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1.
Shoulder Elbow ; 15(3 Suppl): 54-59, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37974649

ABSTRACT

Introduction: As the prevalence of sleep apnea (SA) increases nationwide, large sample sized studies following primary reverse shoulder arthroplasty (RSA) in SA patients are scarce. Therefore, this study evaluated whether SA is associated with 1) longer in-hospital lengths of stay (LOS) 2) readmissions 3) medical complications and 4) costs. Methods: A retrospective nationwide Medicare analysis from 2005 to 2014 was performed. Inclusion criteria were patients with SA undergoing RSA for the treatment of glenohumeral osteoarthritis. Study group patients were 1:5 ratio matched to controls yielding 6241 patients in the study and 31,179 in the comparison cohort. Logistic regression was used to calculate odds-ratios (OR) for readmissions and complications. A p-value less than 0.004 was significant. Results: SA patients had significantly longer in-hospital LOS compared to their counterparts (3-days versus 2-days, p < 0.0001), but similar rates of 90-day readmissions (7.98% vs. 6.54%; OR: 1.00, p = 0.907). Patients with SA had significantly greater incidence and odds of 90-day medical complications (13.36% vs. 7.29%; OR: 1.42, p < 0.0001) and significantly higher 90-day costs ($16,529.16 vs. $14,789.15, p < 0.0001). Conclusion: Patients with SA undergoing primary RSA for the treatment of glenohumeral OA have longer in-hospital LOS, increased medical complications, and costs of care. Readmissions were not more common. Level of Evidence: III.

2.
Eur J Orthop Surg Traumatol ; 33(4): 883-888, 2023 May.
Article in English | MEDLINE | ID: mdl-35147770

ABSTRACT

PURPOSE: The incidence of proximal humerus fractures (PHF) is rising and surgical intervention carries risk for fracture nonunion. The purpose was (1) to compare patient demographics of those that developed nonunion and (2) identify patient risk factors that predispose to nonunion following open reduction and internal fixation (ORIF) for PHF. METHODS: A retrospective review of the Medicare Claims Database from 2005 to 2014 for patients who underwent primary ORIF for PHFs. Patients who developed nonunion were identified as the study group (n = 1020) and compared to a control group (n = 51,209). Primary endpoints were to compare demographics of the study group and the comparison cohorts and to identify patient-related risk factors associated with nonunion within 6-months following the index procedure. A logistic regression model was constructed to determine the association of comorbid conditions on developing a nonunion. A p value of 0.001 was the significance threshold. RESULTS: Patients who developed nonunion were younger, more likely to be male, and had higher Elixhauser-Comorbidity Index scores (7 vs. 5; p < 0.0001) when compared with controls. Iron deficiency anemia (OR: 1.32; p = 0.0001), tobacco use (OR: 1.32; p = 0.0004), rheumatoid arthritis (OR: 1.29; p = 0.0001), depression (OR: 1.28; p = 0.0002), and BMI range from 30-39 kg/m2 (OR: 1.21; p = 0.001) were significant risk factors for nonunion. CONCLUSIONS: Certain patient risk factors including tobacco use, iron deficiency anemia, rheumatoid arthritis, depression, and a BMI in the range of 30-39 were associated with nonunion within 6 months of ORIF for PHF. This study may help in the risk stratification of these patients.


Subject(s)
Anemia, Iron-Deficiency , Arthritis, Rheumatoid , Humeral Fractures , Shoulder Fractures , United States , Humans , Male , Aged , Female , Anemia, Iron-Deficiency/etiology , Fracture Fixation, Internal/methods , Medicare , Shoulder Fractures/surgery , Retrospective Studies , Risk Factors , Humeral Fractures/surgery , Treatment Outcome , Humerus/surgery
3.
Hand (N Y) ; 18(6): 1019-1026, 2023 09.
Article in English | MEDLINE | ID: mdl-35118899

ABSTRACT

BACKGROUND: Anemia is a modifiable risk factor that may influence postoperative complications following orthopedic surgical procedures. The objective was to determine the influence of preoperative anemia severity on postoperative complications and length of stay (LOS) following total elbow arthroplasty (TEA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program registry was queried from 2006 to 2019 for patients undergoing primary TEA. Using the World Health Organization definitions of anemia, patients undergoing TEA were stratified into 3 cohorts: nonanemia (hematocrit >36% for women, >39% for men), mild anemia (hematocrit 33%-36% for women, 33%-39% for men), and moderate-to-severe anemia (hematocrit <33% for both women and men). Patient demographics, surgical time, LOS, and postoperative complications were compared between the groups. A P value <.004 was considered significant. RESULTS: After exclusion, 589 patients, of whom 369 (62.6%) did not have anemia, 129 (21.9%) had mild anemia, and 91 (15.5%) had moderate/severe anemia, were included. Increasing severity of anemia was associated with an increased average hospital LOS (2.30 vs 2.81 vs 4.91 days, P < .001). There was a statistically significant increase in blood transfusions (1.08% vs 7.75% vs 17.58%, P < .001), major complications (9.21% vs 17.83% vs 34.07%, P < .001), any complications (11.11% vs 23.26% vs 36.26%, P < .001), and extended LOS ≥6 days (6.23% vs 6.98% vs 31.87%, P < .001) with increasing severity of anemia. Multivariate analysis identified moderate-to-severe anemia was significantly associated with major complications and extended LOS (P < .001). CONCLUSIONS: Preoperative anemia is a modifiable risk factor for medical and surgical complications within 30 days of TEA.


Subject(s)
Anemia , Elbow , Male , Humans , Female , Length of Stay , Anemia/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Arthroplasty/adverse effects
4.
Eur J Orthop Surg Traumatol ; 33(5): 1773-1779, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35951116

ABSTRACT

INTRODUCTION: Studies have shown male sex to be a predisposing factor for peri-prosthetic joint infections (PJIs). Symptomatic benign prostatic hyperplasia (BPH) has been suggested as an additional risk for PJI. This study aimed to assess the impact of BPH on (1) lengths of stay (LOS), (2) complications (medical and implant-related), (3) readmission rates, and (4) healthcare expenditures after reverse shoulder arthroplasty (RSA). METHODS: Utilizing a nationwide sample from the 2010-2020 PearlDiver insurance database, an analysis was performed retrospectively for all males who underwent primary RSA. Males with BPH (n = 2,184) represented the study group and were ratio-matched with men without a history of BPH (n = 10,832) in a 1:5 manner by medical comorbidities. T-tests compared LOS and healthcare expenditures. Multivariate logistic regression models were used to determine the effect of BPH on 90-day medical complications, 2-year implant complications, and readmissions. A p value less than 0.001 was statistically significant. RESULTS: In-hospital LOS (1.96 days vs. 1.99 days, p = 0.683) did not significantly differ between cohorts. Males with BPH had significantly greater occurrence and odds (34.3% vs. 21.2%, odds ratio (OR):1.84, p < 0.0001) of all 90-day medical complications, including urinary tract infections (9.3% vs. 3.1%, OR:3.23, p < 0.0001), pneumonias (6.0% vs. 3.9%, OR:1.61, p < 0.0001), and acute kidney injuries (7.7% vs. 5.0%, OR:1.60, p < 0.0001). Two-year implant-related complications were comparable between study and control groups (12.2% vs 10.9%, OR:1.14, p = 0.073), including PJIs (2.3% vs. 2.2%, OR:1.02, p = 0.874). Readmission rates (1.88% vs. 2.11%, p = 0.482) and average global 90-day reimbursements ($26,301 vs. $24,399), p = 0.535) were similar between men with and without BPH. DISCUSSION: Males with a history of BPH have greater rates of medical complications, including UTIs and acute kidney injuries, within 90 days following RSA. BPH does not appear to be a risk factor for 2-year implant-related complications including PJIs. LEVEL OF EVIDENCE: III.


Subject(s)
Arthroplasty, Replacement, Shoulder , Prostatic Hyperplasia , Urinary Tract Infections , Humans , Male , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/surgery , Retrospective Studies , Arthroplasty, Replacement, Shoulder/adverse effects , Arthroplasty/adverse effects , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Risk Factors , Urinary Tract Infections/epidemiology , Urinary Tract Infections/etiology
5.
J Wrist Surg ; 11(5): 433-440, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36339070

ABSTRACT

Background Complications after open reduction internal fixation (ORIF) for distal radius fractures (DRF) are well documented, but the impact of trainee involvement on postoperative outcomes has not been studied. Questions Does trainee involvement affect postoperative complication rates and length of hospital stay? Methods The American College of Surgeons National Surgical Quality Improvement Program was queried from 2006 to 2012 for patients undergoing DRF ORIF. A 1:1 propensity score matched resident/fellow involved cases to attending-only cases. Demographics, length of stay, and postoperative complications were compared between the two groups. Logistic regression was used to evaluate independent predictors of adverse events and to evaluate cases with and without trainee involvement. Results Overall, 3,003 patients underwent DRF ORIF from 2006 to 2012. After matching, 1,150 cases (50% with resident/fellow involvement) were included. The overall rate of adverse events was 4.4% (46/1,050). There were no significant differences in the short-term complication rate in trainee-involved (2.3%) versus attending-only cases (3.9%) ( p = 0.461). For ORIF of DRF, there were no significant differences, between attending-only cases and resident/fellow-involved cases, with regard to short-term major complications ( p = 0.720) or minor complications ( p = 0.374). Length of hospital stay was similar between cohorts (1.22 vs. 0.98 days) ( p = 0.723). On multivariate analysis, trainee involvement was not an independent predictor of minor, major, or any complication after DRF fixation after controlling for multiple independent factors (all p > 0.364). Discussion Trainee participation in DRF ORIF is not associated with increased risk of short-term (30 days) medical or surgical postoperative complications. Level of Evidence This is a Level IV case-control study.

6.
Bull Hosp Jt Dis (2013) ; 80(2): 228-233, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35643490

ABSTRACT

Bulletin of the Hospital for Joint Diseases 2022;80(2):228-33228 Mahmood B, Golub IJ, Ashraf AM, Ng MK, Vakharia RM, Choueka J. Risk factors for infections following open reduction and internal fixation for distal radius fractures: an analysis of the medicare claims database. Bull Hosp Jt Dis. 2022;80(2):228-33. Abstract Background: Infections following open reduction and internal fixation (ORIF) of distal radius fractures (DRFs) are associated with worse outcomes and increasing health care costs. The purpose of this study was to utilize a nationwide administrative claims database to compare patient demo- graphics of patients who did and did not develop infections and identify patient-related risk factors for postoperative infections. METHODS: Using the PearlDiver database, the 100% Medicare Files from 2005 to 2014 were queried. Patients undergoing ORIF for DRF were identified using Current Procedural Terminology (CPT) codes. Inclusion for the study group consisted of patients who developed infection within 90 days after the procedure and were identified us- ing CPT and International Classification of Disease, Ninth Revision (ICD-9) codes. Multivariable binomial logistic regression analyses were performed to calculate the odds (OR) of certain patient comorbidities and their association with infection following ORIF of DRFs. A p-value less than 0.002 was considered statistically significant after Bonfer- roni correction. RESULTS: The query yielded 132,650 patients within the study, 456 who developed surgical site infections (SSI) and 132,194 who did not. Surgical site infections were more commonly found in certain demographics, such as patients under the age of 65 (26.75 vs. 14.73%) and in males (20.83 vs. 14.15%). Multivariate regression analysis further highlighted that certain comorbidities increased odds for infections within 90-days following ORIF for distal radius fractures and those included: morbid obesity (OR: 2.06, p < 0.0001), depression (OR: 1.92, p = 0.0002), and pathologic weight loss (OR: 1.49, p = 0.001). CONCLUSION: The study found statistically significant dif- ferences between patients who developed and did not develop infection. These findings may help orthopedic surgeons to educate certain high-risk patients of the potential complica- tions that may occur following surgery.


Subject(s)
Radius Fractures , Aged , Animals , Cattle , Humans , Male , Medicare , Open Fracture Reduction/adverse effects , Radius Fractures/complications , Radius Fractures/surgery , Risk Factors , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , United States/epidemiology
7.
Shoulder Elbow ; 14(3): 278-285, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35599711

ABSTRACT

Background: Chronic obstructive pulmonary disease patients have been shown in orthopedic literature to have poorer outcomes and higher rates of complications from surgery. In this retrospective review, medical complications, length of stay, and costs were obtained to explore the effects of chronic obstructive pulmonary disease on patients undergoing primary total shoulder arthroplasty. Methods: Total shoulder arthroplasty cases from January 2005 to March 2014 were queried and analyzed from a nationwide database. Study patients were matched 1:5 to controls by age, sex, and medical comorbidities associated with chronic obstructive pulmonary disease. In-hospital length of stay, 90-day medical complications, day of surgery, and total global 90-day episode of care costs were obtained for comparison. Results: Chronic obstructive pulmonary disease patients were found to have higher incidence and odds (53.91 vs. 11.95%; OR: 3.58, 95%CI: 3.18-3.92, p < 0.0001) of 90-day medical complications, longer in-hospital length of stay (3 vs. 2 days, p < 0.0001), and significantly higher 90-day costs ($14,768.37 vs. $13,379.20, p < 0.0001) following primary total shoulder arthroplasty compared to matched controls. Discussion: Chronic obstructive pulmonary disease patients undergoing primary total shoulder arthroplasty have higher rates of medical complications, in-hospital length of stay, and costs of care. This represents an important factor that will allow orthopedic surgeons to adequately manage expectations and educate chronic obstructive pulmonary disease patients of the potential complications which may occur following total shoulder arthroplasty.

8.
Eur J Orthop Surg Traumatol ; 32(6): 1105-1110, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34351512

ABSTRACT

INTRODUCTION: The World Health Organization (WHO) postulates that depressive disorders (DD) will be the leading cause of morbidity and mortality by 2030. Studies evaluating the association of DD following open reduction and internal fixation (ORIF) for the treatment of acetabular fractures are limited. Therefore, the purpose of this matched-control study was to determine whether DD patients undergoing ORIF for acetabular fractures have higher rates of: (1) in-hospital lengths of stay (LOS); (2) readmissions; (3) medical complications; and (4) costs of care. MATERIALS AND METHODS: A retrospective query from the 100% Medicare Standard Analytical Files (SAF) was performed to identify patients who underwent ORIF for acetabular fractures. The study group consisted of those patients with DD, whereas patients without the condition served as controls. Primary endpoints of the study were to compare in-hospital LOS, readmission rates, ninety-day medical complications, and costs of care. A p-value less than 0.01 was considered statistically significant. RESULTS: The query yielded 7084 patients within the study (ORIF = 1187, control = 5897). DD patients were found to have significantly longer in-hospital LOS (11 days vs. 10 days, p < 0.0001); however, odds (OR) of readmission rates were similar (23.16 vs. 18.68%; OR: 0.91, p = 0.26). Multivariate regression demonstrated DD to be associated with significantly higher (67.69 vs. 25.54%; OR: 2.64, p < 0.0001) 90-day medical complications. DD patients had significantly higher day of surgery ($30,505.93 vs. $28,424.85, p < 0.0001) and total global 90-day costs ($41,721.98 vs. $37,330.16, p < 0.0001) of care. CONCLUSION: After adjusting for covariates, DD is associated with longer in-hospital, complications, and costs of care in patients undergoing ORIF for the treatment of acetabular fractures, whereas readmission rates are similar. The study is vital as it can be used by orthopaedists and healthcare professionals to adequately educate these patients of the potential outcomes following their surgical procedure.


Subject(s)
Depressive Disorder , Hip Fractures , Spinal Fractures , Aged , Depressive Disorder/etiology , Fracture Fixation, Internal/methods , Hip Fractures/surgery , Humans , Medicare , Open Fracture Reduction/adverse effects , Open Fracture Reduction/methods , Retrospective Studies , Spinal Fractures/etiology , Treatment Outcome , United States/epidemiology
9.
Cureus ; 13(6): e16059, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34354875

ABSTRACT

Hangman's fracture or traumatic spondylolisthesis of the axis is a common fracture pattern in the cervical spine. Nonoperative management with an external orthosis is appropriate in select cases. However, when surgery is necessary, both anterior and posterior approaches can be used, and the optimal approach has not been established. Anterior discectomy and fusion with plating at C2-3 may cause dysphagia from plate prominence, while the posterior fusion of C1-3 eliminates motion of an otherwise healthy atlantoaxial joint, resulting in a significant loss of cervical range of motion. We describe the first published application of a stand-alone, zero-profile implant at the C2-3 segment to treat Hangman's fracture, a technique already successfully used in the C3-7 region for trauma and degenerative applications. A stand-alone, zero profile interbody spacer was employed in anterior C2-3 arthrodesis surgery for Hangman's fracture in a 61-year-old female following failure of healing after three months in a hard cervical collar. Late postoperative imaging showed successful fusion and the patient had favorable clinical results with relief of neck pain. A zero-profile, stand-alone implant at C2/3 is an attractive option to surgically treat C2 Hangman's fracture, potentially minimizing dysphagia attributable to an anterior plate and spare the atlantoaxial joint that is fused with C1-3 posterior arthrodesis. The benefits of the application of this technique may be validated with additional studies.

10.
J Orthop ; 24: 186-189, 2021.
Article in English | MEDLINE | ID: mdl-33737792

ABSTRACT

INTRODUCTION: The purpose of this study was to determine whether alcohol use disorder (AUD) patients undergoing reverse shoulder arthroplasty (RSA) have increased: 1) lengths of stay (LOS); 2) complications; and 3) costs. METHODS: The study identified 19,168 patients in the study (n = 3198) and control (n = 15,970) cohort. In-hospital LOS, 90-day complications, and costs were assessed. RESULTS: AUD patients had significantly longer LOS (3- vs. 2-days, p < 0.0001), higher9 0-day medical complications (49.59 vs. 14.81%; p < 0.0001), and 90-day costs of care ($18,763.25 vs. $16,035.49, p < 0.0001). CONCLUSIONS: The study is useful as it can allow healthcare professionals to adequately counsel these patients.

11.
J Neurosci Methods ; 303: 68-80, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29454014

ABSTRACT

BACKGROUND: Second Harmonic Generation (SHG) microscopy is a promising method for visualizing the collagenous structure of peripheral nerves. Assessing collagen continuity and damage after a stretch injury provides inferential insight into the level of axonal damage present. NEW METHODS: This study utilizes SHG microscopy after a calibrated in vivo stretch injury of rat median nerves to evaluate collagen continuity at several time points throughout the recovery process. Endoneurial collagen was qualitatively assessed in nerves that were subjected to low strain (LS) and high strain (HS) injuries using SHG microscopy, conventional histology, and immunohistochemistry. RESULTS: Following an in vivo stretch injury, both LS and HS damaged nerves exhibit signs of structural collagen damage in comparison with sham control nerves (SC). Furthermore, LS nerves exhibit signs of full regeneration while HS nerves exhibited signs of only partial regeneration with lasting damage and intra-neural scar formation. COMPARISON WITH EXISTING METHODS: SHG observations of structural changes and inflammatory response due to stretch injury were validated upon comparison with conventional histological methods CONCLUSIONS: We propose that SHG microscopy can be utilized to visualize significant structural artifacts in sectioned median nerves following in vivo stretch injury. Based on the findings in this study, we believe that the in vivo application of SHG microscopy should be further investigated as a means for real-time, intra-operative, quantitative assessment of nerve damage.


Subject(s)
Collagen , Median Nerve/diagnostic imaging , Nerve Regeneration , Peripheral Nerve Injuries/diagnostic imaging , Second Harmonic Generation Microscopy/methods , Wallerian Degeneration/diagnostic imaging , Animals , Female , Median Nerve/immunology , Median Nerve/injuries , Median Nerve/pathology , Peripheral Nerve Injuries/immunology , Peripheral Nerve Injuries/pathology , Rats , Rats, Sprague-Dawley
12.
J Clin Oncol ; 34(18): 2141-7, 2016 06 20.
Article in English | MEDLINE | ID: mdl-27022117

ABSTRACT

PURPOSE: Tumor screening for Lynch syndrome is recommended in all or most patients with colorectal cancer (CRC). In metastatic CRC, sequencing of RAS/BRAF is necessary to guide clinical management. We hypothesized that a next-generation sequencing (NGS) panel that identifies RAS/BRAF and other actionable mutations could also reliably identify tumors with DNA mismatch repair protein deficiency (MMR-D) on the basis of increased mutational load. METHODS: We identified all CRCs that underwent genomic mutation profiling with a custom NGS assay (MSK-IMPACT) between March 2014 and July 2015. Tumor mutational load, with exclusion of copy number changes, was determined for each case and compared with MMR status as determined by routine immunohistochemistry. RESULTS: Tumors from 224 patients with unique CRC analyzed for MMR status also underwent MSK-IMPACT. Thirteen percent (n = 28) exhibited MMR-D by immunohistochemistry. Using the 341-gene assay, 100% of the 193 tumors with < 20 mutations were MMR-proficient. Of 31 tumors with ≥ 20 mutations, 28 (90%) were MMR-D. The three remaining tumors were easily identified as being distinct from the MMR-D tumors with > 150 mutations each. Each of these tumors harbored the P286R hotspot POLE mutation consistent with the ultramutator phenotype. Among MMR-D tumors, the median number of mutations was 50 (range, 20 to 90) compared with six (range, 0 to 17) in MMR-proficient/POLE wild-type tumors (P < .001). With a mutational load cutoff of ≥ 20 and < 150 for MMR-D detection, sensitivity and specificity were both 1.0 (95% CI, 0.93 to 1.0). CONCLUSION: A cutoff for mutational load can be identified via multigene NGS tumor profiling, which provides a highly accurate means of screening for MMR-D in the same assay that is used for tumor genotyping.


Subject(s)
Brain Neoplasms/diagnosis , Colorectal Neoplasms/genetics , High-Throughput Nucleotide Sequencing/methods , Mutation , Neoplastic Syndromes, Hereditary/diagnosis , Adolescent , Adult , Aged , Colorectal Neoplasms/diagnosis , Humans , Middle Aged
13.
JAMA Oncol ; 2(1): 104-11, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26556299

ABSTRACT

IMPORTANCE: Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. OBJECTIVE: To estimate the burden of germline variants identified through routine clinical tumor sequencing. DESIGN, SETTING, AND PARTICIPANTS: Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. MAIN OUTCOMES AND MEASURES: The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. RESULTS: The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99.9%; 95% CI, 99.6%-99.9%). CONCLUSIONS AND RELEVANCE: Germline variants are common in individuals undergoing tumor-normal sequencing and may reveal otherwise unsuspected syndromic associations.


Subject(s)
Biomarkers, Tumor/genetics , DNA Mutational Analysis/methods , Gene Expression Profiling/methods , Germ-Line Mutation , Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Models, Genetic , Neoplasms/pathology , Neoplasms/therapy , New York City , Phenotype , Precision Medicine , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors
14.
Cancer ; 121(24): 4382-8, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26440929

ABSTRACT

BACKGROUND: Pancreatic adenocarcinoma (PAC) is part of several cancer predisposition syndromes; however, indications for genetic counseling/testing are not well-defined. In the current study, the authors sought to determine mutation prevalence and characteristics that are predictive of an inherited predisposition for PAC. METHODS: A total of 175 consecutive patients with PAC who underwent clinical genetics assessment at Memorial Sloan Kettering Cancer Center between 2011 and 2014 were identified. Clinical data, family history, and germline results were evaluated. RESULTS: Among 159 patients with PAC who pursued genetic testing, 24 pathogenic mutations were identified (15.1%; 95% confidence interval, 9.5%-20.7%), including BRCA2 (13 mutations), BRCA1 (4 mutations), p16 (2 mutations), PALB2 (1 mutation), and Lynch syndrome (4 mutations). BRCA1/BRCA2 prevalence was 13.7% in Ashkenazi Jewish (AJ) patients (95 patients) and 7.1% in non-AJ patients (56 patients). In AJ patients with a strong, weak, or absent family history of BRCA-associated cancers, the mutation prevalence was 16.7%, 15.8%, and 7.4%, respectively. The mean age at the time of diagnosis in all mutation carriers was 58.5 years (range, 45-75 years) compared with 64 years (range, 27-87 years) in those not carrying a mutation (P = .02). Although BRCA2 was the most common mutation identified, no patients with early-onset PAC (diagnosed at age ≤ 50 years) harbored a BRCA2 mutation and the mean age at diagnosis in BRCA2 carriers was equivalent to that of individuals who were not mutation carriers (P = .34). Mutation prevalence in patients with early-onset disease (21 patients) was 28.6%, including BRCA1 (2 mutations), p16 (2 mutations), MSH2 (1 mutation), and MLH1 (1 mutation). CONCLUSIONS: Mutations in BRCA2 account for > 50% of patients with PAC with an identified susceptibility syndrome. AJ patients were found to have high BRCA1/BRCA2 prevalence regardless of personal/family history, suggesting that ancestry alone indicates a need for genetic evaluation. With the exception of BRCA2-associated PAC, an inherited predisposition for PAC is associated with an earlier age at PAC diagnosis, suggesting that this subset of patients may also represent a population warranting further evaluation.


Subject(s)
Adenocarcinoma/genetics , DNA Mismatch Repair/genetics , Genes, BRCA1 , Genes, BRCA2 , Genes, p16 , Germ-Line Mutation , Nuclear Proteins/genetics , Pancreatic Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Adaptor Proteins, Signal Transducing/genetics , Adenosine Triphosphatases/genetics , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Repair Enzymes/genetics , DNA-Binding Proteins/genetics , Fanconi Anemia Complementation Group N Protein , Female , Hereditary Breast and Ovarian Cancer Syndrome/genetics , Humans , Jews/genetics , Male , Middle Aged , Mismatch Repair Endonuclease PMS2 , MutL Protein Homolog 1 , MutS Homolog 2 Protein/genetics , Neoplastic Syndromes, Hereditary/genetics
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