BRCA1 haplotype and clinical benefit of trabectedin in soft-tissue sarcoma patients.

BACKGROUND: This study aimed to determine whether the BRCA1 haplotype was associated with trabectedin efficacy in soft-tissue sarcoma (STS) patients. METHODS: We analysed BRCA1 single-nucleotide polymorphisms (SNPs) in tumour specimens from 135 advanced STS patients enrolled in published phase 2 trials or in a compassionate-use programme of trabectedin. Forty-four advanced STS patients treated with doxorubicin and 85 patients with localised STS served as controls. The 6-month nonprogression rate and overall survival (OS) were analysed according to BRCA1 haplotype using log-rank tests. RESULTS: A favourable BRCA1 haplotype (presence of at least one AAAG allele) was significantly associated with an improved 6-month nonprogression rate. It was the only variable significantly associated with OS. No correlations were found between outcomes for patients with localised or advanced STS treated with doxorubicin. CONCLUSIONS: The BRCA1 haplotype represents a potential DNA repair biomarker that can be used for the prediction of response to trabectedin in STS patients.

Retroperitoneal sarcomas: patterns of care at diagnosis, prognostic factors and focus on main histological subtypes: a multicenter analysis of the French Sarcoma Group.

BACKGROUND: Retroperitoneal sarcomas (RPS) are heterogeneous. No previous study has investigated the impact of specialized surgery, evaluated locoregional relapse (LRR), abdominal sarcomatosis and distant metastatic relapse as separate events, or considered histological subtypes separately. This study addresses these specific points in a homogeneous cohort of patients with completely resected primary RPS. PATIENTS AND METHODS: We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 and eventually referred to one of 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS: Five hundred eighty-six patients were included. Median follow-up was 6.5 years [95% confidence interval (CI) 5.9-7.1]. Five hundred thirty-seven patients had localized disease and 389 patients (76%) had macroscopically complete resection of the tumor. In this latter group, the 5-year LRR-free survival rate was 46% [41-52] and the 5-year overall survival (OS) rate was 66% [61-71]. In multivariate analysis, gender, adjacent organ involvement, specialization of the surgeon, piecemeal resection and perioperative radiotherapy were independently associated with LRR. Specialization of the surgeon and piecemeal resection were independently associated with abdominal sarcomatosis whereas histology and adjacent organ involvement were independently associated with distant metastasis. Age, gender, grade, adjacent organ involvement and piecemeal resection were significantly associated with OS. Prognostic factors for LRR and OS were analyzed in well-differentiated and dedifferentiated liposarcomas and leiomyosarcomas. Grade 3 was an independent prognostic factor for OS of dedifferentiated liposarcomas. CONCLUSION: This study underlines the crucial role of pretherapeutic assessment and meticulous histological examination of RPS as well as the need to consider histological subtypes separately. Surgery in a specialized center and avoidance of piecemeal resection stand out as the two most important prognostic factors for RPS and highlight the importance of treating these patients in specialized centers.

Response to chemotherapy is not related to chromosome instability in synovial sarcoma.

BACKGROUND: Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy. PATIENTS AND METHODS: The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen. RESULTS: Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity. CONCLUSION: The absence of significant association between response to chemotherapy and genomic complexity suggests that the prognostic value of chromosome instability in SS is independent of response to chemotherapy; mechanisms leading to metastatic relapse of SS are intrinsic to the biology of the tumor and current cytotoxic drugs are only poorly efficient to prevent it.

Retroperitoneal sarcomas: patterns of care in advanced stages, prognostic factors and focus on main histological subtypes: a multicenter analysis of the French Sarcoma Group.

BACKGROUND: Retroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately. PATIENTS AND METHODS: We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS: Five-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0-8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9-7.3] and median overall survival (OS), 15.8 months [13-18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit. CONCLUSION: These results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.

Interest of diffusion-weighted and gadolinium-enhanced dynamic MR sequences for the diagnosis of parotid gland tumors.

PURPOSE: This study aimed to evaluate the value of diffusion-weighted imaging (DWI) and gadolinium-enhanced dynamic magnetic resonance imaging (MRI) for differentiating benign and malignant parotid gland tumors, and for characterizing the various histological types (pleomorphic adenoma, and Warthin's and malignant tumors). PATIENTS AND METHODS: This retrospective study involved 60 patients with suspected parotid gland tumors (mean age: 59.4 years), and was carried out from April 2005 to February 2008. All had undergone pathological examination. All MRI examinations were performed using the Siemens Magnetom Avanto 1.5T MRI system. Non-enhanced T1-weighted (T1W), gadolinium-enhanced fat-suppressed T1W and T2-weighted (T2W) images were obtained for all 60 patients, with diffusion-weighted echoplanar imaging (DW-EPI) and apparent diffusion coefficient (ADC) evaluation in 59 patients, and gadolinium-enhanced dynamic MRI sequences in 51 patients. Interpretation was carried out by two experienced radiologists (the first evaluation used T1W, gadolinium-enhanced fat-suppressed T1W and T2W images; the second evaluation used T1W, T2W, DWI and dynamic MRI) and, for each case, the benign/malignant nature of the tumor and its histological type were determined. RESULTS: After the second reading, increases were noted in sensitivity, specificity, malignant positive predictive value (PPV) and negative predictive value (NPV), as well as in accuracy (90-100% for the first observer, and 90-97% for the second observer). Interobserver reliability also showed a significant increase from the first to the second reading (kappa=0.63 to 0.87, respectively). CONCLUSION: Gadolinium-enhanced dynamic MRI and DW-EPI with ADC evaluation improved the performance of MRI in distinguishing between benign and malignant parotid gland tumors, and characterizing the different histological types of benign tumors (pleomorphic adenoma and Warthin's), thus leading to greater consensus in interpretation of the images.

High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.

BACKGROUND: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome. METHODS: Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). RESULTS: Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). CONCLUSION: A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

Detection of K-Ras mutations in tumour samples of patients with non-small cell lung cancer using PNA-mediated PCR clamping.

Non-small cell lung cancers (NSCLC), in particular adenocarcinoma, are often mixed with normal cells. Therefore, low sensitivity of direct sequencing used for K-Ras mutation analysis could be inadequate in some cases. Our study focused on the possibility to increase the detection of K-Ras mutations in cases of low tumour cellularity. Besides direct sequencing, we used wild-type hybridisation probes and peptide-nucleic-acid (PNA)-mediated PCR clamping to detect mutations at codons 12 and 13, in 114 routine consecutive NSCLC frozen surgical tumours untreated by targeted drugs. The sensitivity of the analysis without or with PNA was 10 and 1% of tumour DNA, respectively. Direct sequencing revealed K-Ras mutations in 11 out of 114 tumours (10%). Using PNA-mediated PCR clamping, 10 additional cases of K-Ras mutations were detected (21 out of 114, 18%, P<0.005), among which five in samples with low tumour cellularity. In adenocarcinoma, K-Ras mutation frequency increased from 7 out of 55 (13%) by direct sequencing to 15 out of 55 (27%) by clamped-PCR (P<0.005). K-Ras mutations detected by these sensitive techniques lost its prognostic value. In conclusion, a rapid and sensitive PCR-clamping test avoiding macro or micro dissection could be proposed in routine analysis especially for NSCLC samples with low percentage of tumour cells such as bronchial biopsies or after neoadjuvant chemotherapy.

EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up.

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib improves survival of lung cancer as second- or third-line therapy. However, after an initial response, most patients will recur, particularly within the central nervous system. The present study reports the case of a 27-yr-old nonsmoking male presenting with a metastatic lung adenocarcinoma with EGFR exon 19 deletion, associated with sensitivity to EGFR-TKI. Gefitinib, followed by chemotherapy and finally erlotinib resulted in prolonged disease control, until multiple liver metastases were detected. After stopping EGFR-TKI, brain metastases with carcinomatous meningitis were diagnosed. A secondary T790M mutation, associated with resistance to EGFR-TKI, was found on the liver biopsy but not in the cerebrospinal fluid. Erlotinib was reintroduced and allowed a quick neurological improvement, even though the extra-cranial disease remained resistant to erlotinib. The present report underscores the interest of molecular monitoring in lung cancer. Persistent cerebral tyrosine kinase inhibitor sensitivity should be considered in patients presenting with an early central nervous system relapse after stopping epidermal growth factor receptor tyrosine kinase inhibitor, even with a T790M-resistant mutation in noncerebral metastases. Questions remain concerning the selection of sub-clones during epidermal growth factor receptor tyrosine kinase inhibitor therapy, which could differ according to metastatic sites, especially in the central nervous system.

Type 1 diabetes and idiopathic retroperitoneal fibrosis: case report.

Retroperitoneal fibrosis is characterized by the presence of a retroperitoneal tissue, consisting of chronic inflammation and marked fibrosis, which entraps the retroperitoneal organs. In two-thirds of cases, the retroperitoneal fibrosis is idiopathic. The pathogenic mechanism is not clearly identified. We report a case of idiopathic retroperitoneal fibrosis associated with type 1 diabetes mellitus. A 61-year-old woman with C peptide negative insulindependent diabetes developed retroperitoneal fibrosis revealed by bilateral hydronephrosis. Anti-GAD 65 antibodies were positive. There were no signs of autoimmune pancreatitis: no steatorrhea, normal IgG4 isotype levels, and absence of pancreas morphological abnormalities.

Chimeric smooth muscle-specific enhancer/promoters: valuable tools for adenovirus-mediated cardiovascular gene therapy.

Gene transfer with adenoviral vectors is an attractive approach for the treatment of atherosclerosis and restenosis. However, because expression of a therapeutic gene in nontarget tissues may have deleterious effects, artery-specific expression is desirable. Although expression vectors containing transcriptional regulatory elements of genes expressed solely in smooth muscle cells (SMCs) have proved efficient to restrict expression of the transgene, their use in the clinical setting can be limited by their reduced strength. In the present study, we show that low levels of transgene expression are obtained with the smooth muscle (SM)-specific SM22alpha promoter compared with the viral cytomegalovirus (CMV) enhancer/promoter. We have generated chimeric transcriptional cassettes containing either a SM (SM-myosin heavy chain) or a skeletal muscle (creatine kinase) enhancer combined with the SM22alpha promoter. With both constructs we observed significantly stronger expression that remains SM-specific. In vivo, reporter gene expression was restricted to arterial SMCs with no detectable signal at remote sites. Moreover, when interferon-gamma expression was driven by one of these two chimeras, SMC growth was inhibited as efficiently as with the CMV promoter. Finally, we demonstrate that neointima formation in the rat carotid balloon injury model was reduced to the same extent by adenoviral gene transfer of interferon-gamma driven either by the SM-myosin heavy chain enhancer/SM22alpha promoter or the CMV promoter. These results indicate that such vectors can be useful for the treatment of hyperproliferative vascular disorders.

[Primary meningeal intermediate grade melanocytic neoplasm: case report with radiologic-pathologic correlation]. / Tumeur mélanocytaire méningée primitive de grade intermediaire: confrontation radio-pathologique.

A case of primary meningeal intermediate grade melanocytic neoplasm involving the right C2 nerve root is presented. MRI findings may suggest this rare entity, especially when an extra-axial lesion is located in the posterior fossa or cervical spinal canal and demonstrates shortening of both T1 and T2. Eventually, definitive diagnosis relies on histology which demonstrates spindle-shaped melanocytic cells that are Fontana stained and positive for HMB:45 antigen. Cellularity, pleomorphism, mitotic rate, proliferation index and invasiveness are useful criteria to distinguish among the spectrum of primary melanocytic tumors of the central nervous system ranging from melanocytoma to malignant melanoma.

Hepar lobatum carcinomatosum associated with liver metastases from breast cancer: report of five cases.

BACKGROUNDS AND AIMS: Hepar lobatum carcinomatosum (HLC) is an exceptional acquired hepatic distortion which consists in irregularly lobulated hepatic contours seen in patients with known liver metastases, usually from breast carcinoma. We aimed to describe and analyze five similar cases of HLC resulting from metastatic mammary carcinoma in the liver and associated with rapid hepatic failure. METHODS: Five cases of HLC were investigated. Medical (including blood liver tests), radiological and histological data (2 cases) were collected and retrospectively analyzed. All patients were followed up for metastatic invasive ductal carcinoma of the breast and had a common pattern of treatment with combination of targeted therapies (bevacizumab, AVASTIN) and chemotherapy (paclitaxel, TAXOL). RESULTS: All the patients showed rapid hepatic failure after a mean of 9 courses of bevacizumab/paclitaxel. In all cases, liver imaging revealed liver capsule retraction and an irregular lobular margin. An apparent tumor regression of all liver metastases was showed in two cases. Biopsies were consistent with sinusoidal obstruction syndrome (SOS) and, surprisingly, no tumoral cells were found. CONCLUSION: Although rare, such an unusual pattern of liver metastasis may mimick acute cirrhosis and cause rapid hepatic failure in patients, despite possible apparent tumor regression on imaging. The etiology of this pathology is unclear, and may involve multiple pathogenic factors. Direct or indirect vascular injury plays an important role in the development of HLC.

Influence of VEGF on the viability of encapsulated pancreatic rat islets after transplantation in diabetic mice.

After pancreatic islet transplantation, insufficient blood supply is responsible for the loss of islet viability. The aim of our study was: 1) to determine the influence of vascular endothelial growth factor (VEGF) on the survival of encapsulated rat islets transplanted into healthy and diabetic mice and 2) to evaluate the metabolic efficiency of the VEGF-supplemented grafts. Twenty-four hours after culture, 50 rat islets immobilized into collagen in the presence of VEGF (100 ng/ml) and encapsulated (AN69 membrane, HOSPAL) were grafted in the peritoneal cavity of healthy or streptozotocin-induced diabetic mice (n = 6). Seven, 14, and 28 days after implantation, the encapsulation device and tissue surrounding the device were removed and the following parameters were analyzed: the number and the diameter of buds, the distance between devices and buds, the amount of cellular adhesion on the capsule surface, and the level of insulin secreted by encapsulated islet. For reversal of diabetes, 1000 rat islets encapsulated in the presence of VEGF were implanted in the peritoneal cavity of diabetic mice and fasting glycemia was analyzed. After 7 days of islet implantation in the absence of VEGF, the bud diameter was 16.1 +/- 6.9 microm in diabetic mice and 34.4 +/- 3.9 microm in healthy mice. However, the number of buds increased by a factor 2.5 in the presence of VEGF in both types of mice. Furthermore, when islets were transplanted in the presence of VEGF, the distance between the device and the buds was significantly decreased in both types of mice (p < 0.001) after 7, 14, and 28 days of islet implantation. Capsule analysis showed a decrease in cellular adhesion when the islets were encapsulated in the presence of VEGF. Insulin secretion of the islets was higher in the presence of VEGF compared with islets alone at all steps of the study. When 1000 rat islets were transplanted in the presence of VEGF, the glycemia level decreased to 6.2 +/- 0.8 mmol/L after 3 days and remained stable until at least 28 days. In contrast, in the absence of VEGF, the initial decrease in the glucose level was rapidly followed by a relapse in hyperglycemia. In summary, VEGF increased the viability of engrafted encapsulated islets, increasing the duration of a normalized glycemia in diabetic mice following transplantation. Local adjunction of VEGF may therefore improve the clinical outcome of islet transplantation.

Safety in urban areas: the French program "safer city, accident-free districts".

The program, Ville plus sûre, quartiers sans accidents, was launched in 1984, with goals of integrating motorized traffic into urban environments with due regard to local participation and awareness. The initial results show a drop in accidents of approximately 60% a decrease in average speeds, and an especially significant drop in excessively high speeds.

[Angiogenesis and arteriogenesis are increased in the SHR at the pre-hypertensive stage]. / L'angiogenèse et l'artériogenèse sont accrues chez le SHR au stade pré-hypertensif.

OBJECTIVE: A microvascular rarefaction by angiogenic deficiency could promote the onset of hypertension in SHR, in young hypertensive patients and in normotensive descendants of hypertensive parents. We studied the angiogenic potency in prehypertensive SHR, in fibrin chambers implanted in rats, an in vivo model of angiogenesis. METHODS: Four-week pre-hypertensive SHR (n=9) and controls WKY (n=9) were implanted with fibrin gel chambers. The chamber is a cylinder (dia.: 13 mm; H: 5 mm) whose base is perforated with 10 holes of 0.8 mm. The chambers are filled with rat fibrin and implanted (n=4) into the rat dorsal subcutaneous space. After 14 days, vasculo-conjunctive buds have invaded the fibrin gel through the holes and the chambers are removed, fixed and coloured. The intact vascular buds were studied using optical microscopy. The number of vessels counted in central field corresponds to the vascular pedicle, the average number of vessels counted in 3 peripheral fields, represents the vascular branching. The number of arterialised vessels including at least 2 layers of SMC was counted in the central field of each bud. RESULTS: Both rat strains remained normotensive all along the experiment. In SHR fibrin chambers, the number of peripheral vessels (20 +/- 2.6 vs 9.5 +/- 3; p<0.0001) and the number of central arterialized vessels (7.5 +/- 2 vs 2.1 +/- 1.3; p<0.0001) was significantly higher compared to WKY. CONCLUSION: Angiogenesis and arteriogenesis are increased in pre-hypertensive SHR compared to WKY. These results plead against a microvascular rarefaction hypothesis in these genetically hypertensive rats.

[Anti-angiogenic effects of aldosterone antagonists in the fibrin chamber in rats]. / Effets anti-angiogéniques d'antagonistes de l'aldostérone dans la chambre de fibrine chez le rat.

Spironolactone, a diuretic antagonist of aldosterone has an unexplained side effect of amenorrhea which could be due to an angiogenesis inhibition. In this study we compared the effects of spironolactone, canrenone an active metabolite of spironolactone and eplerenone a more selective mineralocorticoid antagonist in rats implanted with a fibrin gel chamber. Perforated plexiglass chambers filled with rat fibrin, spironolactone (50 microM), canrenone (100 microM), eplerenone (500 microM), DMSO (0.05%) and control were implanted into the dorsal subcutaneous space of wistar rats. After 14 days of implantation, an invasion of the fibrin gel chamber by neovascularised buds had occurred through the holes. The number of vessels in the central field and in two or three peripheral fields covering the surface of the bud, were measured for each drug tested and compared to the control. In spironolactone treated chambers, the numbers of peripheral and central vessels were significantly reduced compared to control (p < 0.001). Canrenone, eplerenone and DMSO did not reduce the number of vessels (m +/- ESM, ANOVA followed by Newman-Keuls test). Spironolactone but not canrenone, nor eplerenone inhibited vessels formation in vivo. This antiangiogenic activity appeared to be not related to the antimineralocorticoid effect of spironolactone.

[Large sections in routine breast pathology. A technique adapted to conservative surgery]. / Les coupes larges en pathologie mammaire de routine. Une technique adaptée à la chirurgie conservatrice.

Large block macrosectioning of segmental excision specimens for breast cancer, and especially ductal carcinoma in situ, provides detailed information regarding size of the lesions, extent of spread and margin status which are essential for local recurrence risk assessment. However, the expansion of this technique has been curbed due to its reputation of being technically difficult, time-consuming, costly and providing slides of poor quality. We assessed the feasibility of the large section technique and adapted it to the everyday practice of a routine pathology laboratory. The time spent cutting a large block on a motorized microtome is half the time spent cutting the great number of conventional blocks needed to assess the same amount of tissue. Finally, 4 mm-thick stained large preparations of high quality are produced within 3 days after receiving the specimen. Analysis and report are both more precise and easier since the pathologist is saved the trouble of having to mentally re-assemble a great quantity of numbered small blocks. 805 primary monobloc segmental excision specimens have been examined in this way over the last 50 months period and we advocate its use as a standard procedure for breast-conserving surgery specimen management.

[Activity and cost analysis in surgical pathology. Experience of a French university laboratory using the activity-based costing method]. / Mesure de l'activité et des coûts en ACP hospitalo-universitaire par la méthode ABC (activity-based costing).

Good self-knowledge enables us to have a well- reasoned adaptation to our environment. Starting from this precept based on simple common sense, activity and cost analysis, when applied to medical departments in a university hospital setting, represents a necessary phase in their scientific progression and in the continuation of their university vocation. This is all the more true given the present climate of economic and organizational restructuring of medical facilities. This paper relates the experience of a French surgical pathology department which was assessed for cost effectiveness using the Activity-Based Costing (ABC) method in 1999. This method, which originated in the business world and of which the general concepts are presented here, has given us a keener understanding of the diverse processes involved, their costs and how these costs are arrived at. Moreover, this method has identified the proportion of costs imputable to diagnostic work and of those linked to work specific to a university hospital, in particular teaching and research and development. The results can then be used for a clearer analysis of the figures required by prescribers and health care funding agencies, and, within the department, to enhance perception of work carried out by the entire staff in order to initiate a new type of management centered on activity (Activity-Based Management). Adaptable to any medical department, whatever its organizational structure, independent of the significance of any given code letter and regardless of the rating method used to grade activities, the ABC method also allows for comparisons between structures of a similar nature. The thoughts it inspires on economic performance must take into account the rules of good medical practice, the imperatives of quality assurance, the need for "breathing space" which are indispensable to research and a humanist conception of working relations.

Percutaneous cryotherapy of vascular malformation: initial experience.

The present report describes a case of percutaneous cryotherapy in a 36-year-old woman with a large and painful pectoral venous malformation. Cryoablation was performed in a single session for this 9-cm mass with 24 h hospitalisation. At 2- and 6-month follow-up, the pain had completely disappeared, and magnetic resonance imaging demonstrated a significant decrease in size. Percutaneous cryoablation shows promise as a feasible and apparently safe method for local control in patients with symptomatic venous vascular malformations.