[Arguments for a role of the gut microbiota in the pathophysiology of hypertension]. / Arguments en faveur d'un rôle du microbiote intestinal dans la physiopathologie de l'hypertension artérielle.

The gut microbiota refers to the community of microorganisms living in the mammalian digestive tract. Over the past decades, numerous preclinical and clinical studies have suggested that gut microbiota is involved in the physiological homeostasis of the host, particularly in the immune and metabolic systems. Furthermore, the dysfunction of gut microbiota, also called "dysbiosis", has been associated with various diseases, such as the metabolic syndrome or chronic kidney disease. In this review, we summarize the knowledge about the possible role of gut microbiota in the development of arterial hypertension. We detail the pathophysiological mechanisms, namely involving short-chain fatty acids produced by the bacterial fermentation of food carbohydrates. These metabolites are reabsorbed by the intestinal mucosa and interact with a multitude of G-protein coupled receptors at the surface of cells involved in blood pressure regulation, including renal tubular cells. These observations open up innovative diagnostic and therapeutic approaches in arterial hypertension, which is a major public health problem.

Le microbiote intestinal désigne la communauté des micro-organismes vivant dans le tube digestif des mammifères. Au cours des dernières années, de nombreuses études précliniques et cliniques ont suggéré que le microbiote intestinal est impliqué dans la régulation physiologique de l'hôte, notamment au niveau des systèmes immunitaires et métaboliques. Bien plus, le dysfonctionnement du microbiote intestinal, également appelé la dysbiose, a été associé à diverses maladies, telles que le syndrome métabolique ou l'insuffisance rénale chronique. Dans la présente revue, nous résumons l'état des connaissances à propos du possible rôle du microbiote intestinal dans le développement de l'hypertension artérielle. Nous en détaillons les mécanismes physiopathologiques impliquant, notamment, les acides gras à chaîne courte produits par la fermentation bactérienne des hydrates de carbone alimentaires. Ces métabolites sont réabsorbés par la muqueuse intestinale et interagissent avec une multitude de récepteurs couplés aux protéines G présents à la surface des cellules impliquées dans la régulation tensionnelle, telles que les cellules tubulaires rénales. Ces observations ouvrent de nouvelles voies diagnostiques et thérapeutiques dans un domaine de santé publique majeur qu'est l'hypertension artérielle.

[Kidney injury in COVID-19]. / Atteintes rénales de la COVID-19.

The SARS-CoV-2 virus causes a respiratory distress syndrome, the main symptom of COVID-19 (for "COronaVIrus Disease 2019"). This infectious disease has been causing a major health and socio-economic pandemic since December 2019. The pulmonary alveolus is regarded as the main target of SARS-CoV-2. However, this coronavirus is capable of directly or indirectly affecting other organs, including the kidneys. Here, we summarize the presumed pathophysiology of COVID-19 renal disease. The incidence of acute kidney injury ranges from 0,5 to 22 % of all patients infected with SARS-CoV-2. The need for renal replacement therapy is reported in 5-9 % of patients in intensive care. Histological analysis of renal biopsies mainly shows acute tubular necrosis of varying severity, as well as the congestion of glomerular and peri-tubular capillaries. Endothelitis has been described in few cases. Evidence for a factual inflammation of the glomerulus remains controversial. The medium/long term consequences of COVID-19 nephropathy are unknown and will deserve a tight follow-up.

Le virus SARS-CoV-2 provoque un syndrome de détresse respiratoire aiguë, le symptôme principal de l'infection COVID-19 (pour «COronaVIrus Disease 2019¼). Cette maladie infectieuse provoque une pandémie de gravité sanitaire et socio-économique majeure depuis décembre 2019. La cible principale du SARS-CoV-2 serait l'alvéole pulmonaire. Néanmoins, ce coronavirus est capable d'affecter directement ou indirectement d'autres organes, y compris les reins. Nous résumons ici la physiopathologie présumée de l'atteinte rénale de la COVID-19. L'incidence de l'insuffisance rénale aiguë varie entre 0,5 à 22 % de tous les patients infectés par le SARS-CoV-2. La nécessité d'une épuration extra-rénale est rapportée chez 5-9 % des patients pris en charge aux soins intensifs. L'analyse histologique de biopsies rénales montre, principalement, une nécrose tubulaire aiguë de sévérité variable, ainsi qu'une congestion des capillaires glomérulaires et péri-tubulaires. Une endothélite a parfois été décrite. L'atteinte inflammatoire du glomérule reste débattue. Les conséquences à moyen/long termes de la néphropathie COVID-19 sont inconnues et mériteront un suivi étroit.

[Acute myocardial infarction due to polycythemia vera]. / Syndrome coronarien aigu lié à une maladie de Vaquez.

We report the clinical case of a patient presenting with an acute myocardial infarction with ST- segment elevation. The patient is affected by polycythemia vera for many years and doesn't have any other cardiovascular risk factors. The frequency of thrombotic events in polycythemia vera (and more particularly myocardial infarction), their predictive factors, pathophysiology and treatment will be discussed.

Nous présentons le cas clinique d'un patient ayant présenté un infarctus aigu du myocarde avec sus-décalage du segment ST dans un contexte de polycythémie vraie (maladie de Vaquez) diagnostiquée plusieurs années auparavant. Le patient ne présente aucun autre facteur de risque cardio-vasculaire. La fréquence des événements thrombotiques (et plus particulièrement des infarctus du myocarde) chez les patients atteints de polycythémie vraie, les facteurs prédictifs de ces derniers, leur physiopathologie et le traitement à proposer seront discutés.

[Management of hypophosphatemia: a case report]. / Le cas clinique du mois. Prise en charge d'une hypophosphatemia.

Hypophosphatemia is defined by a serum phosphate level lower than 0.8 mmol/l. If hypophosphatemia is chronically maintained, it is associated with muscular, osteous, neurological or cardio-respiratory disorders. We describe a patient with isolated hypophosphatemia, detail the mechanisms of phosphate homeostasis, and envisage the differential diagnosis of hypophosphatemia. Furthermore, we propose a sequential decisional algorithm based on basic biological tests and few complementary investigations. Treatment options are reviewed.

Proteomics applied to transfusion plasma: the beginning of the story.

'Safe blood' is and has always been the major concern in transfusion medicine. Plasma can undergo virus inactivation treatments based on physicochemical, photochemical or thermal methodologies for pathogen inactivation. The validation of these treatments is essentially based on clottability assays and clotting factors' titration; however, their impact on plasma proteins at the molecular level has not yet been evaluated. Proteomics appears as particularly adapted to identify, to localize and, consequently, to correlate these modifications to the biological activity change. At the crossroads of biology and analytical sciences, proteomics is the large-scale study of proteins in tissues, physiological fluids or cells at a given moment and in a precise environment. The proteomic strategy is based on a set of methodologies involving separative techniques like mono- and bidimensional gel electrophoresis and chromatography, analytical techniques, especially mass spectrometry, and bioinformatics. Even if plasma has been extensively studied since the very beginning of proteomics, its application to transfusion medicine has just begun. In the first part of this review, we present the principles of proteomics analysis. Then, we propose a state of the art of proteomics applied to plasma analysis. Finally, the use of proteomics for the evaluation of the impact of storage conditions and pathogen inactivation treatments applied to transfusion plasma and for the evaluation of therapeutic protein fractionated is discussed.

[Tuberculous otomastoiditis: advantage of MRI in the treatment survey]. / Otomastoïdite tuberculeuse: intérêt de l'IRM dans le suivi thérapeutique.

PURPOSE: Mycobacterium tuberculosis is a rare cause of otomastoiditis, accounting for less than a percent of chronic otitis media. The diagnosis is difficult and typically delayed because most physicians are unfamiliar with its presenting features and special laboratory requirements. Such delayed diagnosis leads to delayed treatment onset, and thus, increases complications frequency as irreversible hearing loss, facial palsy or meningo-encephalitis complications. Moreover non specific CT findings do not allow any accurate evaluation of inner ear lesions initially and under treatment. CASE REPORT: We described the first case of MRI of tuberculous mastoiditis and the evolution over a 2-years follow-up period. A patient with a clinical history of chronic otorrhea, resistant to conventional therapy, was referred to our department. CT and MRI permitted to describe the initial lesions and to appreciate the medical treatment efficiency (in order to perform surgery in case of failure or complications). Under medical treatment, MRI showed abscess volume decrease at three months while CT was still unchanged. Remineralization only was observed on CT at 12 months. The patient's healing was obtained after 15 months of antituberculous medication. CONCLUSION: MRI has the advantage over CT to demonstrate directly abscess collections that superimposed to areas of bone destructions within the temporal bone. Initially, MRI allows an accurate evaluation of abscess collections and possible meningo-encephalitis complications. Moreover, MRI precises earlier than CT the improvement of lesions and the efficacy of medical treatment, and thus, permitting us to postpone surgery where it is unnecessary.

[Novel criteria for assessing red blood cell viability in blood banks]. / Nouveaux critères d'évaluation de la viabilité des hématies destinées à la transfusion.

UNLABELLED: In light of recent results on the mechanism of programmed cell death of human red blood cells (RBC), the aim of the present study was to solve the enigma of the rapid clearance of transfused RBCs. MATERIALS AND METHODS: We describe new criteria of RBC viability founded on the use of flow cytometry. They were applied, in association with the classical ones: ATP and hemolysis measurements, to RBCs stored in SAGM medium for 42 days. RESULTS AND CONCLUSIONS: Application of an original method of flow cytometric quantitation of in vitro erythrophagocytosis showed that an important proportion of stored RBCs were phagocytized although the following classical signals for phagocytosis were absent, i.e.: desialylation, phosphatidylserine exposure in the outer leaflet of the RBC membrane, loss of CD47 receptor, an antiphagocytosis signal. In addition, ATP was still present and hemolysis was very low. This enigma was solved by the use of scanning electron microscopy, which showed the disappearance of discocytes and the presence of an important proportion of spheroechinocytes, which are the phagocytable forms of RBCs. The mechanism of this dramatic morphological transformation remains to be elucidated.

Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria.

Human mature erythrocytes have been considered as unable to undergo programmed cell death (PCD), due to their lack of mitochondria, nucleus and other organelles, and to the finding that they survive two conditions that induce PCD in vitro in all human nucleated cells, treatment with staurosporine and serum deprivation. Here we report that mature erythrocytes can undergo a rapid self-destruction process sharing several features with apoptosis, including cell shrinkage, plasma membrane microvesiculation, phosphatidylserine externalization, and leading to erythrocyte disintegration, or, in the presence of macrophages, to macrophage ingestion of dying erythrocytes. This regulated form of PCD was induced by Ca(2+) influx, and prevented by cysteine protease inhibitors that allowed erythrocyte survival in vitro and in vivo. The cysteine proteinases involved seem not to be caspases, since (i) proforms of caspase 3, while present in erythrocytes, were not activated during erythrocyte death; (ii) cytochrome c, a critical component of the apoptosome, was lacking; and (iii) cell-free assays did not detect activated effectors of nuclear apoptosis in dying erythrocytes. Our findings provide the first identification that a death program can operate in the absence of mitochondria. They indicate that mature erythrocytes share with all other mammalian cell types the capacity to self-destruct in response to environmental signals, and imply that erythrocyte survival may be modulated by therapeutic intervention.

Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study.

PURPOSE: To improve the results obtained by cystectomy alone and to determine the possibilities of conservative treatment in invasive bladder cancer, we designed a prospective study using a combination of fluorouracil (5-FU) plus cisplatin and concomitant radiation therapy, followed by either cystectomy or additional chemoradiotherapy. PATIENTS AND METHODS: Fifty-four patients with stage T2 to T4 operable untreated invasive bladder cancer were entered onto the study. Treatment was begun in all patients by transurethral resection (TUR) and followed by the 5-FU-cisplatin combination with concomitant bifractionated split-course radiation therapy. A control cystoscopy was performed 6 weeks after completion of the neoadjuvant program. Patients with persistent tumor underwent cystectomy. Complete responders were treated by either additional chemoradiotherapy (group A) or cystectomy (group B). RESULTS: At control cystoscopy, 40 of 54 patients (74%) had a histologically documented complete response. Four responders developed recurrent pelvic disease after a mean follow-up time of 27 +/- 12 months (three in group A and one in group B). Metastatic disease, which developed in 16 patients, occurred more frequently in the nonresponders (71%) than in responders (15%). The disease-free survival rate at 3 years was 62%; it was significantly better in responders (77%) than in nonresponders (23%). There was no difference in survival between groups A and B. CONCLUSION: This neoadjuvant chemoradiotherapy combination, easy to implement and well tolerated even in elderly patients, provides a high complete response rate. It may prove to be effective in inoperable patients and may be proposed as conservative treatment in patients with a complete response to the initial course of chemoradiation.

Two red blood cell units collected in SAG-M additive solution with the ALYX component collection system.

The first protocol available for the new ALYX component system (Baxter Healthcare Inc.) allows automated collection of two Red Blood Cell (RBC) units from one donor. The primary objective of our evaluation was to assess donor safety, comfort and to check the quality of blood products collected. 30 procedures were performed on eligible donors according to French best donation practices. Eligibility criteria were defined in order to ensure a post donation hemoglobin concentration of 11 g/dL minimum. Pre donation ferritin level was also checked. 360 ml of absolute RBC were collected from each donor. Donors physiological parameters and haematological profile were measured immediately before and after donation. Adverse events and donors were observed during the procedure and followed daily during 5 days after donation. Hemolysis in RBC was followed until of shelf life (<0.8% on 42 days storage). The evaluation of different parameters during storage show no difference if we compare with the manual technique. The concentration of hemoglobin is good and all ou concentrates are conform. No serious adverse effects were reported during and after donation. All donors confirmed they would agree to donate 2 RBC units again with this system. We have seen a good quality of RBC products. This evaluation indicates that 2 RBC donation is feasible on the ALYX system, comfortable and safe for eligible donors.

Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review.

Human red blood cells (RBCs) have a life-span of 120 days in circulation, after which they are phagocytized by resident macrophages. Extensive studies have been undertaken by many investigators in order to elucidate the cellular and molecular mechanisms of the erythrophagocytosis. The critical questions addressed by physiologists, clinicians and biochemists are: 'which of the many traumatic blemishes that appear on the erythrocyte surface as it winds its way through the circulation is the primary signal for clearance of the effete RBC from the circulation?', or 'What is the critical signal that it, and it alone, will activate the resident macrophage to adhere to and engulf it?'. Numerous, and often conflicting, hypotheses have been proposed. Each investigator focusing on but one of the many modifications that afflict the cell surface of the ageing erythrocyte, viz changes in either or both the carbohydrate or peptidic moieties of glycoproteins; abolishment of the pre-existing asymmetry in the lipid bilayer with the exposure of phosphatidylserine residues; or alterations in spectrin, to mention but a few. Many of these investigators also have invoked an intermediary role for auto-immune antibodies that recognise the change(s) on the erythrocyte surface and thereby serve as opsonins as a prelude to the erythrophagocytosis. The objective of the present review is to evaluate the data in support of the various hypotheses, and to submit some of our own recent observations involving the use of flow cytometric procedures that: i) provide evidence that the cell surface sialic acid serves as a determinant of the life-span; ii) characterise the senescent erythrocyte population that is specifically captured and phagocytized by macrophages (utilising the rapid and sensitive procedure we developed for quantification of in vitro erythrophagocytosis); and finally iii) provide evidence for the existence of an alternative pathway that is independent of immunoglobulins.

Iridium 192 plesiocurietherapy using silicone elastomer plates for extensive locally recurrent breast cancer following chest wall irradiation.

From July 1985 to October 1988, 11 patients with prior treatment for breast cancer, and presenting an isolated superficial widespread inoperable chest wall recurrence, underwent plesiocurietherapy for salvage. Most patients (91%) had had a mastectomy. The recurrences developed in tissue that had previously been irradiated to 45-55 Gy in three patients and 65 Gy in eight patients. Salvage was attempted using two or three courses of plesiocurietherapy at monthly intervals to decrease treatment complications. The position of the active sources was maintained parallel but slightly shifted at each application. A total dose of 60 Gy was delivered to a Reference Isodose (R.I.) located 2 to 4 mm under the skin surface. The guide system consisted of plastic tubes inserted at 1.5 cm intervals into flexible silicone plates that were applied to the skin surface to maintain the actives lines 0.5 cm above the skin surface. The high dose sleeves surrounding the actives lines (dose greater than 2 x R.I.) were contained within the thickness of the silicone plate. The mean surface treated was 480 cm2 (range 30-1030 cm2). Two patients had continued progression of the lesions within the treated volume during and after curietherapy and died rapidly of metastatic disease. Nine (89%) patients showed complete regression of treated lesions. But two patients developed a new recurrence outside the treated volume. Complications were acceptable: five patients experienced regressive moderate to severe radiation dermatitis and one had skin necrosis that healed in 2 months. These preliminary results have shown that even when tumor extension and previous treatment theorically counter-indicate further local therapy for locally recurrent breast cancer, it is possible to obtain immediate and, at times, lasting control of local disease using two or three courses of plesiocurietherapy with a source shift.

Interstitial iridium 192 for cutaneous carcinoma of the external nose.

Several implantation techniques useful for nasal skin carcinoma have been developed at the Henri Mondor Hospital in Créteil, France and are described in detail. Iridium 192 wires, 0.3 mm in diameter, are afterloaded into either supple plastic tubes or rigid needles implanted according to the rules of the Paris system. Dosimetry is performed by computer, based on either direct measurements of active lengths and spacing, orthogonal films or a tomogram oriented in the central plane of the implant. According to a recent review by the European Curietherapy Group of 468 implants, the optimal dose is 60 Gy. The overall failure rate was 2.6%. Indications for implantation and choice of technique, based on tumor size, site, and gross morphology are discussed.

Salvage irradiation of oropharyngeal cancers using iridium 192 wire implants: 5-year results of 70 cases.

Between May 1971 and November 1980, 70 patients with recurrent or new oropharyngeal cancers arising in previously irradiated tissues were treated using iridium 192 afterloading techniques. The actuarial local control was 72% at 2 years and 69% at 5 years. Although local control of the tumor was achieved in the majority of these patients, only 10 patients remained alive at 5 years (14%). Patients with lesions of the faucial arch and posterior pharyngeal wall had the best results; local control was achieved in 100% of these patients. Patients with lesions of the base of tongue and of the glosso-tonsillar sulcus had poorer results; local control was achieved in 61%. Because these results compare favorably with the results of previously published series, we recommend re-irradiation with brachytherapy for recurrent or new malignancies arising in a previously irradiated oropharynx. When the lesion is located in the faucial arch, brachytherapy is the treatment of choice. When the lesion is located in the base of tongue, brachytherapy is a reasonable option.

Interstitial radiation therapy for squamous cell carcinoma of the tonsillar region: the Creteil experience (1971-1981).

From July 1971 to December 1981, 33 selected patients with T1, T2 tumors of the tonsillar region were treated according to the following protocol: 1. Telecobalt therapy to the primary site and to neck nodes to a dose of 45 Gy. 2. Brachytherapy to the primary site to a dose of 30 Gy using iridium 192. 3. Boost dose to involved neck nodes with electrons, or radical neck dissection, whether N1, N2, or N3. The actuarial disease-free survival was 76% when all patient groups were included and 80% for the N0 patients. The local control rate was 100%. Disease control in the neck was 94% overall and 100% for the N0 group. These results favor the use of this protocol for superficial, minimally infiltrating tumors less than 4 cm in diameter, without obvious extension to the base of the tongue or retromolar trigone.

Split course interstitial brachytherapy with a source shift: the results of a new technique for salvage irradiation in recurrent inoperable cervical lymphadenopathy greater than or equal to 4 cm diameter in 23 patients.

Between June 1981 and December 1986, 23 patients with prior irradiation of the neck for epithelial ENT tumors underwent salvage irradiation for isolated recurrent inoperable cervical lymphadenopathy greater than or equal to 4 cm. The initial irradiation had delivered 45-80 Gy to the cervical lymph nodes. Split course interstitial brachytherapy was used with a source shift in an attempt to decrease treatment complications. The first and second course of the split course implants delivered 35 Gy and 30 Gy at a 1 month interval. The active lines of the second implant were placed parallel to and in between the position of the lines of the first implant. Three patients did not receive the second implant (one death, one disease evolution, one necrosis). For the patient who died between the first and second implants the local control rate could not be determined. The immediate overall local control rate was 73% (16/22) with a later recurrence rate of 62% (10/16), but only in three cases was recurrence within the treated volume (19%-3/16). The local control rate was better (3/9) if the initial lymphadenopathy was greater than or equal to 4 cm less than or equal to 6 cm but worse (3/13) in those with initial lymphadenopathy greater than 6 cm. Survival of these patients overall was poor with 26% survival at 1 year and 13% at 2 years. Tolerance overall was acceptable with tissue necrosis occurring in 36.5% of cases including those with initial skin involvement. If these cases were excluded the necrosis rate was only 15.5%. In this patient population with inoperable recurrent cervical lymphadenopathy in whom a further dose of external irradiation is not possible interstitial brachytherapy should be considered. Our technique of implantation, split over two sessions with a source shift, is practicable with an acceptable toxicity. It may be used even after high dose external beam irradiation and in large volumes of disease, and it gives better results than classical brachytherapy.

Split course interstitial brachytherapy with a source shift: the results of a new iridium implant technique versus single course implants for salvage irradiation of base of tongue cancers in 55 patients.

Between January 1973 and December 1984, 55 patients with prior irradiation of the oropharynx underwent salvage irradiation for recurrent (26 patients) or second cancers (29 patients) of the base of tongue. The initial irradiation had delivered from 45 to 80 Gy to the base of tongue. One of two techniques of Iridium implantation was used for salvage. Single course implants, delivering 60 Gy, were used until June 1981 in a total of 31 patients. After June 1981, split course implants with a source shift were used in 24 patients in the hope of decreasing treatment complications. The first and second course of the split course implants delivered 35 and 30 Gy, respectively, at a 1-month interval. The active lines of the second implant were placed parallel to and between the position of the lines of the first implant. This shift in the source position resulted in a more uniform dose within the treated volume with a 60% reduction in the high dose sleeves. The overall 3-year survival was 19% (28% T less than or equal to 3 cm). The overall local failure rate was 45.5% (25/55). The difference between the local failure rate after single course implants (52%) and after split course implants (37.5%) was not statistically significative. The response observed after the first course of a split course implant proved to be a reliable indication of the probability of achieving local control after a full course of treatment: 2/14 failures (14%) if the response was greater than or equal to 75% versus 7/10 (70%) if the response was less than 75% (p less than 0.01). The only complication noted in the 40 patients achieving immediate local control after either implant technique was mucosal necrosis. The introduction of split course implants was followed by a two and a half fold decrease in the incidence of necrosis: 43% (9/21) in the single course group and 16% (3/19) in the split course group (p = 0.05). Interstitial brachytherapy offers an effective and reasonable option for salvage therapy in patients with recurrent and second cancers occurring in the base of tongue even when the tumor arises in a zone that has previously received high dose irradiation. The use of split course implants with a shift in the position of the active lines at the time of the second implant significantly decreases the risk of radionecrosis.

Single-fraction stereotactic radiotherapy: a dose-response analysis of arteriovenous malformation obliteration.

PURPOSE: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. METHODS AND MATERIALS: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 +/- 230 mm3 (median 968 mm3; range 62-11, 250 mm3). The mean minimum target dose (Dmin) was 19 +/- 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 +/- 300 mm3 (median 1200 mm3; range 75-14 900 mm3). The mean maximum dose (Dmax) was 34.5 +/- 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 +/- 2.3 months (median 37.5; range 7-117). RESULTS: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 +/- 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), Dmin by steps of 5 Gy (p = 0.005), targeted volume of the nidus (< or = 968 mm3 vs. >968 mm3; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the Dmin [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p = 0.010). Delayed complications were observed in eight patients. The 5-year actuarial rate of delayed complications was 7.4%. CONCLUSION: After stereotactic radiotherapy delivered in a single high dose using a single-isocenter technique, the success rate for complete obliteration is independently correlated to Dmin but does not seem to be influenced by Dmax and the targeted volume of the nidus.

Interstitial radiation therapy for carcinoma of the penis using iridium 192 wires: the Henri Mondor experience (1970-1979).

From 1970 to 1979, a group of 50 patients was treated for squamous cell carcinoma of the penis by interstitial irradiation using an afterloading technique and iridium 192 wires. The group included 9 patients with T1 tumors, 27 with T2 tumors, and 14 with T3 tumors. Forty-five patients presented with no metastatic inguinal nodes (N0), 3 patients with N1 nodes, and 2 patients had N3 nodes. After treatment, 11 patients (1 T1, 6 T2 and 4T3) developed local recurrences; 10 of these 11 patients underwent penile amputation which controlled the tumor in 7 of the patients. One patient refused amputation. Three patients developed post-therapeutic necrosis which necessitated partial amputation in 2 cases. Eight patients developed post-therapeutic urethral stenosis, which required surgical treatment in three of the cases. Overall, at their last follow-up examinations, 74% of the patients were free of disease with conservation of penile morphology and function. Most patients without metastatic nodes (37/45) at diagnosis did not receive prophylatic treatment of the groin. Two of these patients developed delayed metastatic nodes; one was successfully salvaged. All 5 patients presenting with metastatic nodes at diagnosis died, four with uncontrolled regional disease. Twenty-one percent of the patients died of their disease. We advocate interstitial irradiation using iridium 192 wires for the treatment of non-infiltrating or moderately infiltrating squamous cell carcinoma of the penis in which the largest dimension does not exceed 4 cm. Pre-implant circumcision and regular long-term follow-up are necessary. More extensive tumors are better managed surgically. When regular follow-up can be assured, it is reasonable to forgo prophylactic treatment of the inguinal nodes in patients presenting without groin metastasis.

Adenocarcinoma of the endometrium treated with combined irradiation and surgery: study of 437 patients.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. METHODS AND MATERIALS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). CONCLUSION: Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.