[Cyberattack at Dax hospital: Presentation of the facts, consequences and feedback]. / Cyberattaque à l'hôpital de Dax : exposition des faits, conséquences et retour d'expérience.

Cybersecurity is a major issue in today's world. Health structures are not immune to attacks aimed at stealing valuable sensitive data, demanding a ransom, disrupting or paralyzing a system for political purposes. The Dax Hospital Center (France) had to deal with such an attack in February 2021, bringing the entire computer system to its knees. Radiotherapy, a highly technological specialty and dependent on computers, is a very sensitive sector: unlike other specialties, computer malfunctions prevent any treatment of patients. Faced with this threat which is a reality and of which we bring here a testimony based on our experience, it is important to reflect on the human and technological means in cooperation with the IT specialists to reduce this risk as much as possible but also to be able in the event of an attack to reconstruct the system as quickly as possible and ensure continuity of care.

Oncological and functional results of robotic salvage radical prostatectomy after permanent brachytherapy implants.

PURPOSE: To evaluate the feasibility of robotic salvage prostatectomy for local recurrence after permanent brachytherapy implants for prostate cancer. PATIENTS AND METHODS: Seven patients were operated by robotic salvage prostatectomy with or without pelvic lymph node dissection between October 2007 and March 2012, for a local recurrence after iodine 125 permanent brachytherapy implants. Local recurrence was proved by prostate biopsies, once biochemical relapse was diagnosed and imaging assessment performed. RESULTS: The average age of a patient at the time of diagnosis was 66 years (62-71 years). The median nadir prostate specific antigen (PSA) serum concentration after brachytherapy was 1.29ng/mL (0.6-2.1ng/mL), obtained after a median of 12 months (7-21 months). The average [PSA] before robotic salvage prostatectomy was 6.60ng/mL (4.17-13.80ng/mL). [PSA] at 1 and 3 months after prostatectomy was less than 0.05ng/mL in five patients. [PSA] remained below 0.05ng/mL for six patients at 12 and 24 months. One month after robotic salvage prostatectomy, all patients had at least partial urinary incontinence. At 12 and 24 months after robotic salvage prostatectomy four patients have regained full urinary continence. In terms of erectile function at 24 months, three patients retained erectile function with possible sexual intercourse. CONCLUSION: Robotic salvage prostatectomy appears to be a reliable treatment in terms of oncological outcome with convincing results both for urinary continence and erectile function for selected patients with local recurrence after permanent brachytherapy implants.

[Adjuvant radiotherapy for bladder cancer in patients with risk of locoregional recurrence: Who, what and how?] / Radiothérapie adjuvante des tumeurs de vessie à risque de rechute locorégionale : pour qui, pourquoi et comment ?

Radical cystectomy with extended pelvic lymph node dissection remains the standard of care for non-metastatic muscle-invasive bladder cancer. Locoregional control is a key factor in the outcome of patients since it is related to overall survival, metastasis-free survival and specific survival. Locoregional recurrence rate is directly correlated to pathological results and the quality of lymphadenectomy. In addition, while pre- or postoperative chemotherapy improved overall survival, it showed no impact on locoregional recurrence-free survival. Several recent publications have led to the development of a nomogram that predicts the risk of locoregional recurrence, in order to identify patients for which adjuvant radiotherapy could be beneficial. International cooperative groups have then come together to provide the rational for adjuvant radiotherapy, reinforced by recent technical developments limiting toxicity, and to develop prospective studies to reduce the risk of relapse. The aim of this critical literature review is to provide an overview of the elements in favor of adjuvant radiation for patients treated for muscle-invasive bladder cancer.

Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.

OBJECTIVES: Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity. METHODS: We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)). RESULTS: Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease. CONCLUSIONS: The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.

[Guidelines for delineation of pelvic lymph nodes in anal cancer treatment]. / Recommandations pour la délinéation des aires ganglionnaires pelviennes dans le cancer du canal anal.

Squamous cell anal cancer is a rare malignancy, its incidence increases due to higher exposure of the young adults to risk factors. The current management is based on chemoradiotherapy, which is highly effective and achieves locoregional control but causes important morbidity. Improvement of radiation technique such as intensity modulated radiation therapy has led to reduce acute toxicities, but also requires an accurate delineation of the target volumes in order not to underestimate potential and pathological sites resulting in an increase of the locoregional failures. PET scanner has an important place in the pretreatment work-up for staging and targeting the delineation of the volumes, allowing to select patients with localized disease, avoid geographic miss and appropriately boost nodal disease. The study of recurrences sites has not yet provided a real mapping of the recurrences depending on the treatment volumes. Different radiation oncologist cooperative groups have published guidelines and tools for delineation, in order to provide homogeneity but also customize the management of anal carcinoma.

VEGF, VEGFR-1, VEGFR-2, microvessel density and endothelial cell proliferation in tumours of the ovary.

VEGF is an angiogenic factor with potent endothelial cell (EC) proliferative actions. Our aim was to investigate whether expression of VEGF and its receptors and EC proliferation differ between ovarian tumour types and regions of the vasculature. VEGF, VEGFR-1, VEGFR-2 and EC proliferation were examined immuno-histochemically, and in situ hybridisation (ISH) studies of VEGF mRNA expression were performed and assessed in regions of high (HVD) and average (AVD) vessel density. VEGF immunostaining was significantly stronger in HVD regions of malignant compared with borderline serous tumours. VEGF immunostaining did not differ between tumour types; however, the percentage of VEGFR-1- and VEGFR-2-positive vessels was significantly lower in mucinous tumours. No differences were observed between HVD and AVD regions. VEGF ISH signal was observed in 2/7 borderline mucinous tumours, 8/14 malignant serous tumours and 5/13 benign tumours. The EC proliferation index was significantly lower in the HVD regions of serous relative to benign tumours. A negative correlation between VEGFR-1 immunostaining and microvessel density was observed in benign and serous tumours. However, EC proliferation index and VEGFR-1 positivity were positively correlated in benign tumours. Our results suggest that VEGF may play a role in the control of angiogenesis in serous and benign tumours but it does not appear to contribute to the previously reported higher microvessel density in mucinous tumours or to influence heterogeneity of microvessel density in ovarian tumours.

Macrophages and microvessel density in tumors of the ovary.

Macrophages are members of the mononuclear phagocyte system and synthesize and release many angiogenesis stimulators and inhibitors. Previous studies have demonstrated heterogeneous macrophage populations in ovarian tumors. The aim of this study was to compare macrophage number between different types of ovarian tumors and between regions of high (HVD) and average (AVD) microvessel density (MVD). Macrophages were visualized using CD68 antibody. Previously determined regions of HVD and AVD were located on CD68 immunostained sections and image analysis software was used to count the number of positively stained cells per square millimeter. CD68-positive macrophage number did not differ between benign, mucinous, and serous ovarian tumors or between regions of HVD and AVD (ANOVA; P > 0.05). In both HVD and AVD regions of benign tumors, macrophage number positively correlated with MVD (Spearman rank correlation coefficient; P < 0.03). In contrast, a small but significant negative correlation between macrophage number and MVD was observed in HVD regions of serous tumors (Spearman rank correlation coefficient; P > 0.05). Macrophage infiltration does not appear to differ between ovarian tumor types; however, macrophages may have a positive influence on the vascularization of benign ovarian tumors.

Microvessel density and vascular basement membrane immunostaining in tumours of the breast.

There is a well established correlation between increased breast tumour microvessel density (MVD) and reduced prognosis. The aims of this study were to investigate (1) if MVD is elevated in regions other than 'hotspots' of node positive versus node negative breast tumours, and (2) to quantitate the percentage of vessels without vascular basement membrane (VBM) components in high vascular density (HVD) and average vascular density (AVD) regions of node positive and node negative breast tumours. Serial sections were immunostained for CD31 and double-stained for CD31 and collagen IV (CollIV), laminin (LAM) or heparan sulphate proteoglycan (HSPG). Microvessel counts were obtained from HVD and AVD regions and the number of VBM positive vessels were expressed as a percentage of total CD31 positive vessels. MVD was significantly higher in both the HVD and AVD regions of node positive compared with node negative breast tumours (t-test; P < 0.03). The average percent vessels positive for CollIV, LAM or HSPG ranged from 18%-45% and did not differ between node positive and negative breast tumours (t-test; P > 0.05). No differences were observed in VBM immunostaining between regions of HVD and AVD (t-test; P > 0.05). These results demonstrate that vascular density is elevated throughout node positive breast tumours, rather than just in 'hotspots', and show that there is no apparent difference in the percentage of VBM-naked vessels in node positive versus node negative breast tumours.

Increased microvessel density in mucinous compared with malignant serous and benign tumours of the ovary.

Microvessel density of benign, borderline and malignant ovarian tumours was studied immunohistochemically using antibodies to the endothelial cell markers CD31, CD34 and factor VIII-related antigen. Microvessel density was compared in tumours of different histological subtype, stage and patient outcome. CD31-immunostained sections were examined and regions of high and average microvessel density were selected. Identical regions were located on CD34- and factor VIII-related antigen-immunostained serial sections and microvessel counts obtained and converted to vessels mm(-2). CD31 and CD34 immunostaining revealed increased microvessel density in both the high and average vessel density regions of mucinous (222.4 +/- 24.8; 79.9 +/- 8.5) compared with serous (105.4 +/- 20.7; 33.3 +/- 6.8) and benign (84.4 +/- 19.4; 20.4 +/- 4.4) tumours (P < 0.001). CD31 and CD34 immunostaining also revealed increased microvessel density in early-stage mucinous tumours (234.6 +/- 28.2; 87.8 +/- 9.2) compared with that observed in both early- (72.8 +/- 15; 12.9 +/- 2.4) and late- (115.6 +/- 26.5; 29.8 +/- 8.5) stage serous tumours (P < 0.001). No differences in microvessel density in samples from patients with differing outcomes were observed (P > 0.05). Reduced factor VIII-related antigen compared with CD31 and CD34 immunostaining was observed in both borderline and malignant mucinous and serous tumours (P < 0.02) but not in benign tumours (P > 0.05). Our results contradict the putative association between increased microvessel density and poor prognosis and suggest that the level and control of angiogenesis may differ between ovarian tumour types.

Reduced vascular basement-membrane immunostaining in mucinous tumours of the ovary.

Tumour vasculature is heterogeneous, exhibiting a range of vessel densities and the vascular basement membrane (VBM) of tumour blood vessels may be fragmented or absent. Increased microvessel density (MVD) has been reported in mucinous ovarian tumours as compared with other histologic sub-types. We hypothesized that VBM immunostaining differs between regions of the ovarian tumour vasculature and between ovarian tumour types exhibiting different MVD. Serial sections from 56 ovarian tumours were immunostained using antibodies to the VBM components collagen IV, heparan sulphate proteoglycan and laminin, and the endothelial cell marker CD31. Regions of high and average MVD were selected, and the number of vessels positive for each VBM component were counted and expressed as a percentage of the number of CD31-positive vessels. The percentage of VBM-positive vessels did not differ between the high and average MVD regions of borderline or malignant, mucinous and serous tumours. The percentage of VBM-positive vessels in mucinous tumours was less than that observed in malignant and borderline serous tumours and benign tumours (p < 0.02). Possible explanations for these findings are (i) that VBM turnover is similar throughout the vasculature; (ii) that the VBM is present both during angiogenesis and in the newly formed vessels of high MVD regions; or (iii) that an alternative angiogenesis mechanism is utilized in different ovarian tumour types, or even between different regions of the same tumour.

The effects of P2 purinoceptor agonists on the isolated portal vein of the guinea pig.

UTP, ATP and several of its analogues enhanced contractions of the longitudinal smooth muscle layer of the guinea-pig portal vein. The rank order of potency was 2-methylthioATP > alpha, beta-methyleneATP > adenosine tetraphosphate > or = beta, gamma-methyleneATP > or = ATP = UTP > > adenosine. Suramin (100 microM) blocked the contractile effects of 2-methylthioATP and alpha,beta-methyleneATP, but not those of ATP and adenosine tetraphosphate. The P1 purinoceptor antagonist, 8-phenyltheophylline (10 microM), was without effect on the response to ATP. Field stimulation (5 s trains every 100 s, 1 ms, 55 V) caused frequency-dependent contractions that were partially reduced by the noradrenergic neurone blocking drug; BW 172C58 (4-benzoyl-xylocholine, 10 microM), but not by suramin. alpha,beta-MethyleneATP was more potent than beta,gamma-methyleneATP, UTP and adenosine tetraphosphate in partially inhibiting field stimulation-induced contractions of the portal vein; its effects, but not those of adenosine tetraphosphate, were reduced by suramin. These results indicate that the guinea-pig portal vein contains P2 purinoceptors; these include a P2x subtype, mediating contraction.