Citations

Study Design: Systematic review. Objective: Surgical decompression and reconstruction of symptomatic spinal metastases has improved the quality of life in cancer patients. However, most data has been collected on cohorts of patients with mixed tumor histopathology. We systematically reviewed the literature for prognostic factors specific to the surgical treatment of prostate metastases to the spine. Methods: A systemic review of the literature was conducted to answer the following questions: Question 1. Describe the survival and functional outcomes of surgery or vertebral augmentation for prostate metastases to the spine. Question 2. Determine whether overall tumor burden, Gleason score, preoperative functional markers, and hormonal naivety favor operative intervention. Question 3. Establish whether clinical outcomes vary with the evolution of operative techniques. Results: A total of 16 studies met the preset inclusion criteria. All included studies were retrospective series with a level of evidence of IV. Included studies consistently showed a large effect of hormone-naivety on overall survival. Additionally, studies consistently demonstrated an improvement in motor function and the ability to maintain/regain ambulation following surgery resulting in moderate strength of recommendation. All other parameters were of insufficient or low strength. Conclusions: There is a dearth of literature regarding the surgical treatment of prostate metastases to the spine, which represents an opportunity for future research. Based on existing evidence, it appears that the surgical treatment of prostate metastases to the spine has consistently favorable results. While no consistent preoperative indicators favor nonoperative treatment, hormone-naivety and high Karnofsky performance scores have positive effects on survival and clinical outcomes.

Background: In pediatric patients, pedicle screws are malpositioned 5% to 15% of the time. Complications associated with malpositioned screws are infrequently reported in the literature. We present a series of adolescent idiopathic scoliosis (AIS) patients who presented in a delayed manner with positional headache and chronic dural leak adjacent to the pedicle screw tract. Methods: Scoliosis databases at 2 centers were reviewed, and cases of delayed positional headaches following posterior spinal fusion for AIS were identified. Demographic and clinical data were collected. Results: Of 322 patients, 4 patients presented with positional headaches at a mean of 12.8 weeks following posterior spinal fusion surgery for AIS, with an interval time to diagnosis of 5 months. Computed tomographic myelogram demonstrated severe pedicle screw malposition in 1 patient, and minimal malposition in 3 patients (<2 mm violation). The patients had delayed presentation with positional headaches secondary to dural leak. All patients successfully underwent revision surgery with repair of the dural leak. At the time of latest follow-up, all patients are asymptomatic. Conclusions: Pedicle screw malposition can result in dural leaks. Patients may present in a delayed manner with positional headaches and an acquired Chiari malformation. Clinical suspicion should prompt imaging of the brain or cervical spine followed by computed tomographic myelogram to determine site of leak. This is a rare complication from pedicle screw malposition. Levels of Evidence: Level IV—case series.

Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 (non-V600 BRAF mutations). Methods We conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of non-V600 BRAF mutations in metastatic CRC. We pooled patients in whom non-V600 BRAF mutations were identified from NGS databases at three large molecular genetics reference laboratories. Results A total of 9,643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with non-V600 BRAF mutations, which occurred in 2.2% of all patients tested and accounted for 22% of all BRAF mutations identified. Cancers with non-V600 BRAF mutations, compared with cancers with V600E BRAF (V600E BRAF) mutations, were found in patients who were significantly younger (58 v 68 years, respectively), fewer female patients (46% v 65%, respectively), and patients who had fewer high-grade tumors (13% v 64%, respectively) or right-sided primary tumors (36% v 81%, respectively). Median overall survival was significantly longer in patients with non-V600 BRAF-mutant metastatic CRC compared with those with both V600E BRAF-mutant and wild-type BRAF metastatic CRC (60.7 v 11.4 v 43.0 months, respectively; P < .001). In multivariable analysis, non-V600 BRAF mutation was independently associated with improved overall survival (hazard ratio, 0.18; P < .001). Conclusion Non-V600 BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a clinically distinct subtype of CRC with an excellent prognosis.

Single-cell diversity in the brain The cells that make up an organism may all start from one genome, but somatic mutations mean that somewhere along the line of development, an organism's individual cellular genomes diverge. McConnell et al. review the implications and causes of single-cell genomic diversity for brain function. Somatic mutations caused by mobile genetic elements or errors in DNA repair may underlie certain neuropsychiatric disorders. Science , this issue p. eaal1641

Study Design: A multicenter, retrospective case series. Objective: In the past several years, screw fixation of the cervical spine has become commonplace. For the most part, this is a safe, low-risk procedure. While rare, screw backout or misplaced screws can lead to morbidity and increased costs. We report our experiences with this uncommon complication. Methods: A multicenter, retrospective case series was undertaken at 23 institutions in the United States. Patients were included who underwent cervical spine surgery from January 1, 2005, to December 31, 2011, and had misplacement of screws requiring reoperation. Institutional review board approval was obtained at all participating institutions, and detailed records were sent to a central data center. Results: A total of 12 903 patients met the inclusion criteria and were analyzed. There were 11 instances of screw backout requiring reoperation, for an incidence of 0.085%. There were 7 posterior procedures. Importantly, there were no changes in the health-related quality-of-life metrics due to this complication. There were no new neurologic deficits; a patient most often presented with pain, and misplacement was diagnosed on plain X-ray or computed tomography scan. The most common location for screw backout was C6 (36%). Conclusions: This study represents the largest series to tabulate the incidence of misplacement of screws following cervical spine surgery, which led to revision procedures. The data suggest this is a rare event, despite the widespread use of cervical fixation. Patients suffering this complication can require revision, but do not usually suffer neurologic sequelae. These patients have increased cost of care. Meticulous technique and thorough knowledge of the relevant anatomy are the best means of preventing this complication.

Study Design: Multi-institutional retrospective case series of 8887 patients who underwent anterior cervical spine surgery. Objective: Anterior decompression from discectomy or corpectomy is not without risk. Surgical morbidity ranges from 9% to 20% and is likely underreported. Little is known of the incidence and effects of rare complications on functional outcomes following anterior spinal surgery. In this retrospective review, we examined implant extrusions (IEs) following anterior cervical fusion. Methods: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of 21 predefined treatment complications. Results: Following anterior cervical fusion, the incidence of IE ranged from 0.0% to 0.8% across 21 institutions with 11 cases reported. All surgeries involved multiple levels, and 7/11 (64%) involved either multilevel corpectomies or hybrid constructs with at least one adjacent discectomy to a corpectomy. In 7/11 (64%) patients, constructs ended with reconstruction or stabilization at C7. Nine patients required surgery for repair and stabilization following IE. Average length of hospital stay after IE was 5.2 days. Only 2 (18%) had residual deficits after reoperation. Conclusions: IE is a very rare complication after anterior cervical spine surgery often requiring revision. Constructs requiring multilevel reconstruction, especially at the cervicothoracic junction, have a higher risk for failure, and surgeons should proceed with caution in using an anterior-only approach in these demanding cases. Surgeons can expect most patients to regain function after reoperation.

BACKGROUND. Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess. METHODS. We performed mass spectrometry–based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess. We also analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing adenoma, employing immunohistochemistry with digital image analysis. RESULTS. Primary aldosteronism patients had significantly increased cortisol and total glucocorticoid metabolite excretion (all P < 0.001), only exceeded by glucocorticoid output in patients with clinically overt adrenal Cushing syndrome. Several surrogate parameters of metabolic risk correlated significantly with glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression was significantly associated with the corresponding in vivo glucocorticoid excretion. Unilateral adrenalectomy resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in 13 (29%) of 45 consecutively tested patients. CONCLUSION. Our data indicate that glucocorticoid cosecretion is frequently found in primary aldosteronism and contributes to associated metabolic risk. Mineralocorticoid receptor antagonist therapy alone may not be sufficient to counteract adverse metabolic risk in medically treated patients with primary aldosteronism. FUNDING. Medical Research Council UK, Wellcome Trust, European Commission.

Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK‐2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK‐2206 in combination with BR in relapsed CLL. Single‐agent MK‐2206 (weekly dosed) was administered one‐week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2‐6. Phase II employed the MTD of MK‐2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6‐cycle of therapy. The maximum tolerated dose of MK‐2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial.