Recent Publications by CFE Educators

BACKGROUND

The National Comprehensive Cancer Network guidelines recommend that patients with surgically resected head and neck cancers that have adverse pathologic features should receive adjuvant therapy in the form of radiotherapy (RT) or chemoradiation (CRT). To the authors' knowledge, the current study is the first analysis of temporal trends and use patterns of adjuvant therapy for these patients.

METHODS

Patients with head and neck cancer and adverse pathologic features were identified in the National Cancer Data Base (1998-2011). Data were analyzed using chi-square, Student t, and log-rank tests; multivariate logistic regression; and Cox multivariate regression.

RESULTS

A total of 73,088 patients were identified: 41.5% had received adjuvant RT, 33.5% had received adjuvant CRT, and 25.0% did not receive any adjuvant therapy. From 1998 to 2011, the increase in the use of adjuvant CRT was greatest for patients with oral cavity (6-fold) and laryngeal (5-fold) cancers. Multivariate analysis demonstrated that Medicare/Medicaid insurance (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.01-1.11), distance ≥34 miles from the cancer center (OR, 1.66; 95% CI, 1.59-1.74), and academic (OR, 1.26; 95% CI, 1.20-1.31) and high-volume (OR, 1.10; 95% CI, 1.05-1.15) centers were independently associated with patients not receiving adjuvant therapy. Receipt of adjuvant therapy was found to be independently associated with improved overall survival (hazard ratio, 0.84; 95% CI, 0.81-0.86).

CONCLUSIONS

Approximately 25% of patients are not receiving National Comprehensive Cancer Network guideline-directed adjuvant therapy. Patient-level and hospital-level factors are associated with variations in the receipt of adjuvant therapy. Further evaluation of these differences in practice patterns is needed to standardize practice and potentially improve the quality of care. Cancer 2014;120:3353-3360. © 2014 American Cancer Society.

BACKGROUND

Childhood obesity and overweight affect approximately 30% of US children. Many of these children have obesity-related comorbidities, such as hypertension, dyslipidemia, fatty liver disease, diabetes, polycystic ovary syndrome (PCOS), sleep apnea, psychosocial problems, and others. These children need routine screening and, in many cases, treatment for these conditions. However, because primary care pediatric providers (PCPs) often are underequipped to deal with these comorbidities, they frequently refer these patients to subspecialists. However, as a result of the US pediatric subspecialist shortage and considering that 12.5 million children are obese, access to care by subspecialists is limited. The aim of this article is to provide accessible, user-friendly clinical consensus statements to facilitate the screening, interpretation of results, and early treatment for some of the most common childhood obesity comorbidities.

METHODS

Members of the Children's Hospital Association (formerly NACHRI) FOCUS on a Fitter Future II (FFFII), a collaboration of 25 US pediatric obesity centers, used a combination of the best available evidence and collective clinical experience to develop consensus statements for pediatric obesity-related comorbidities. FFFII also surveyed the participating pediatric obesity centers regarding their current practices.

RESULTS

The work group developed consensus statements for use in the evaluation and treatment of lipids, liver enzymes, and blood pressure abnormalities and PCOS in the child with overweight and obesity. The results of the FFFII survey illustrated the variability in the approach for initial evaluation and treatment as well as pattern of referrals to subspecialists among programs.

CONCLUSIONS

The consensus statements presented in this article can be a useful tool for PCPs in the management and overall care of children with overweight and obesity.

Serum alpha-fetoprotein (AFP) has been increasingly recognized as a marker for a poor prognosis after liver transplantation (LT) for hepatocellular carcinoma (HCC). Many published reports, however, have included a large proportion of patients with HCC beyond the Milan criteria, and the effects of incorporating AFP as an exclusion criterion for LT remain unclear. We studied 211 consecutive patients undergoing LT for HCC within the Milan criteria according to imaging under the Model for End-Stage Liver Disease organ allocation system between June 2002 and January 2009. The majority (93.4%) had locoregional therapy before LT. The median follow-up was 4.5 years (minimum = 2 years). The Kaplan-Meier 1- and 5-year patient survival rates were 94.3% and 83.4%, respectively. In a univariate analysis, significant predictors of HCC recurrence included vascular invasion [hazard ratio (HR) = 10, 95% confidence interval (CI) = 3.9-26, P 0.001], a pathological tumor stage beyond the University of California San Francisco criteria (HR = 4.1, 95% CI = 1.36-12.6, P = 0.01), an AFP level > 1000 ng/mL (HR = 4.5, 95% CI = 1.3-15.3, P = 0.02), and an AFP level > 500 ng/mL (HR = 3.1, 95% CI = 1.04-9.4, P = 0.04). In a multivariate analysis, vascular invasion was the only significant predictor of tumor recurrence (HR = 5.6, 95% CI = 1.9-19, P = 0.02). An AFP level > 1000 ng/mL was the strongest pretransplant variable predicting vascular invasion (odds ratio = 6.8, 95% CI = 1.6-19.1, P = 0.006). The 1- and 5-year rates of survival without recurrence were 90% and 52.7%, respectively, for patients with an AFP level > 1000 ng/mL and 95% and 80.3%, respectively, for patients with an AFP level ≤ 1000 ng/mL (P = 0.026). Applying an AFP level > 1000 ng/mL as a cutoff would have resulted in the exclusion of 4.7% of the patients fr m LT and a 20% reduction in HCC recurrence. In conclusion, an AFP level > 1000 ng/mL may be a surrogate for vascular invasion and may be used to predict posttransplant HCC recurrence. Incorporating an AFP level > 1000 ng/mL as an exclusion criterion for LT within the Milan criteria may further improve posttransplant outcomes.

BACKGROUND

Studies have documented the short-term vascular benefits of combination lipid therapy.

OBJECTIVE

Our objective was to evaluate the long-term effects of combination lipid therapy on carotid intima-media thickness (CIMT) in patients with coronary artery disease.

METHODS

We performed a case-control study in patients who had finished the Familial Atherosclerosis Treatment Study (FATS) and returned to usual care with statin therapy alone or had elected to participate in the 20-year FATS-Observational Study (FATS-OS) and received combination therapy with lovastatin (40 mg/day), niacin (2-3 g/day), and colestipol (20 gm/day) for 11 years, then continued with simvastatin (10-80 mg/day) or lovastatin (40-80 mg/day) plus niacin (2-4 g/day). After 17.8 ± 0.8 years with combination therapy and 19.0 ± 0.8 years with usual care, cholesterol levels and CIMT were collected in 43 FATS-OS patients and 26 usual care patients.

RESULTS

Combination therapy group had a greater decrease in total cholesterol (-42 ± 14% vs -31 ± 17%, P = .008) and low-density lipoprotein cholesterol (LDL-C) (-57 ± 13% vs -38 ± 25%, P  .001) and greater increase in high-density lipoprotein cholesterol (HDL-C) (38 ± 43% vs 15 ± 23%, P = .02) as compared with usual care. CIMT (0.902 ± 0.164 vs 1.056 ± 0.169 mm, P  .001) on intensive therapy was significantly less compared with usual care. Multivariate regression analysis (coefficient, 95% CI) showed that combination therapy (-0.13; -0.21 to -0.04, P = .003) and on-therapy LDL-C (0.15; 0.02 to 0.28, P = .03) were significant independent predictors of CIMT.

CONCLUSIONS

Prolonged combination lipid therapy is associated with greater improvements in LDL-C and HDL-C levels and less atherosclerotic burden as compared with statin therapy alone.

The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface-expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface-directed antibody-mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface-directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined.

PURPOSE

Although long-term outcomes after initial placement of artificial urinary sphincters are established, limited data exist comparing sphincter survival in patients with compromised urethras (prior radiation, artificial urinary sphincter placement or urethroplasty). We evaluated artificial urinary sphincter failure in patients with compromised and noncompromised urethras.

MATERIALS AND METHODS

We performed a retrospective analysis of 86 sphincters placed at a single institution between December 1997 and September 2012. We assessed patient demographic, comorbid disease and surgical characteristics. All nonfunctioning, eroded or infected devices were considered failures.

RESULTS

Of the 86 patients reviewed 67 (78%) had compromised urethras and had higher failure rates than the noncompromised group (34% vs 21%, p=0.02). Compared to the noncompromised group, cases of prior radiation therapy (HR 4.78; 95% CI 1.27, 18.04), urethroplasty (HR 8.61; 95% CI 1.27, 58.51) and previous artificial urinary sphincter placement (HR 8.14; 95% CI 1.71, 38.82) had a significantly increased risk of failure. The risk of artificial urinary sphincter failure increased with more prior procedures. An increased risk of failure was observed after 3.5 cm cuff placement (HR 8.62; 95% CI 2.82, 26.36) but not transcorporal placement (HR 1.21; 95% CI 0.49, 2.99).

CONCLUSIONS

Artificial urinary sphincter placement in patients with compromised urethras from prior artificial urinary sphincter placement, radiation or urethroplasty had a statistically significant higher risk of failure than placement in patients with noncompromised urethras. Urethral mobilization and transection performed during posterior urethroplasty surgeries likely compromise urethral blood supply, predisposing patients to failure. Patients with severely compromised urethras from multiple prior procedures may have improved outcomes with transcorporal cuff placement rather than a 3.5 cm cuff.

OBJECTIVES

The management of complex colorectal polyps varies in practice. Accurate descriptions of the endoscopic appearance by using a standardized classification system (Paris classification) and size for complex colon polyps may guide subsequent providers regarding curative endoscopic resection vs. need for surgery. The accuracy of this assessment is not well defined. Furthermore, the factors associated with decisions for endoscopic vs. surgical management are unclear. To characterize the accuracy of physician assessment of polyp morphology, size, and suspicion for malignancy among physician subspecialists performing colonoscopy and colon surgery. In addition, we aimed to assess the influence of these polyp characteristics as well as physician type and patient demographics on recommendations for endoscopic vs. surgical resection of complex colorectal polyps.

METHODS

An online video-based survey was sent to gastroenterologists (GIs) and gastrointestinal surgeons affiliated with six tertiary academic centers. The survey consisted of high-definition video clips (30-60 s) of six complex colorectal polyps (one malignant) and clinical histories. Respondents were blinded to histology. Respondents were queried regarding polyp characteristics, suspicion for malignancy, and recommendations for resection.

RESULTS

The survey response rate was 154/317 (49%). Seventy-eight percent of respondents were attending physicians (91 GIs and 29 surgeons) and 22% were GI trainees. Sixteen percent of respondents self-identified as specialists in complex polypectomy. Accurate estimation of polyp size was poor (28.4%) with moderate interobserver agreement (k=0.52). Accuracy for Paris classification was 47.5%, also with moderate interobserver agreement (k=0.48). Specialists in complex polypectomy were most accurate, whereas surgeons were the least accurate in assigning Paris classification (66.0 vs. 28.7%, P0.0001). Specialists in complex polypectomy were most likely to correctly identify the malignant lesion compared with other physicians (87.5 vs. 56.2%, P=0.008). Surgical removal of colon adenomas was recommended least frequently by specialists in complex polypectomy (3.1%) compared with nonspecialists in complex polypectomy (13.3%); surgeons were most likely to recommend surgical resection (17.2%, P=0.009). There were no differences in recommendations for endoscopic vs. surgical resection observed on the basis of years in practice, polyp morphology (polypoid vs. nonpolypoid), polyp location (right vs. left colon), or patient ASA class.

CONCLUSIONS

In this large survey of GIs and surgeons, physician specialty was strongly associated with accurate polyp characterization and a recommendation for endoscopic resection of complex polyps. Surgeons were most likely to recommend surgical resection of complex nonmalignant colorectal polyps compared with specialists in complex polypectomy who were the least likely. Therefore, collaboration with specialists in complex polypectomy may be helpful in determining the appropriate management of complex colon polyps. Further teaching is needed among all specialists to improve accurate communication and ensure optimal management of these lesions.

The transmission of pruritoceptive (itch) messages involves specific neural circuits within the spinal cord that are distinct from those that transmit pain messages. These itch-specific circuits are tonically regulated by inhibitory interneurons in the dorsal horn. Consistent with these findings, it has previously been reported that loss of GABAergic interneurons in mice harboring a deletion of the transcription factor Bhlhb5 generates a severe, nonremitting condition of chronic itch. Here, we tested the hypothesis that the neuropathic itch in BHLHB5-deficient animals can be treated by restoring inhibitory controls through spinal cord transplantation and integration of precursors of cortical inhibitory interneurons derived from the embryonic medial ganglionic eminence. We specifically targeted the transplants to segments of the spinal cord innervated by areas of the body that were most severely affected. BHLHB5-deficient mice that received transplants demonstrated a substantial reduction of excessive scratching and dramatic resolution of skin lesions. In contrast, the scratching persisted and skin lesions worsened over time in sham-treated mice. Together, these results indicate that cell-mediated restoration of inhibitory controls has potential as a powerful, cell-based therapy for neuropathic itch that not only ameliorates symptoms of chronic itch, but also may modify disease.