Input of a Multi-Disciplinary Meeting in the Treatment of Osteoarticular Infections in French War Casualties.

INTRODUCTION: Extremity war-wounds present an elevated risk of infection and compromise reconstructive procedures. In a French military hospital, a multi-disciplinary meeting (MDM) was created to standardize the care given to soldiers with osteoarticular infection. The aim of this study was to evaluate the usefulness of MDM decisions. METHODS: An observational case study was performed including the French wounded at war treated for an osteoarticular infection between 2004 and 2016. They were separated into two groups according to their time of management: before (group A) or after (group B) the MDM creation in September 2010. Various operative and bacteriological parameters were analyzed retrospectively. A questionnaire was created to evaluate healthcare professionals' satisfaction toward the usefulness of the MDM on their practice. RESULTS: During the study period, 38 patients were included: 19 in group A and 19 in group B. Initial tests found an infection with one pathogen in 15 patients, an infection with 2 pathogens in 11 patients, and an infection with 3 or more pathogens in 12 patients. Enterobacter cloacae was the most common pathogen. Pseudomonas aeruginosa and Escherichia coli were also frequent. The mean number of samples taken to conduct the bacteriological tests per operating session was significantly higher for group B than for group A. Twelve of the 14 questioned healthcare professionals believed the MDM was very useful in their patient management. CONCLUSION: The MDM seems to have had a beneficial impact on orthopedic surgeon practices. A significant increase of the number of samples taken was the most obvious sign that the French recommended practices for osteoarticular infections were followed since the creation of MDM.

Sequential management of tibial fractures using a temporary unicortical external fixator.

INTRODUCTION: The development of damage control orthopedics (DCO) procedures has led to the development of temporary unicortical external fixators (TUEFs) intended to limit deep infectious complications and facilitate early conversion to internal fixation. METHODS: A retrospective study was conducted in two French military trauma centers, including on patients being treated for tibial fractures with a TUEF (UNYCO® - Orthofix®) followed by an early conversion to intramedullary nailing. RESULTS: Eleven patients with an average age of 41 were included between September 2015 and June 2017. A total of 12 TUEFs were implanted for one closed fracture and 11 open fractures, including one type I, eight types II, and two Gustilo types IIIB. The indication of DCO was related to hemodynamic instability in three cases, to the severity of soft tissue lesions in eight cases, and to the context of treatment in one case. The conversion to IM nailing was made after an average of 7.6 days. No significant loss of reduction was observed until internal osteosynthesis, which was performed with "fixator in place" in ten cases. The coverage of Gustilo type III injuries was performed by free flap transfers at the same time as IM nailing. All the patients were reviewed with an average follow-up of 16.5 months. Bone union was achieved in all cases. Two IM nailing dynamizations were carried out, but no bone grafting was required. Two cases of pandiaphysitis were observed and treated without functional complications. DISCUSSION: Despite a limited number of patients, this study demonstrates the reliability of the TUEF to maintain the reduction of tibial fractures and facilitate early conversion to IM nailing. Unicortical fixation does not prevent septic complications related to the severity of soft tissue injuries.

Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: what is the optimal procedure for the surgical margins? A single center experience.

OBJECTIVES: To compare positive surgical margin rates after robot-assisted and pure laparoscopic radical prostatectomy when neurovascular bundles are preserved, and to identify parameters affecting surgical margin status. METHODS: From March 2004 to January 2009, 279 consecutive prostatectomies with preservation of neurovascular bundles were carried out by the same surgeon: 175 robot-assisted radical prostatectomies and 104 laparoscopic radical prostatectomies. An intraperitoneal Montsouris's technique was used for all cases. Patient's age, body mass index, prostate weight, prostate-specific antigen level, clinical stage, preoperative and postoperative Gleason score, percentage of positive biopsies, pathological stage, and positive surgical margin status were prospectively recorded in an institutional database. The two groups were retrospectively analyzed and compared. RESULTS: Positive surgical margin rates were 17% and 13% for the robot-assisted radical prostatectomy and laparoscopic radical prostatectomy group (P = 0.4), respectively. At multivariable analysis, only prostate-specific antigen level and prostate weight significantly affected the surgical margin status, where the type of procedure (robotic vs laparoscopic) did not have any effect. CONCLUSION: In our single-surgeon experience, prostate-specific antigen levels and prostate weight are predictive of positive surgical margin in patients undergoing nerve-sparing radical prostatectomy, whereas there seems to be no difference between the robot-assisted radical prostatectomy and the laparoscopic radical prostatectomy techniques.

Association between estrogen and androgen receptor genes and prostate cancer risk.

OBJECTIVE: Prostate cancer (PC) is one of the principal causes of death among men. Steroid hormones are involved in normal prostate growth and carcinogenesis. The purpose of our study was to investigate the effects on PC risk of polymorphisms from three steroid hormone receptor genes: the androgen (AR), and the alpha (ESR1) and beta (ESR2) estrogen receptors. DESIGN AND METHODS: The study was performed on a Caucasian population of 1045 PC patients and 814 controls. Using a logistic regression model, the different alleles and genotypes from those polymorphisms were analyzed according to case/control status, the tumor aggressiveness, and the age at onset. RESULTS: A significant association between PC risk and the pooled 4/5, 5/6, and 6/6 genotypes of the GGGA repeat located in the first intron of ESR1 (odds ratio (OR)=3.00, 95% CI=1.32-6.82, P=0.008) was observed. When we stratified the cases, this association was confined to patients with a Gleason score of 2-4 (OR=8.34, 95% CI=2.91-23.91, P<0.0001) or late onset PC (OR=2.91, 95% CI=1.22-6.93, P=0.016). An association between a short AR CAG repeat (less than 17 repeats) was also observed among patients with late onset PC (OR=2.34, 95% CI=1.15-4.76, P=0.019). CONCLUSIONS: These findings suggest that the GGGA repeat from ESR1 and the CAG repeat from AR may be associated with risk of late onset PC.

Effect of genetic variability within 8q24 on aggressiveness patterns at diagnosis and familial status of prostate cancer.

PURPOSE: Recently, two independent loci located at 8q24 that contribute to prostate cancer risk in men of European origin were identified. EXPERIMENTAL DESIGN: Using Bayesian probability network and logistic regression model, we searched for associations between 34 single-nucleotide polymorphisms (SNP) located at 8q24 and the aggressiveness patterns of prostate adenocarcinoma or familial history of cancers in 823 White Caucasian French men. RESULTS: Probability network according to the Markov chain algorithm separated the SNPs into two main groups: The first one was linked to the locus marked by rs6983267 and the second one was linked to the locus marked by rs1447295. When the patients were stratified according to tumor stage and prostate-specific antigen value, the association between the variant genotypes from six SNPs located in the second network and prostate cancer risk was strongest or confined to the patients from the more aggressive classes. However, the association between prostate cancer risk and the CC genotype of rs7841264, which marked the recombination hotspot at 8q24, was confined to patients with the highest Gleason score (odds ratio, 2.15; 95% confidence interval, 1.27-3.64; P=0.004). Interestingly, the G allele of rs6983267 was associated with familial prostate cancer risk. CONCLUSIONS: Our data further support that variability at 8q24 is associated with a high risk of aggressive prostate cancer at diagnosis and is linked with familial history of prostate cancer. These results corroborate that 8q24 SNPs must be evaluated in terms of prostate cancer aggressiveness markers to optimize early diagnosis procedures and management of the disease.

Differential expression of genes related to androgen and estrogen metabolism in hereditary versus sporadic prostate cancer.

The hereditary predisposition to prostate cancer is rare and accounts for <5% of cases. Except for younger age at diagnosis, no phenotypic features have been clearly associated with hereditary prostate cancer. The aim of the study was to analyze the expression of genes related to androgen and estrogen metabolism in both hereditary and sporadic prostate cancers in patients matched for clinicopathologic features. Tissues were obtained from patients included in a national familial prostate cancer registry. From the 120 cases of hereditary forms suggesting autosomal dominant Mendelian inheritance, 21 patients were treated by radical prostatectomy for whom formalin-fixed tissue was available. Twenty-one sporadic cases were then matched according to age, Gleason score, and pathologic stage. Immunohistochemistry was done on tissue microarray using antibodies directed against androgen receptor (AR), estrogen receptor alpha (ERA), estrogen receptor beta, 5alpha-reductase I and II, aromatase, and the proliferation marker Ki67. The percentage of AR-positive cancer cells was higher in hereditary cancer compared with sporadic cases (P < 0.004). In contrast, the mean number of ERA-positive stromal cells was lower in hereditary versus sporadic cancer (P < 0.03). This differential expression of AR and ERA suggests that a specific pattern of hormone receptors is associated with hereditary predisposition to prostate cancer.

PGE2 and LTB4 tissue levels in benign and cancerous prostates.

PGE2 and LTB4 are involved in inflammation and carcinogenesis in several tissues but have not been studied in prostate cancer and hyperplasia until now. We therefore measured PGE2 and LTB4 productions in a total of 206 prostate tissues from 116 patients including benign hyperplastic (90), pericancerous (106) and cancerous samples (10). We also analysed the influence of inflammation levels, prostate volume and glandular to epithelial ratio. PGE2 and LTB4 concentrations were measured using specific enzyme immunoassay kits. There was a correlation between PGE2 level, prostatic volume, inflammation score, and decreased glandular surface. By contrast, there was no correlation between LTB4 levels and inflammation or PGE2 production. Cancerous samples had higher LTB4 levels than pericancerous samples, but there was no difference in PGE2 levels. PGE2 and inflammation may be associated to stromal benign prostatic hyperplasia whereas LTB4 may play a role in prostate carcinogenesis.

[How is prostate cancer screening perceived by men 50 to 70 years of age? Analysis based on 1,774 screened individuals]. / Comment le dépistage du cancer de la prostate est-il perçu par les hommes de 50 a 70 ans Analyse a partir de 1774 individus dépistés.

INTRODUCTION: The rationale for mass screening for prostate cancer remains controversial. Apart from the scientific debate, we wanted to evaluate the opinion of prostate cancer screening candidates concerning the practical modalities of this screening and assess the impact of various personal, medical or social factors on their replies. MATERIAL AND METHOD: Following a screening campaign in a French district, 1,774 men, 50 to 70 years of age, who completed screening were interviewed by questionnaire concerning the duration, frequency, mode of blood sampling and the cost of screening. Medical history, family history and lifestyle were also evaluated. RESULTS: Among 1,774 candidates who returned an interpretable questionnaire during the screening campaign (participation rate: 31%), 27.1% of subjects interviewed declared that the personal financial cost would be an obstacle to screening, 5.1% considered that collection of a blood sample from the cubital fossa would be an obstacle to screening, 6.5% considered that one PSA per year was too frequent, and 8.1% considered that screening between the ages of 50 and 70 years was too long. CONCLUSION: More than 90% of men who participated in a prostate cancer screening campaign appear to be in favour of continuation of screening according to the current modalities provided it is free of charge. The acceptance rate was better for men with a family history of prostate cancer, men who had already had a PSA assay, men living alone and men under 60 years of age.

Combination of polymorphisms from genes related to estrogen metabolism and risk of prostate cancers: the hidden face of estrogens.

PURPOSE: The association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated. PATIENTS AND METHODS: The study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers. RESULTS: The VV (high activity) genotype of the V432L polymorphism from CYP1B1 (odds ratio [OR] = 1.36; 95% CI, 1.03 to 1.79; P = .031), and the long allele (> 175 bp) of the TTTA repeat from CYP19 (OR, 1.26; 95% CI, 1.08 to 1.47; P = .003) were significantly associated with the risk of prostate cancer. An additive effect was observed when we combined the two at-risk alleles (OR = 1.63; 95% CI, 1.24 to 2.13; P < .001). The association was stronger for the CYP1B1 VV genotype (OR = 1.55; 95% CI, 1.13 to 2.13; P = .007) among the group of patients with highly aggressive disease. Stratification by age at onset showed that the associations of CYP1B1 and CYP19 variants were largely confined to the younger prostate cancer patients. CONCLUSION: This association between polymorphisms from genes related to estrogen metabolism and prostate cancer risk suggest new clinical considerations in the management of prostate cancer: the development of new prevention trials based on genetic profiling and the evaluation of specific inhibitors involving the estrogen pathways.

[Impact of obesity on PSA in prostate cancer screening]. / Impact de l'obésité sur le PSA lors du dépistage du cancer de la prostate.

OBJECTIVE: Obesity is associated with changes of serum levels of androgens and oestrogens which could modulate prostate metabolism. The objective of this study was to investigate a possible correlation between the PSA level and the degree of obesity in a candidate population for prostate cancer screening in order to determine whether the PSA level needs to be adapted before performing biopsy. MATERIAL: During a screening campaign in a French district, serum PSA results and body mass index (BMI) were available for 541 men. These men were divided into 4 groups of corpulence: Normal (BMI < 25), Overweight (25 < or = BMI < 30), Stage I obesity (30 < or = BMI < 35), Stage II + III obesity (BMI > or = 35). The PSA levels of these various groups were compared, and a correlation between BMI and PSA was investigated. RESULTS: The mean PSA in each group was inversely proportional to BMI, with mean PSA levels of 3.7, 2.9, 2.6 and 1.5 for Normal, Overweight, Obesity I and Obesity II + III groups, respectively. A significant difference was observed between these groups (p = 0.03) and an inverse correlation was also observed between BMI and PSA (r = 0.1, p = 0.01). CONCLUSION: In a population submitted to prostate cancer screening, PSA is lower as BMI increases. An adaptation of the PSA screening cutoff value according to BMI should be investigated.

BRCA2 mutation screening is clinically relevant in breast and early prostate cancer families.

It is known that in some families an association exists between breast and prostate cancer. Several reports have suggested that BRCA2 mutations may be associated with an increased risk of these cancers. Herein, we report three cases of early onset of prostate cancer in families with female and male breast cancers. In each case, the familial phenotype is associated with a mutation of the BRCA2 gene. More generally, genetic counseling, including screening for BRCA2 mutations, should become standard practice in kindred with prostate and breast cancers.

Low-activity V89L variant in SRD5A2 is associated with aggressive prostate cancer risk: an explanation for the adverse effects observed in chemoprevention trials using 5-alpha-reductase inhibitors.

OBJECTIVE: The 5-alpha-reductase type 2 (5A2) enzyme catalyses the irreversible conversion of testosterone to dihydrotestosterone, the most active androgen in the prostate. This key enzyme in prostate gland physiopathology has recently been targeted by using inhibitors for chemoprevention of prostate cancer. However, some controversies have arisen by the observation of greater than expected high-grade tumours in men diagnosed with prostate cancer in the finasteride chemoprevention trial. To help understand the impact of prolonged exposure to low 5A2 activity on prostate cancer risk, we analysed the rather common genetic V89L polymorphism, which has previously been well characterised functionally for determining low enzymatic activities. METHODS: The study was performed on 1605 white Caucasian French men categorised in 803 patients with prostate adenocarcinoma and 802 matched healthy male controls. The different alleles and genotypes were analysed according to case-control status and the aggressiveness pattern of the tumours. RESULTS: The V89L amino acid substitution leading to the homozygous genotype LL increased the risk of clinically significant disease (odds ratio [OR]=1.89, 95% confidence interval (%95 CI), 1.07-2.74; p=0.0017) and was also associated with the most aggressive patterns of the disease (OR=2.56, 95%CI, 1.41-4.63; p=0.002). CONCLUSIONS: Our data confirm in a large and homogeneous Caucasian French population that the low-activity V89L variant is associated with an increased risk of aggressive prostate cancer. These results corroborate that long-term exposure to 5A2 inhibitors (chemoprevention) must be evaluated in terms of risk of prostate cancer adverse effects.

Relevance of the prostate-specific antigen (PSA) nanotest compared to the classical PSA test in the organized mass screening of prostate cancer.

OBJECTIVE: To assess the reliability of a new measurement of prostate-specific antigen (PSA) using a blotting-paper assay (nanotest) compared to the standard PSA immunoassay. SUBJECTS AND METHODS: The PSA level was measured in 205 men volunteers (median age 70 years, range 41-75) using a nanotest and a standard PSA immunoassay, collected at the same time; 30 microL of capillary blood placed on to a blotting paper were collected for the nanotest and sent by mail to the same laboratory for the two assays. The results were compared statistically using the Spearman test, the intraclass correlation coefficient and the Bland-Altman test. RESULTS: The nanotest threshold for an abnormal PSA level was 78 pg/mL, which corresponded to a standard PSA value of 3 ng/mL, with a sensitivity of 100%. There was a significant correlation (r = 0.98, Spearman test; P < 0.001) between the nanotest and the standard PSA assay. The intraclass correlation coefficient was 0.87. The Bland-Altman test showed a good agreement between the nanotest and the standard PSA assay, but there was an increasing proportional difference with increasing PSA value. CONCLUSION: There was a very high correlation between the nanotest and the standard PSA assay, especially for standard PSA levels of <5 ng/mL. Economic and clinical studies are indicated to confirm the utility of the nanotest in organized mass screening of prostate cancer.

[Cystomanometric study of bladder sensation during sacral neuromodulation test]. / Etude cystomanométrique de la sensation vésicale pendant le test de neuromodulation sacrée.

PURPOSE: Prospective clinical and urodynamic study evaluating modification of bladder sensation during sacral neuromodulation (SNM). MATERIALS AND METHODS: 24 consecutive patients with non-neurological hyperactive bladder underwent an SNM test. Questioned about their symptoms before and during the test by the urinary handicap assessment scale, patients were divided into two groups: A (improved) and B (not improved). Group A consisted of patients obtaining 50% improvement of their symptoms with SNM followed by return of symptoms at the end of the test, while the other patients constituted group B. We then compared the cystomanometric results according to their clinical response. RESULTS: The mean age was 53 years: 10 patients with a good response constituted group A (n=10, i.e. 42%) and 14 patients with a poor response constituted group B (n=14, i.e. 58%). Clinically, in patients with a good response, SNM decreased urge incontinence by 100%, day-time frequency by 89% and protections by 55%. Urodynamic assessment in group A during the test demonstrated a significant increase of +23% of bladder capacity (p<0.01), +57% of the volume of onset of the first unstable contraction (p<0.004), +83% of bladder volume to the first urge to urinate BI (p<0.001) and +46% to urgency B3 (p<0.04). During SNM, cystometry revealed that 1 or 2 bladder filling volumes were increased at B1 and/or B3 in 100% of improved subjects. In contrast, 1 or 2 volumes decreased at B1 and/or B3 in 58% of non-improved subjects. No significant difference of intensity of unstable contractions was observed between the 2 groups during SNM (p=0.31). CONCLUSION: A significant correlation was observed between the two methods of clinical and urodynamic assessment. Our results suggest the use of the cystomanometric increase of bladder volume at B1 and B3 as selection criterion for candidates for SNM with non-neurological hyperactive bladder.

Differential expression of 37 selected genes in hormone-refractory prostate cancer using quantitative taqman real-time RT-PCR.

Progression of prostate cancer to androgen independence remains the primary obstacle to improved survival. The development of more effective treatments depends on our understanding of the molecular events associated with the hormone-refractory stage. We quantified, among 90 screened genes, the expression of 37 target genes, using real-time quantitative RT-PCR. Gene expression was studied in 13 samples of HPRC compared to 33 clinically localised cancers and normal prostate tissue. We identify 19 genes with significant differential expression in HRPC compared to localised prostate cancer. Genes with decreased expression included receptors for growth factors, MMR genes and the serine protease hepsin. Analysis of increased gene expression confirmed the importance of AR upregulation and highlighted genes not previously linked to HRPC, including enzymes involved in steroid synthesis and the antiapoptotic factor survivin. Progression of prostate cancer to the hormone-refractory state is associated with differential gene expression, which may prove useful for both understanding disease progression and the development of new therapeutic approaches.

Molecular profiling of benign prostatic hyperplasia using a large scale real-time reverse transcriptase-polymerase chain reaction approach.

PURPOSE: Benign prostatic hyperplasia (BPH) is characterized by a hyperplastic growth of epithelial and stromal cells in the prostate. Despite the high prevalence of the disease little is known regarding the molecular etiology of BPH. Therefore, a comparison of gene expression patterns between normal prostate, BPH and prostate cancer could provide insights into the pathogenic mechanisms of the disease and identify candidate genes that could be targeted for therapeutic use. MATERIALS AND METHODS: Prostate tissue specimen were obtained from 30 patients undergoing adenomectomy for BPH. Adenoma weight was less than 60 gm in 15 patients and more than 60 gm in the remainder. Normal prostate tissue was obtained from 15 patients undergoing radical prostatectomy for cancer from areas selected for absent tumor and BPH. Two pools of organ confined prostate cancer were also analyzed. We quantified in the 5 pools of tissues the expression of 327 genes using real-time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: A total of 23 genes showed increased expression in BPH with a fold change of at least 2.5 between normal prostate and the 2 BPH groups, of which most were normal or down-regulated in prostate cancer. Seven genes showed decreased expression in BPH with a fold change of at least 3.5 between normal prostate and BPH. Most of them were also normal or down-regulated in prostate cancer. CONCLUSIONS: We identified a set of genes up-regulated in BPH compared to normal prostate tissue and often prostate cancer, including genes previously implicated in BPH and others not previously linked to this disease to our knowledge. Further investigations are now warranted to determine the clinical relevance and therapeutic potential of these genes.

Expression in bladder transitional cell carcinoma by real-time quantitative reverse transcription polymerase chain reaction array of 65 genes at the tumor suppressor locus 9q34.1-2: identification of 5 candidates tumor suppressor genes.

Frequent deletions on 9q34.1-2 were reported in bladder transitional cell carcinoma. High deletion mapping studies delimited a critical interval between markers D9S61 and D9S66, which is highly susceptible to contain a tumor suppressor gene. Expression level of the 65 genes localized in this region was analyzed by real-time quantitative RT-PCR, comparing tumor to normal urothelium. Five genes exhibited a significantly reduced expression level: C9orf9, KIAA0625, ABL1, LAMC3 and KIAA1857-netrin-G2, which exhibited the most significant downregulation (p=0.0007). KIAA1857-netrin-G2 belongs to the netrins and might then be a tumor suppressor gene in bladder cancer, as netrin1 receptor DCC has been implicated in tumorigenesis.

Adherence to an annual PSA screening program over 3 years for brothers and sons of men with prostate cancer.

OBJECTIVE: To assess the adherence to an annual PSA screening program conducted over 3 years in first-degree relatives of a sample of men with prostate cancer, and to identify characteristics of men who failed to undergo the full screening process. PATIENTS AND METHODS: Out of 747 candidates that were eligible for the screening program (asymptomatic brothers and sons aged between 40 and 70 years of men diagnosed with prostate cancer) 640 were contacted. The screening program entailed annual serum PSA testing over a 3-year period, during which every candidates attendance was recorded. At the outset, each candidate was requested to complete a questionnaire regarding their socio-professional characteristics, their level of anxiety and their attitude towards genetic susceptibility. RESULTS: 442 (69%) candidates agreed to enter the study and 420 filled out the questionnaire. During the 3-year period, 50 candidates (12%) who had accepted the first year screening refused to undergo subsequent PSA tests. These men were younger ( p=0.015), more anxious (p=0.037 ) and to have more than one affected first-degree relative ( p=0.028 ). CONCLUSIONS: The crucial and challenging step in the adherence to a screening program was the initial recruitment. Once recruited, adherence rate after 3 years was very high (88%). Identifying factors that help predict men who might leave the screening process may provide us means of improving their compliance in the future.

Laparoscopic robotic-assisted ileal conduit urinary diversion in a quadriplegic woman.

Urinary diversion is a therapeutic option in quadriplegic patients with poor lower urinary tract conditions, but it is an invasive procedure. Laparoscopic techniques are less invasive, but are technically demanding, and only a few surgical teams are able to complete such a complex procedure endoscopically. Robotics bring an unprecedented control of surgical instruments, shorten the learning curve, and allow open surgeons to apply more easily their technical skill to the laparoscopic approach. This complex case of laparoscopic ileal conduit in a quadriplegic woman was completed by our team with the Da Vinci system after 6 months of clinical experience in robotic surgery.