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.     

Recurrence of Dislocation Following Total Hip Arthroplasty Revision Using Dual Mobility Cups Was Rare in 180 Hips Followed Over 7?Years

Background

Dual mobility (DM) cups of mobile polyethylene were introduced to prevent total hip arthroplasty (THA) dislocation, but no large series with this design to treat recurrent instability have been reported.

Purpose

Our retrospective investigation ascertained the efficiency of DM cups in correction of recurrent dislocation and assessed any adverse effects.

Methods

One hundred eighty THAs with recurrent instability were revised to DM cups in 180 patients (mean age, 67.4 ± 11.7 years; range, 19 to 92 years). Thirty-one patients (17.2%) underwent at least one earlier THA revision, and 15 (10.3%) incurred non-union of the greater trochanter. Of the initial group in 2009, 145 patients had completed evaluations which included assessment of the Harris Hip Score and a radiographic assessment at a mean follow-up of 7.7 ± 2.2 years (range, 4 to 14 years). The rate of survival was calculated considering any reason for revision as failure.

Results

At follow-up, Harris hip score was 83.9 ± 16.1 (range, 21 to 100). Dislocation of the large articulation occurred in seven hips (4.8%), and only two recurred (1.4%) (one requiring additional revision). In addition, two intra-prosthetic dislocations of the small articulation (1.4%) were observed and needed revision surgery. The large number of earlier surgeries and non-union of the greater trochanter were related to recurrent instability. Two cups (1.4%) showed signs of definite loosening; six (4.1%) presented signs of possible loosening. Twenty-nine hips manifested femoral or acetabular osteolysis (20%), but only three were severe. Eight-year survival rate considering revision for any reason was 92.6% (95% CI, 85.5–96.4%).

Conclusions

This series indicates that DM cups are a viable option to treat recurrent THA instability. Their design provides a low risk of recurrent instability without increasing mechanical complications.     

Traumatic hip dislocation in childhood

Traumatic dislocation of the hip in childhood is uncommon and can be a consequence of minor trauma. The authors report a series of 35 dislocations in skeletally immature patients. Most were isolated posterior dislocations without acetabular lesions. In 75% of cases, reduction of the dislocation was easy. Nine children required surgery to remove interposed joint capsule and/or osteochondral fragments to achieve anatomic reduction. Outcomes were generally good, except in one patient in whom a displaced fracture of the femoral physis was followed by total head avascular necrosis. One case of partial necrosis had a satisfactory outcome. Epiphyseal necrosis, though uncommon, appeared to be inconsistent to prevent and hard to predict. Bone scan seems to be more effective than MRI for the detection of necrosis.     

Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal rule

OBJECTIVE: To assess oncologic outcome of patients treated by conservative radical surgery for tumors below 5 cm from the anal verge. SUMMARY BACKGROUND DATA: Standard surgical treatment of low rectal cancer below 5 cm from the anal verge is abdominoperineal resection. METHODS: From 1990 to 2003, patients with a nonfixed rectal carcinoma at 4.5 cm or less from the anal verge and without external sphincter infiltration underwent conservative surgery. Surgery included total mesorectal excision with intersphincteric resection, that is, removal of the internal sphincter, to achieve adequate distal margin. Patients with T3 disease or internal sphincter infiltration received preoperative radiotherapy. RESULTS: Ninety-two patients with a tumor at 3 (range 1.5-4.5) cm from the anal verge underwent conservative surgery. There was no mortality and morbidity was 27%. The rate of complete microscopic resection (R0) was 89%, with 98% negative distal margin and 89% negative circumferential margin. In 58 patients with a follow-up of more than 24 months, the rate of local recurrence was 2% and the 5-year overall and disease-free survival were 81% and 70%, respectively. CONCLUSIONS: The technique of intersphincteric resection permits us to achieve conservative surgery in patients with a tumor close to or in the anal canal without compromising local control and survival. Tumor distance from the anal verge is no longer a limit for sphincter-saving resection.     

Residual motion of cortical versus pedicle screw constructs after decompression,interbody fusion and cross-link augmentation

Purpose

To compare the residual range of motion (ROM) of cortical screw (CS) versus pedicle screw (PS) instrumented lumbar segments and the additional effect of transforaminal interbody fusion (TLIF) and cross-link (CL) augmentation.

Methods

ROM of thirty-five human cadaver lumbar segments in flexion/extension (FE), lateral bending (LB), lateral shear (LS), anterior shear (AS), axial rotation (AR), and axial compression (AC) was recorded. After instrumenting the segments with PS (n = 17) and CS (n = 18), ROM in relation to the uninstrumented segments was evaluated without and with CL augmentation before and after decompression and TLIF.

Results

CS and PS instrumentations both significantly reduced ROM in all loading directions, except AC. In undecompressed segments, a significantly lower relative (and absolute) reduction of motion in LB was found with CS 61% (absolute 3.3°) as compared to PS 71% (4.0°; p = 0.048). FE, AR, AS, LS, and AC values were similar between CS and PS instrumented segments without interbody fusion. After decompression and TLIF insertion, no difference between CS and PS was found in LB and neither in any other loading direction. CL augmentation did not diminish differences in LB between CS and PS in the undecompressed state but led to an additional small AR reduction of 11% (0.15°) in CS and 7% (0.05°) in PS instrumentation.

Conclusion

Similar residual motion is found with CS and PS instrumentation, except of slightly, but significantly inferior reduction of ROM in LB with CS. Differences between CS and PS in diminish with TLIF but not with CL augmentation.

     

Early effects of nucleus pulposus application on spinal nerve root morphology and function

It is known that 24 h or more after epidural application of autologous nucleus pulposus, functional and structural changes are established in adjacent nerve roots. It is, however, not known how soon after the application these changes appear. The aim of this study was to reduce the exposure duration to 3 h and to evaluate nerve function and histological changes in the nerve tissue during this time period. A total of 12 pigs was used. In ten pigs, autologous nucleus pulposus (NP) was applied epidurally on the cauda equina. Nerve function was then monitored for 3 h by measurements of muscle action potentials (MAP) in the tail muscles, following nerve root stimulation cranial to the exposed zone. In five of the ten pigs with NP application, nerve root compression to 50 mm Hg was added by means of an inflatable balloon. In two control animals, neither NP nor compression was applied. At the end point, nerve root specimens were harvested for histological assessment. No reduction of MAP amplitude was detected in any of the series. However, there was an epidural accumulation of leucocytes and mast cells, as well as minor axonal and Schwann cell changes in both the NP and NP+ compression series, as compared to the control series. Morphological changes in terms of an epidural inflammatory reaction and minor axonal and Schwann cell damage may thus be demonstrated within 3 h of NP application, with or without compression. However, there is no functional deterioration of the nerve roots detectable within this time period. Received: 19 February 1998 Revised: 26 June 1998 Accepted: 8 July 1998     

Early reduction versus skin traction in the orthopaedic treatment of femoral shaft fractures in children under 6 years old

Background  Femoral shaft fractures occur very frequently in children, and their prognosis usually is good. Nonoperative treatment is the gold standard for children under 6 years because of the excellent bony union and the remodelling qualities. Purpose  The aim of this study was to compare two orthopaedic therapeutic methods: skin traction versus immediate reduction. Materials and methods  The study involved 35 children, divided into two groups: in group 1, treatment consisted of skin traction for 21 days followed by hip spica casting; in group 2, an immediate reduction with early hip spica casting was performed. The ranges of motion, the delay before weight bearing, the hospitalisation duration and the required amount of painkillers were recorded. We compared initial shortening, axial, sagittal and rotational alignment, and femoral length discrepancy. We calculated the injured femoral diaphysal overgrowth and correlated it to the fracture type and location and to the initial shortening. Economical variables were also studied. Results  The mean overgrowth was 8.9 mm in group 1 and 8.5 mm in group 2. Three years after the trauma, length discrepancy was 4 mm in group 1 and 1 mm in group 2. Hip spica casting leads to significant reductions in weight-bearing delay, hospitalisation duration and pain. The cost of treatment with skin traction was four times higher (24,472 euros) than that of immediate reduction (6,384 euros). Discussion  Our results are in accordance with the literature. The femoral overgrowth was proportional to the initial shortening. Masculine gender, an oblique fracture and injury of the lower third of the femur were associated with the greatest femoral overgrowth. During the first year of follow-up, the femoral length discrepancy hardly varied after immediate reduction (4 mm), whereas the overgrowth reached 6 mm after skin traction. Overall, immediate hip spica casting leads to significant reductions in weight-bearing delay, hospitalisation duration, complications and costs, while having similar clinical results as traction.