance status (PS) (79% survival at five years for patients with PS 0 versus 50% for patients with PS 1-3, P = 0.04) and tumor stage (80% at five years for T1-T2 versus 53% for T3-T4, P = 0.03). Overall treatment time less than 12 weeks and time interval between external radiotherapy and brachytherapy inferior than six weeks were associated with a better local control (P = 0.05). In multivariate analysis, these prognostic factors were not significant. CONCLUSION: These results confirm the efficacy of external radiotherapy and brachytherapy in the treatment of small anal canal cancers, and point out the need for improving treatment outcome of larger tumors.
The aim of three-dimensional conformal therapy (3DCRT) is to treat the Planning Target Volume (PTV) to the prescribed dose while reducing doses to normal tissues and critical structures, in order to increase local control and reduce toxicity. The evaluation tools used for optimizing treatment techniques are three-dimensional visualization of dose distributions, dose-volume histograms, tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). These tools, however, do not fully quantify the conformity of dose distributions to the PTV. Specific tools were introduced to measure this conformity for a given dose level. We have extended those definitions to different dose levels, using a conformity index (CI). CI is based on the relative volumes of PTV and outside the PTV receiving more than a given dose. This parameter has been evaluated by a clinical study including 82 patients treated for lung cancer and 82 patients treated for prostate cancer. The CI was low for lung dosimetric studies (0.35 at the prescribed dose 66 Gy) due to build-up around the GTV and to spinal cord sparing. For prostate dosimetric studies, the CI was higher (0.57 at the prescribed dose 70 Gy). The CI has been used to compare treatment plans for lung 3DCRT (2 vs 3 beams) and prostate 3DCRT (4 vs 7 beams). The variation of CI with dose can be used to optimize dose prescription.
PURPOSE: To evaluate retrospectively treatment-related morbidity of concurrent radiotherapy and chemotherapy for rectal cancer. PATIENTS AND METHODS: Between 1992 and 1995, 38 patients (median age: 60) were treated for locally advanced resectable rectal cancer. Median dose of radiotherapy was 45 Gy/25 fractions/5 weeks. Chemotherapy consisted of two courses of 5-fluorouracil and leucovorin administered during the first and the fifth weeks of radiotherapy. Median dose of 5-fluorouracil was 350 mg/m2/day, and median dose of leucovorin was 20 mg/m2/day, day 1 to day 5. Surgery was performed 5 weeks after completion of radiotherapy. RESULTS: Before surgery, one patient died of febrile neutropenia and sepsis after two cycles of chemotherapy and 45 Gy. Main pre-operative grade 3-4 toxicities were respectively: neutropenia: 3%; nausea/vomiting: 3%; diarrhea: 3%; proctitis: 5%; radiation dermatitis: 8%. Twenty-six patients underwent a low anterior resection and 11 an abdomino-perineal resection. A temporary colostomy was performed in 12 patients. Pathologic complete response rate was 27%. There was one post-operative death due to thromboembolic disease. Major post-operative grade 3-4 complications were: pelvic infection: 14%; abdominal infection: 5%; perineal sepsis: 8%; anastomotic dehiscence: 8%; cardiac failure: 5%. Delayed perineal wound healing was observed in six patients. No significant prognosic factor of post-operative complications has been observed. Median duration of hospitalization was 22 days. With a median follow-up of 24 months, 2-year overall and disease-free survival rates were 82 and 64%. CONCLUSION: Tolerance of preoperative concurrent chemoradiotherapy was acceptable. Ongoing controlled studies will assess the impact of this combined treatment on survival.
Therapeutic strategies for muscle invasive bladder cancer are currently evolving. Transurethral surgery followed by concurrent chemotherapy and radiotherapy is the best treatment for patients not suitable for radical cystectomy. This conservative approach may be proposed for operable patients with similar survival than after cystectomy. Intermediate evaluation of response is necessary, as response is the more discriminant prognostic factor for local control. Non responders would be assigned for immediate cystectomy. Morbidity and results of salvage cystectomy are poorly evaluated and probably depending from time from initial treatment and dose of radiation.
Accuracy of conformal treatment planning for prostatic radiotherapy is based on the contours of target volumes (prostate +/- seminal vesicles) and normal tissues (rectum and bladder), drawn on CT (computed tomography) images by radiation oncologists. The interpretation of a given CT image can be different from one radiation oncologist to another, and may change in time with the state of filling of the bladder and of the rectum during the treatment. In order to quantify these variations, 12 patients treated with conformal radiotherapy for prostate carcinoma (pelvis 40 Gy/20 sessions + prostate 30 Gy/15 sessions) had two series of CT at one month intervals. Contouring of prostate, rectum and bladder were performed independently on each CT by two radiation oncologists. The first CT scan (planning CT) and the first series of contours (planning contours) were used for treatment planning. The contours of the second scan were compared to the planning contours after image fusion based on manual superimposition of bony anatomy of the two sets of CT images. Coherence ratio were defined to measure discrepancies in prostate volumes between radiation oncologists (RCE) and between scans (RCT). The mean RCE was 38 +/- 7% (1 standard deviation). Those discrepancies were primarily located at the prostate apex and at the interface between bladder and prostate and between rectum and prostate. The mean RCT was 42 +/- 8% (1 sigma). Those discrepancies were due to the prostate motion related to the state of filling of the rectum and bladder. For bladder and rectal walls, less important differences were observed between the two radiation oncologists for the same CT (4.5% for rectal volume receiving 65 Gy or more, 3% for bladder volume receiving 65 Gy or more). However, important differences in bladder and rectal volumes receiving 65 Gy or more (16% and 7% respectively) were noted for the same patient from a CT to another due to the variation in bladder or rectal filling. New techniques for planning CT acquisition are needed to decrease the discrepancies due to contouring. The treatment must, as far as possible, be delivered with an empty bladder and rectum in order to ensure a good reproduction of the initially planned treatment.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus with worldwide distribution. Primary infection with EBV occurs early in life and typically presents as infectious mononucleosis. The usual course of the disease is benign and most patients recover uneventfully. Severe infections are reported particularly in immunocompromised patients. Mild, asymptomatic pneumonitis is reported in about 5-10% of cases of infectious mononucleosis, but severe pneumonitis with hypoxemia is very rare in immunocompetent individuals. We report a young female adolescent in whom an acute EBV infection led to severe bilateral pneumonitis, a systemic inflammatory response and intracerebral bleeding. The clinical course and results of quantitative viral DNA determinations in plasma are presented.
Serum and cerebrospinal fluid (CSF) from 44 patients with clinical probable Alzheimer's disease (AD) (subdivided in two groups with 18 early onset, EO, and 26 late onset, LO, cases), 10 patients with vascular dementia (VD) and 24 patients with major depression (MD) were assayed for concentrations of albumin and IgG. The severity of dementia was assessed with the Mini Mental State Examination. The CSF/serum ratio for albumin and IgG as well as the IgG index were used to evaluate blood-CSF barrier function. Various patients showed signs of blood-CSF-barrier (BCB) dysfunction and only few displayed evidence of local IgG synthesis in the central nervous system (CNS) in the AD, VD and in the MD group (IgG index > 0.7). The permeability of the blood-CSF barrier was not correlated to measures of dementia severity. Our data support the hypothesis of a BCB leakage in a subgroup of all investigated patients. Furthermore, we found a small number of patients with increased intrathecal IgG synthesis. Elevated CSF immunoglobulins combined with BCB impairment might be associated or caused by a general immune activation. Our data are in agreement with the assumption that an inflammatory process may play a role in a subgroup of patients with AD but also with MD and less likely in VD. In conclusion BCB impairment and elevated IgG immunoglobulin levels are unspecific either for AD, VD or MD.
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Although cyclosporine has helped make heart transplantation a clinical reality, long-term survival remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic heart transplants despite cyclosporine administration. The hypothesis of the present study is that cyclosporine-treated human heart transplant recipients are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 240 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with serum panel reactive antibody levels greater than 10% were considered antibody producers, whereas those with serum panel reactive antibody levels less than 10% were considered nonproducers. To establish the time course of post-transplantation sensitization, we have tested anti-HLA antibodies in sequential sera at 3-month intervals after transplantation. The 4-year actuarial survival rate of those patients whose panel reactive antibody levels were greater than 10% during the first 6 months after transplantation was 70%, whereas the survival rate of patients whose levels were less than 10% during this time was 93%. The results were significantly different (p less than 0.01). Further heterogeneity among the patients was demonstrated by differential analysis of survival in patients who showed (1) panel reactive antibody levels less than 10% in any of the sera obtained during the first year after transplantation, (2) panel reactive antibody levels greater than 10% in sera obtained during the first 6 months but not thereafter, and (3) panel reactive antibody levels greater than 10% throughout the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate drug utilization during the last 15 days of pregnancy, one hundred six women were interviewed post-delivery in the CHU Bretonneau in Tours. Eighty-three percent received at least one drug during the 15 days preceding delivery and 27% more than 3 different drugs. Treatments for venous disorders (31% of patients), iron (31%), analgesics (25%), antacids (11%), magnesium (11%) and laxatives (11%) were most frequently used. In 92% of cases the drug was prescribed. Five women received a drug with potential risk for the neonate. However only one infant developed and adverse effect, possibly due to benzodiazepine (hypotonia).
The study of a population of 79 obese people (62 women and 17 men) allowed to find out, and to specify a certain number of data shown through questionning, clinical examination and biological observations: the predominance of female application for weight regression treatments; the much more important number of major overweight with men; the idea of a "certain" age after which the micrease in weight is less important; the relation between the weigth after birth and overweight; the relation between how long you been futting on weight and the importance of your overweight; the frequency of overweight among your relatives. As for as spontaneous nutrition is concerned the frequency of normal food intake or even of hypocaloric intake, the immoderate proportion of fat intake and the frequency of the few, daily meals. As far as the biological aspect is concerned, the frequency of chemical diabetes and the possibility to distinguish from the oral glucose tolerance test together with the proportion of insulinemy, four groups of subjects ranging from the state of normal sugar regulation to proved diabetes, the frequency of hyperlipemy and hypercholesterolemy; the little difference between the free fat acids in the plasma, or an empty stomach as well as during the oral glucose tolerance test, with regard to normal subjects, with nevertheless, an important relation between the importance of the overweight and the average of fat acids.
The authors studied two series of deaths (437 cases in all), one from a prospective study on the Centre region and the other from a retrospective study on the Tourangelle region; they compared the clinical and paraclinical data recorded during pregnancy, labour and the neonatal period to the autopsy results and those of the different tissue examinations, and strived to define the most judicious indications for autopsies in case of perinatal death. From their conclusions, based on the clinical context of the death, 5 different types of situations can be distinguished: for two of them, namely the medico-legal context and the malformation context, the post mortem examination seems indispensable for different reasons. In case of "obvious clinical diagnosis", the need for an autopsy has not been proven. However, when the clinical diagnosis seems "probable" or when the aetiology has not been found clinically, the post mortem examination of the foetal body is recommended, although certain particular situations, related to the age of the mother, the parity, the interest shown by the couple about the result, to ethnic or religious factors, may lead to the request of only a limited examination, which is much less expensive.
A study of 79 obese patients who were hospitalized and treated with a low calorie diet demonstrated that the weight loss occurred in a univocal manner, according to a semilogarithmic law. It was not influenced, as far as initial results were concerned, by the age, sex, or morphotype of the patient, or whether weight gain was recent or of long-standing. Factors affecting results, however, are the existence of functional signs, the amount of natriuresis during the first few days, and the quantity of alcohol ingested regularly. Short term results, one month after leaving hospital, appear to be moderate only. A diet supplying 800 calories causes weight loss at the expense of body fat. Individual variations in minimal calorie requirements during the treatment can be used as a basis for prescribing a personalized supplementary diet.
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