Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.     

Expression of minichromosome maintenance MCM6 protein in meningiomas is strongly correlated with histologic grade and clinical outcome

The 2007 World Health Organization histologic grading of meningiomas is associated with recurrence and clinical outcome. However, distinction of grade I from grade II (atypical) meningiomas can be challenging. In the World Health Organization classification, there are 4 parameters on the basis of which grade II status can be determined: mitotic rate, cytoarchitectural features, brain invasion, and/or histologic subtype. Furthermore, this classification fails to detect grade I recurrent meningiomas, for which other prognostic criteria would be needed. The aim of this study was to evaluate the respective value of several markers involved in cell cycle as effective tools to predict recurrence. This retrospective study was based on a series of 59 meningiomas (grade I: 32 of 59, grade II: 27 of 59, all harboring ≥4 mitoses/1.6 mm), analyzed with the following immunohistochemical markers: MCM6, Ki-67, PHH3, cyclin D1, and p53. We found a significant correlation between histologic grade and mean labeling index for MCM6 (grade I: 21.8% vs. grade II: 65.8%; P<0.001), Ki-67 (3.2% vs. 16.9%; P<0.001), PHH3 (0.7‰ vs. 2.8‰; P<0.001), cyclin D1 (50.4% vs. 70.0%; P=0.005), and p53 (17.3% vs. 32.4%; P=0.017). Histologic grading and mitotic index were correlated with progression-free survival (P=0.010 and P=0.020, respectively). A nearly linear correlation was found between progression-free survival and staining for MCM6 (P<0.001), Ki-67 (P=0.003), and PHH3 (P=0.037) but not for cyclin D1 (P=0.400) and p53 (P=0.758). The interobserver agreement coefficients for MCM6, Ki-67, PHH3, cyclin D1, and p53 were, respectively, 0.97 (95% confidence interval, 0.95-0.98), 0.93 (0.89-0.96), 0.81 (0.70-0.88), 0.90 (0.83-0.94), and 0.84 (0.73-0.90). In conclusion, because of its strong level of expression and sharp difference in labeling index between indolent and recurrent tumors, MCM6 is the most efficient marker to identify tumors with a high risk of recurrence.     

Functional hypoparathyroidism in postmenopausal women with fragility fracture

IntroductionSecondary hyperparathyroidism sometimes is lacking despite authentic vitamin D insufficiency (VDI) and the concept of functional hypoparathyroidism with a protective role on bone status has been proposed. Therefore, we tested the hypothesis that its prevalence was very low in a population of women with a peripheral fragility fracture.MethodsWe conducted our study in postmenopausal women, admitted for such a fracture in our Fracture Liaison Service. All had bone mineral density (BMD), biochemical assessment and a medical visit.ResultsTwo hundred and thirty seven women (72.9 ± 11.6-year-old) were included and 90.4% had VDI (25[OH]D ≤ 30 ng/mL). Yet, 87.9% of the latter had normal PTH levels less or equal to 64 ng/L. In this population with VDI (n = 214), we found no PTH plateau level related to 25(OH)D. Since a recent study reported an increase in the risk of fracture only when 25(OH)D was below 15 ng/mL, we then used this value as a new threshold. We observed a significant difference in hip BMD between patients with 25(OH)D either less or equal to or greater than 15 ng/mL. However, 81.2% of the formers were still with normal PTH with no difference in BMD whether PTH level was above or within normal range.ConclusionIn a population of postmenopausal women with a fragility fracture, we found that 25(OH)D less or equal to 15 ng/mL was associated with significantly lower hip BMD. Even using this low threshold, we found a high prevalence of functional hypoparathyroidism and it was not associated with any difference in hip or spine BMD. Overall, our results do not support the hypothesis of a protective effect of this biological profile.     

Screw impingement on the extensor tendons in distal radius fractures treated by volar plating: sonographic appearance

OBJECTIVE: The objective of our study was to analyze the sonography examinations of nine consecutive patients with a history of distal radius fracture treated by open reduction and internal fixation of the volar plate who were referred by hand surgeons for sonography of the dorsal aspect of the wrist. CONCLUSION: We postulate that impingement of the extensor tendons in patients with distal radius fracture treated by volar plating starts with local hyperemia and is followed by tenosynovitis and, finally, by partial and complete tendon tears. Sonography is an effective, dynamic, and noninvasive technique with which to diagnose and evaluate damage to the extensor tendons and their synovial sheaths.     

Case Report—Complex Management of a Postoperative Bronchogastric Fistula After Laparoscopic Sleeve Gastrectomy

Laparoscopic sleeve gastrectomy (LSG) is a new restrictive bariatric procedure increasingly indicated in the treatment of morbid obesity. Postoperative complications are mainly represented by gastric fistula with an occurrence rate of 0% to 5.1% in the literature. This complication is difficult to manage and requires multiple radiological, endoscopic, and surgical procedures. We report herein the case of a 23-year-old woman who underwent LSG for morbid obesity. This patient was reoperated for peritonitis due to a gastric fistula located on the top of the staple line. Five months later, she complained of a cough with fever and expectoration. A methylene blue test and a computed tomography scan diagnosed a postoperative bronchogastric fistula. After failure of aggressive conservative management, radical surgery was performed with total gastrectomy, reconstruction of the diaphragm using the extended latissimus dorsi flap, and a pulmonary lobectomy. This case report highlights the possible issue of the complex management of gastric fistula after LSG.     

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10‐year postrandomization follow‐up study

Long‐term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post‐transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients’ survival was 100%, 94.2%, and 95.8% (P = 0.25), and death‐censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m², respectively (P = 0.16). The incidence of biopsy‐proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus‐associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody‐mediated rejection (n = 6). De novo donor‐specific antibodies were detected in 13% of AZA‐, 21% of MMF‐, and 14% of CsA‐treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well‐selected renal transplant recipient ( ClinicalTrials.gov number: 980654).     

Gastric Stenosis After Laparoscopic Sleeve Gastrectomy: Diagnosis and Management

Purpose

The use of laparoscopic sleeve gastrectomy (LSG) is increasing worldwide. Although post-LSG gastric stenosis (GS) is less frequent, it has not been well defined and lacks standardized management procedures. The objective of the present study was to describe a series of patients with GS symptoms after LSG and to develop a standardized management procedure for this complication.

Methods

We performed a retrospective analysis of a prospective database of patients presenting with GS after LSG procedures performed between January 2008 and March 2014. The primary efficacy criterion was the frequency of post-LSG GS. GS was classified as functional (i.e. a gastric twist) or organic. The secondary efficacy criteria included the time interval between LSG and diagnosis of GS, the type of stenosis, the type of management, and the follow-up data.

Results

During the study period, 1210 patients underwent primary or secondary LSG. Seventeen patients had post-operative symptoms of GS (1.4 %); one patient had achalasia that had not been diagnosed preoperatively and thus was excluded from our analysis. The median time interval between LSG and diagnosis of GS was 47.2 days (1–114). Eleven patients had organic GS and six had functional GS. Seven patients required nutritional support. Endoscopic treatment was successful in 15 patients (88.2 %) after balloon dilatation (n?=?13) or insertion of a covered stent (n?=?2). Two of the 15 patients required conversion to Roux-en-Y gastric bypass (11.8 %).

Conclusion

GS after LSG is a rare complication but requires standardized management. Most cases can be treated successfully with endoscopic balloon dilatation.