Congenital Leishmaniasis in a Newborn Infant Whose Mother was Coinfected With Leishmaniasis and HIV.

In utero transmission of Leishmania infantum is the putative mechanism of congenital leishmaniasis. However, this hypothesis is based on limited research. In addition, the consequences for infant newborn development remain to be clarified by additional data. We report here the occurrence, specific management, and monitoring of congenital leishmaniasis in a newborn infant whose mother was coinfected with leishmaniasis and human immunodeficiency virus; transplacental transmission, confirmed by overt clinical disease at birth, was documented, which provides, to our knowledge, the first evidence of hepatic and neurologic impairment in an infant with congenital visceral leishmaniasis.

Astaxanthin Complexes to Attenuate Muscle Damage after In Vivo Femoral Ischemia-Reperfusion.

(1) Background: Reperfusion injury refers to the cell and tissue damage induced, when blood flow is restored after an ischemic period. While reperfusion reestablishes oxygen supply, it generates a high concentration of radicals, resulting in tissue dysfunction and damage. Here, we aimed to challenge and achieve the potential of a delivery system based on astaxanthin, a natural antioxidant, in attenuating the muscle damage in an animal model of femoral hind-limb ischemia and reperfusion. (2) Methods: The antioxidant capacity and non-toxicity of astaxanthin was validated before and after loading into a polysaccharide scaffold. The capacity of astaxanthin to compensate stress damages was also studied after ischemia induced by femoral artery clamping and followed by varied periods of reperfusion. (3) Results: Histological evaluation showed a positive labeling for CD68 and CD163 macrophage markers, indicating a remodeling process. In addition, higher levels of Nrf2 and NQO1 expression in the sham group compared to the antioxidant group could reflect a reduction of the oxidative damage after 15 days of reperfusion. Furthermore, non-significant differences were observed in non-heme iron deposition in both groups, reflecting a cell population susceptible to free radical damage. (4) Conclusions: Our results suggest that the in situ release of an antioxidant molecule could be effective in improving the antioxidant defenses of ischemia/reperfusion (I/R)-damaged muscles.

Ductal adenocarcinoma of the prostate: Clinical and biological profiles.

BACKGROUND: Ductal adenocarcinoma (DAC) is a rare and aggressive subtype of prostate cancer (PCa). In the present study, we analyzed the clinical and biological characteristics of DAC, in comparison with high grade conventional acinar PCa. METHODS: Samples and data were retrospectively collected from seven institutions and centrally reviewed. Immunohistochemistry was performed on tissue microarrays to assess the expression of candidate proteins, based on the molecular classification of PCa, including ERG, PTEN, and SPINK1. SPOP mutations were investigated from tumor DNA by Sanger sequencing. Relationships with outcome were analyzed using log-rank analysis and multivariable Cox regression. RESULTS: Among 56 reviewed prostatectomy specimens, 45 cases of DAC were finally confirmed. The pathological stage was pT3 in more than 66% of cases. ERG was expressed in 42% of DAC, SPINK1 in 9% (all ERG-negative), and two cases (ERG-negative) harbored a SPOP mutation. Compared to high grade conventional PCa matched for the pathological stage, cell proliferation was higher (P = 0.04) in DAC, and complete PTEN loss more frequent (P = 0.023). In multivariate analysis, SPINK1 overexpression (P = 0.017) and loss of PSA immunostaining (P = 0.02) were significantly associated with biochemical recurrence. CONCLUSION: these results suggest that, despite biological differences that highlighted DAC aggressiveness, the molecular classification recently proposed in conventional PCa could also be applied in DAC.

Xanthomatous Posttraumatic Fibro-Osseous Lesion of the Rib: A Rare and Underrecognized Entity. Case Report and Literature Review.

Posttraumatic fibro-osseous lesion (PTFOL) is a rare lesion that typically affects the ribs and is probably a posttraumatic reactive process. Because PTFOL is often misdiagnosed as fibrous dysplasia, osteoid osteoma, benign fibrous histiocytoma or rib metastases, chest wall resection, leading to a significant morbidity, is the main treatment modality. We report the case of a 30-year-old male patient with no history of previous trauma presenting with chest pain. Computed tomography scan showed an eighth left rib well-defined ovoid and hypodense lesion with circumferential sclerotic margin and no cortical breakthrough. Posterolateral thoracotomy was performed and a histological diagnosis of xanthomatous posttraumatic fibro-osseous lesion of the rib was made. PTFOL is a benign lesion that should be recognized to avoid unnecessary surgical treatment and complications. We provide a summary of clinical, histopathological, and radiological aspects of PTFOL and discuss differential diagnoses.

Balanced Translocations Disrupting SMARCB1 Are Hallmark Recurrent Genetic Alterations in Renal Medullary Carcinomas.

BACKGROUND: Renal medullary carcinoma (RMC) is a rare and highly aggressive neoplasm that most often occurs in the setting of sickle cell trait or sickle cell disease (SCD). Most patients present with metastatic disease resistant to conventional chemotherapy, and therefore there is an urgent need for molecular insight to propose new therapies. OBJECTIVE: To determine the molecular alterations and oncogenic pathways that drive RMC development. DESIGN, SETTING, AND PARTICIPANTS: A series of five frozen samples of patients with RMC was investigated by means of gene expression profiling, array comparative genomic hybridization, and RNA and whole exome sequencing (WES). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA and DNA sequencing read data were analyzed to detect gene fusions and somatic mutations. Gene fusions mutations were validated by real-time polymerase chain reaction and fluorescence in situ hybridization. Gene expression profiling was analyzed by unsupervised hierarchical clustering and Gene Set Enrichment Analysis (Broad Institute, Cambridge, MA, USA). RESULTS AND LIMITATIONS: We observed inactivation of the tumor suppressor gene SMARCB1 in all tumors. In all four cases developed in patients with SCD, we identified an original mechanism of interchromosomal balanced translocations that disrupt the SMARCB1 sequence and thus contribute to its inactivation. Gene expression profiling revealed that RMC shares common oncogenic pathways with pediatric malignant rhabdoid tumors, another tumor subtype characterized by SMARCB1 deficiency. CONCLUSIONS: RMCs are characterized by an original mechanism of interchromosomal balanced translocations that disrupt the SMARCB1 sequence. WES reveals that RMCs show no other recurrent genetic alteration and an overall stable genome, underscoring the oncogenic potency of SMARCB1 inactivation. PATIENT SUMMARY: Our comprehensive molecular study supports a pivotal role of the tumor suppressor gene SMARCB1 in the development of renal medullary carcinoma. The use of therapeutic strategies based on the biologic effects of its inactivation should now open new perspectives for this typically lethal malignancy.

A case report of reninoma: radiological and pathological features of the tumour and characterization of tumour-derived juxtaglomerular cells in culture.

CASE REPORT: A 20-year-old woman presented with malignant hypertension associated with hypokalemia, metabolic alkalosis and elevated plasma renin and aldosterone levels. Computed tomography angiography (CTA) evidenced a 22 mm tissular mass in the posterior cortex of the left kidney, and 18F-flurodeoxyglucose PET (18-FDG PET) imaging showed no hypermetabolism of the tumour. Following nephron-sparing surgery, blood pressure and potassium levels rapidly normalized, allowing interruption of all treatments within 2 weeks. DISCUSSION: Reninoma is a rare juxtaglomerular cell tumour (JGCT) producing excessive amounts of renin resulting in severe hypertension. Pathological studies revealed that tumoural cells highly expressed renin and contained electron-dense structures, typical of renin-containing granules. Tumoural cells also exhibited the vascular cell surface marker CD34, but, in contrast with previous reports, did not express the tyrosine-protein kinase Kit (cKit or CD117). Dissociation of the tumour allowed to obtain confluent cultures of elongated smooth muscle actin (SMA)-positive cells producing high amounts of renin. However, after the first passage, subcultured human juxtaglomerular cells rapidly lost renin and CD34 expressions and their ability to produce renin. CONCLUSION: The present case of reninoma emphasizes the need for CTA in the etiologic work up of otherwise unexplained severe hypertension. 18-FDG PET imaging showed no hypermetabolism of the tumour, in accordance with its reported benignity. Pathological studies further emphasized that high expressions of renin and CD34 are typical hallmarks of reninoma. Although CD117 has been proposed to represent a reliable marker of JGCT, the present findings indicate that reninomas may not always express this marker.

Extra- and intracranial cerebral vasculitis in giant cell arteritis: an observational study.

Recognizing giant cell arteritis (GCA) in patients with stroke may be challenging. We aimed to highlight the clinical spectrum and long-term follow-up of GCA-specific cerebrovascular accidents. Medical charts of all patients followed in a French Department of Internal Medicine for GCA between January 2008 and January 2014 were retrospectively reviewed. Patients with cerebrovascular accidents at GCA diagnosis were included. Diagnosis of GCA was based on American College of Rheumatology criteria. Transient ischemic attacks and stroke resulting from an atherosclerotic or cardioembolic mechanism were excluded. Clinical features, GCA-diagnosis workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data were analyzed. From January 2008 to January 2014, 97 patients have been followed for GCA. Among them, 8 biopsy-proven GCA patients (mean age 70±7.8 years, M/F sex ratio 3/1) had stroke at GCA diagnosis. Six patients reported headache and visual impairment. Brain MR angiography showed involvement of vertebral and/or basilar arteries in all cases with multiple or unique ischemic lesions in the infratentorial region of the brain in all but one case. Intracranial cerebral arteries involvement was observed in 4 cases including 2 cases with cerebral angiitis. Long lasting lesions on diffusion-weight brain MRI sequences were observed in 1 case. All patients received steroids for a mean of 28.1±12.8 months. Side effects associated with long-term steroid therapy occurred in 6 patients. Relapses occurred in 4 patients and required immunosuppressive drugs in 3 cases. After a mean follow-up duration of 36.4±16.4 months, all but 1 patient achieved complete remission without major sequelae. The conjunction of headache with vertebral and basilar arteries involvement in elderly is highly suggestive of stroke associated with GCA. Intracranial cerebral arteries involvement with cerebral angiitis associated with long lasting brain lesions on diffusion-weight brain MRI sequences may occur in GCA. Both frequent relapses and steroid-induced side effects argue for the use of immunosuppressive agents combined with steroids as first-line therapy.

High prevalence of deficient mismatch repair phenotype and the V600E BRAF mutation in elderly patients with colorectal cancer.

AIMS: Colorectal cancer (CRC) occurs mostly in the elderly. However, the biology of CRC in elderly has been poorly studied. This study examined the prevalence of deficient mismatch repair phenotype (dMMR) and BRAF mutations according to age. PATIENTS AND METHODS: MMR phenotype was prospectively determined by molecular analysis in patients of all ages undergoing surgery for CRC. BRAF V600E mutation status was analysed in a subset of dMMR tumours. RESULTS: A total of 754 patients who underwent surgery between 2005 and 2008 were included in the study. Amongst them, 272 (36%) were ≥75years old. The proportion of women <75 was 38% and that ≥75 was 53% (p<0.0001). The prevalence of dMMR was 19.4% in patients ≥75 and 10.7% in patients <75 (p=0.0017). For patients ≥75, the prevalence of dMMR was significantly higher in women than in men (27% vs 10.2%, respectively; p=0.003) but was similar in women and men <75 (12.5% vs 9.7%, respectively; p=0.4). We examined BRAF mutation status in 80 patients with dMMR tumours. The V600E BRAF mutation was significantly more frequent in patients ≥75 than in patients <75 (72.2% vs 11.4%, respectively; p<0.001). In patients ≥75, there was no difference in the prevalence of the BRAF V600E mutation according to sex (78% in women and 70% in men, p=0.9). CONCLUSIONS: The prevalence of dMMR in CRC is high in patients over 75. In elderly patients, dMMR tumours are significantly more frequent in women than in men. The BRAF mutation is frequent in elderly patients with CRC.

The learning curve of transrectal ultrasound-guided prostate biopsies: implications for training programs.

OBJECTIVE: To assess the quality of specimens obtained from prostate biopsies performed by urology residents and evaluate the number of procedures required to perform high-quality transrectal ultrasound (TRUS)-guided prostate biopsies. MATERIALS AND METHODS: Between 2006 and 2009, 770 patients underwent TRUS-guided prostate biopsies in our academic center. During the 6 semesters of this period, 24 residents (4 per semester) performed 1 session of 5.6±1.5 procedures each month for a total of 33.6±9 procedures during the study. The first session was performed with a senior urologist. Prostate cancer detection rate and standards of quality (average length of prostatic core biopsy specimens and absence of prostatic tissue) were retrospectively studied between the beginning and the end of each semester. RESULTS: A total of 12,760 biopsy cores were performed for 770 procedures. Mean patient age (64.5±6.1 years), and median prostate-specific antigen (8.7±3.7 ng/mL) were comparable between the study periods. The average length of biopsy cores significantly improved (+10%) from the first (12±2.7 mm) to the last month (13.2±2.1 mm) with a plateau after 12 procedures. Overall, cancer detection rate was 47% and was stable during the semester (41.3% the first month vs 44.1% the last month; P=.39). On univariate and multivariate analysis the mean length of biopsy specimens was associated with the number of procedures (P<.001) and the number of cores performed (P<.001). CONCLUSION: Twelve procedures are necessary to perform high-quality TRUS-guided prostate biopsies without compromising prostate cancer detection. In current training programs, we strongly recommend that residents have direct supervision for a minimum of 12 cases before they are allowed to perform TRUS-guided biopsies with indirect supervision.

Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients.

OBJECTIVE: About 15% of colorectal adenocarcinomas have a deficient DNA mismatch repair phenotype. The frequency of deficient DNA mismatch repair tumours increases with age due to the hypermethylation of hMLH1 promoter. The study aimed to determine the prognostic value of deficient DNA mismatch repair phenotype in elderly patients. DESIGN: Mismatch repair phenotype was retrospectively determined by molecular analysis in consecutive resected colorectal adenocarcinoma specimens from patients over 75 years of age from 4 Oncology centres. RESULTS: 231 patients (median age: 81, range: 75-100) were enrolled from 2005 to 2008. Mean prevalence of deficient DNA mismatch repair phenotype was 22.5%, and 36% for patients over 85 years. Deficient DNA mismatch repair status was significantly associated with older age, female sex, proximal colon primary and high grade tumour. For stage II tumours no deficient DNA mismatch repair tumours had a recurrence at end of follow-up compared to 17% for tumours with proficient phenotype. The proficient phenotype status was significantly associated with worse age-adjusted overall survival [HR 2.60; 95% CI 1.05-6.44; p=0.039]. For stage III tumours a trend for less recurrence was observed for deficient DNA mismatch repair phenotype (16%) compared to proficient phenotype (36%). CONCLUSION: deficient DNA mismatch repair phenotype is a prognostic factor in stage II colorectal tumour in elderly patients. Our results suggest that mismatch repair phenotype should be taken in consideration for adjuvant chemotherapy decision in elderly patients.

Management of adenocarcinoma of the female urethra: case report and brief review.

INTRODUCTION: We present a case of a differentiated adenocarcinoma of the female urethra, which caused dysuria and voiding dysfunction. MATERIALS AND METHODS: A 54-year-old female presented with dysuria and the sensation of incomplete voiding. RESULTS: An ultrasound-guided biopsy showed a urethral carcinoma. A magnetic resonance imaging (MRI) scan showed a high-stage tumor. The patient had a pelvic exenteration. The patient was free of disease after 2 years of follow up. CONCLUSION: Urethral carcinoma is a rare malignancy. A biopsy is necessary to make a diagnosis. MRI is the best imaging for tumor staging. Small tumors are treated with a single modality option including sparing surgery or radiotherapy. Advanced disease should be treated with a multimodality of options including neoadjuvant radiotherapy given concomitantly with chemotherapy followed by surgery.

Half of elderly patients routinely treated for colorectal cancer receive a sub-standard treatment.

BACKGROUND: Several database studies report a lack of care in elderly patients with colorectal cancer. PURPOSE: To describe the management of elderly patients admitted for colorectal cancer; to identify factors associated with standard management according to recommendations and to study factors influencing the survival. PATIENTS AND METHODS: All consecutive patients over 75 years managed for a colorectal adenocarcinoma in our hospital from 1995 to 2000 and followed until 2006 were retrospectively included. The appropriateness of the management of their disease according to the recommendations available at that time was assessed. Several risk factors in receiving the standard cancer treatment were tested using univariate and then multivariate logistic regression. Risk factors of survival were studied using univariate and then multivariate survival analysis. RESULTS: One hundred and ten patients were included. Median age was 82 years (range: 75-96). A surgical treatment was performed in 96 patients. The median overall survival was 32 (1-108) months. A standard cancer treatment according to recommendations was performed in 53 (48%) patients: adjuvant chemotherapy in 6/23 patients with stage III tumour, palliative chemotherapy in 3/18 patients with stage IV tumour and adjuvant radiotherapy in 4/14 patients who had a rectal tumour resection. Multivariate analysis retains tumour stage I or II (OR=7.6, 95% C.I.=[2.9-19.9], p<0.0001) as the only factor associated with standard treatment and presence of metastasis (HR=3.9, 95% C.I. [1.4-10.8], p=0.005), and Charlson's score >3 (HR=28.9, 95% C.I. [2.5-335.6], p=0.001) as independent risk factors of poor survival. CONCLUSIONS: Fifty two percent of elderly patients have had a sub-standard cancer treatment. The majority had a surgical treatment, but only a few received chemotherapy or radiotherapy. Metastasis, older age and Charlson's comorbidity score are the main prognosis factors of poor survival.

[The importance of controls in immunohistochemistry: how to validate an antibody, from research to diagnosis]. / Les contrôles nécessaires en immunohistochimie: de la recherche au diagnostic.

The specificity of an immunohistochemical reaction is guaranteed by two sets of controls. Positive controls verify the specificity of the primary antibody and demonstrate that it binds only to the protein which was used as an immunogen. Negative controls ensure that the labelling technique is specific and that the primary antibody is responsible for generation of the immunostaining. In fact, the production of a labelling may also be related to cross reactivity or to non-specific physical or chemical interactions. This paper reviews the characteristics of various epitopes and antibodies, describes different strategies which prove the specificity of the immunohistochemical reaction in research or diagnostic pathology and point towards the essential information which should be reported in a paper.