Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high‐risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta‐analysis (3940 melanoma cases and 3620 controls) with two‐side p values of 0.002, (OR = 0.86) and 4.07 × 10^?10 (OR = 0.80), respectively. Exome sequencing revealed a non‐synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma.     

Robot-assisted laparoscopic nephron sparing surgery for tumors over 4 cm: Operative results and preliminary oncologic outcomes from a multicentre French study

Objective

To assess operative and pathological results obtained after robot-assisted partial nephrectomy (RAPN) in renal masses over 4 cm.

Patients and methods

Between 2007 and 2011, 220 robotic nephron-sparing surgeries (NSS) were performed at six French urology departments. Data were prospectively collected: age, BMI, pre and post-operative eGFR (MDRD), operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), length of hospital stay (LOS), Clavien complications, pathological results and oncologic outcome. Tumor complexity was assessed according to the RENAL nephrometry score.

Results

Overall, 54 tumors were included. Median follow up was 26 months. Median age at surgery was 62 years. Median RENAL nephrometry score was 7 (4–10). Median WIT was 23 min (10–59). Median OT and EBL were 180 min (110–425) and 100 cc (0–2500). Blood transfusion occurred in 7 cases (13%). Median tumor size was 45 mm (40–70). Three patients had positive surgical margins. Median LOS was 5 days (2–28). Nine patients presented post-operative complications of which 1/3 were considered as major (Clavien IIIb). Median pre-operative and post-operative eGFR was 88 (36–136) and 75 ml/min (33–122) (p = 0.01), respectively. Two patients developed subsequent metastasis. The 2-year progression free survival (PFS) rate was 90.5%.

Conclusion

Our results confirm that RAPN is a useful and acceptable approach for renal masses greater than 4 cm in size. When technically possible, NSS provides promising short-term cancer-specific survival rates with acceptable morbidity. Tumor size is not sufficiently discriminant enough and RENAL nephrometry score should increasingly used to describe tumor complexity.     

Peritoneal amyloidosis: unusual localization of gastrointestinal amyloidosis

Amyloidosis is a rare disease that results from the extracellular deposition of amorphous fibrillar protein. It is usually observed in a systemic form. Gastrointestinal involvement is frequent but peritoneal localization is unusual. A 43-year-old male was investigated for nephritic colic. Morphologic explorations revealed small intestine agglomerans in the periumbilical region, infiltration of peritoneal fat and multiple coelio-mesenteric lymph nodes. There were no clinical or biological abnormalities and endoscopic examinations were normal. The patient then underwent an exploratory laparoscopy. Macroscopically false membranes were seen throughout the peritoneum and small bowel without ascites. Anatomopathologic examination diagnosed peritoneal amyloidosis. After several investigations a diagnosis of a primary peritoneal amyloidosis was confirmed. The patient was treated with melphalan and prednisone with a favorable outcome. Our case illustrates a particular presentation of peritoneal amyloidosis. Despite improved imaging methods, peritoneal biopsy remains essential for diagnosis.     

Evidence of human papillomavirus in the placenta

Human papillomavirus (HPV) is an epitheliotropic virus typically infecting keratinocytes but also possibly epithelial trophoblastic placental cells. In the present study, we set out to investigate whether HPV can be recovered from transabdominally obtained placental cells to avoid any confounding contamination by HPV-infected cervical cells. Thirty-five placental samples from women undergoing transabdominal chorionic villous sampling were analyzed, and we detected HPV-16 and HPV-62 in 2 placentas. This study suggests that HPV infection of the placenta can occur early in pregnancy. The overall clinical implication of these results remains to be elucidated.     

Giant hydatid lung cysts: About two paediatric cases

Cystic echinococcosis, which commonly starts during childhood or adolescence, is a serious problem of public health in Tunisia. The resulting large cysts in the lung are a special clinical entity called giant hydatid cysts. Herein we present two paediatric cases of this rare entity. In the first case a fourteen-year-old boy presented with chest pain, thoracic deformation, weight loss and dyspnea revealing two giant hydatid cysts of the upper and the lower lobes of the right lung. In the second case, a seven-year-old girl presented with chest pain, dyspnea, fever and episodes of suffocation revealing a giant hydatid cyst of the right upper lobe of the lung.The three giant cysts were non-complicated, they were treated by cystotomy and capitonnage without post-operative complications and without recurrence of the disease on follow-up.