CT Fluoroscopic-Guided Coil Localization of Lung Nodules prior to Video-Assisted Thoracoscopic Surgical Resection Reduces Complications Compared to Hook Wire Localization.

PURPOSE: To compare the safety and efficacy of hook wire versus microcoil localization of pulmonary nodules prior to video-assisted thoracoscopic resection (VATS). MATERIALS AND METHODS: A retrospective comparative review was conducted of 46 patients (26 hook wire and 20 microcoil) who underwent computed tomography fluoroscopic-guided nodule localizations prior to VATS in a single center between January 2012 and August 2016. Nodule characteristics, procedural details, clinical outcomes, and pathologic findings were collected. Baseline characteristics and lung nodule distribution were not significantly different between the 2 groups. Nodule sizes ranged from 2 mm to 28 mm and were similar between groups. Twenty-nine patients (63%) were male, with mean (standard deviation) age of 61 (11) years. Adverse events were classified using standard criteria. Patients were followed for up to 90 days, and the clinical outcomes were compared. RESULTS: Successful resection of nodules was achieved in all patients. Twelve cases of displacement of the hook wire were observed compared to only 1 in the coil group (P < .01). The total complication rate was lower in the coil group (25% vs 54%, P = .04). Two patients required transition to thoracotomy in the hook wire group, compared to none in the coil group. Median blood loss was similar in both groups (median loss, 20-22 mL). One patient had positive margins in the hook wire group. There was a nonsignificant trend toward longer hospital stay and higher major complication rates after hook wire localization (P = .4). CONCLUSIONS: Pulmonary nodule localization with coils prior to VATS resection demonstrated fewer displacements and fewer perioperative complications compared to hook wires.

Melanoma expression of matrix metalloproteinase-23 is associated with blunted tumor immunity and poor responses to immunotherapy.

BACKGROUND: Matrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca(2+) signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma. METHODS: We characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3(+) regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression. RESULTS: Our data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P = 0.05), in particular brisk TILs (P = 0.04), and a trend towards an increased proportion of immunosuppressive Foxp3(+) regulatory T cells (P = 0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P = 0.037) but not in those treated with vaccines (P = 0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P = 0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P = 0.27). CONCLUSIONS: Our data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.

Melanoma risk loci as determinants of melanoma recurrence and survival.

BACKGROUND: Steadily high melanoma mortality rates urge for the availability of novel biomarkers with a more personalized ability to predict melanoma clinical outcomes. Germline risk variants are promising candidates for this purpose; however, their prognostic potential in melanoma has never been systematically tested. METHODS: We examined the effect of 108 melanoma susceptibility single nucleotide polymorphisms (SNPs), associated in recent GWAS with melanoma and melanoma-related phenotypes, on recurrence-free survival (RFS) and overall survival (OS), in 891 prospectively accrued melanoma patients. Cox proportional hazards models (Cox PH) were used to test the associations between 108 melanoma risk SNPs and RFS and OS adjusted by age at diagnosis, gender, tumor stage, histological subtype and other primary tumor characteristics. RESULTS: We identified significant associations for rs7538876 (RCC2) with RFS (HR=1.48, 95% CI=1.20-1.83, p=0.0005) and rs9960018 (DLGAP1) with both RFS and OS (HR=1.43, 95% CI=1.07-1.91, p=0.01, HR=1.52, 95% CI=1.09-2.12, p=0.01, respectively) using multivariable Cox PH models. In addition, we developed a logistic regression model that incorporates rs7538876, rs9960018, primary tumor histological type and stage at diagnosis that has an improved discriminatory ability to classify 3-year recurrence (AUC=82%) compared to histological type and stage alone (AUC=78%). CONCLUSIONS: We identified associations between melanoma risk variants and melanoma outcomes. The significant associations observed for rs7538876 and rs9960018 suggest a biological implication of these loci in melanoma progression. The observed predictive patterns of associated variants with clinical end-points suggest for the first time the potential for utilization of genetic risk markers in melanoma prognostication.

Evaluation of postinjury hepatocyte function by central amino acid clearance.

It has been demonstrated by other investigators that central plasma clearance of amino acids accurately predicts hepatocyte function in patients with liver disease and correlates with clinical outcome. This methodology has not heretofore been studied in the trauma patient. It is our hypothesis that central amino acid clearance in trauma patients is more reflective of hepatocyte function than traditional liver function tests. We examined the plasma amino acid clearance rates using L-[1-13C]phenylalanine. Clearance rates were compared to standard liver function tests (LFTs) and the sensitivity and predictability of the technique were determined. The study was conducted on uninjured control subjects and in seriously injured patients, both with and without significant liver injuries. Compared to baseline values in the control group, initial phenylalanine breath scores were reduced in the injured, but exceeded control levels at 7 days postinjury. These changes were statistically significant. There was no difference between those with and without liver trauma. LFTs showed inconsistent and conflicting results. Thus, central amino acid clearance measured by L-[1-13C]phenylalanine oxidation is depressed immediately following injury but reaches supranormal levels at 7 days postinjury. Compared to LFTs, amino acid clearance suggests initial hepatocyte suppression followed by hyperactivity and is a more accurate determinant of hepatocyte function.

Duplex Ultrasound Versus Clinical Surveillance in the Prediction of TIPS Malfunction Placed for Refractory Ascites: Is Ultrasound Surveillance Useful?

PURPOSE: Since the advent of expanded polytetrafluoroethylene-covered stents and the improved patency they confer for transjugular intrahepatic portosystemic shunt (TIPS), the need to perform ultrasound surveillance has been debated. Prior reports have failed to separately evaluate patients who had TIPS placed for refractory ascites and variceal bleeding. The difference in morbidity from TIPS malfunction between these cohorts argues for distinction between the two. This retrospective review aims to determine whether Duplex ultrasound or return of symptoms more accurately predicts TIPS dysfunction. MATERIALS AND METHODS: Seventy-eight consecutive venograms in forty patients were retrospectively reviewed. TIPS venograms were used as the gold standard for TIPS dysfunction and considered abnormal if a pressure gradient >12 mmHg was discovered. Patients' charts were reviewed to assess for a return/worsening of ascites. Lastly, the two ultrasounds prior to TIPS revision were evaluated. RESULTS: The sensitivities of symptom relapse and ultrasound were 83 and 80.0%, respectively, while the specificities were 38.7 and 4.0%, respectively. The sensitivities were not found to be statistically different (p > 0.05); however, symptom relapse was found to be statistically more specific (p < 0.05). CONCLUSION: Symptom relapse is as sensitive and perhaps more specific than ultrasound in patients who had TIPS placed for refractory ascites.

Enhanced immunohistochemical detection of neural infiltration in primary melanoma: is there a clinical value?

Neural infiltration in primary melanoma is a histopathologic feature that has been associated with desmoplastic histopathologic subtype and local recurrence in the literature. We tested the hypothesis that improved detection and characterization of neural infiltration into peritumoral or intratumoral location and perineural or intraneural involvement could have a prognostic relevance. We studied 128 primary melanoma cases prospectively accrued and followed at New York University using immunohistochemical detection with antihuman neurofilament protein and routine histology with hematoxylin and eosin. Neural infiltration, defined as the presence of tumor cells involving or immediately surrounding nerve foci, was identified and characterized using both detection methods. Neural infiltration rate of detection was enhanced by immunohistochemistry for neurofilament in matched-pair design (47% by immunohistochemistry versus 25% by routine histology). Immunohistochemical detection of neural infiltration was significantly associated with ulceration (P = .021), desmoplastic and acral lentiginous histologic subtype (P = .008), and head/neck/hands/feet tumor location (P = .037). Routinely detected neural infiltration was significantly associated with local recurrence (P = .010). Immunohistochemistry detected more intratumoral neural infiltration cases compared with routine histology (30% versus 3%, respectively). Peritumoral and intratumoral nerve location had no impact on clinical outcomes. Using a multivariate model controlling for stage, neither routinely detected neural infiltration nor enhanced immunohistochemical characterization of neural infiltration was significantly associated with disease-free or overall survival. Our data demonstrate that routinely detected neural infiltration is associated with local recurrence in all histologic subtypes but that improved detection and characterization of neural infiltration with immunohistochemistry in primary melanoma does not add to prognostic relevance.

Mitotic rate in melanoma: prognostic value of immunostaining and computer-assisted image analysis.

The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm can change staging from T1a to T1b. Still, accurate mitotic rate calculation (mitoses/mm) on hematoxylin and eosin (H&E)-stained sections can be challenging. Antimonoclonal mitotic protein-2 (MPM-2) and antiphosphohistone-H3 (PHH3) are 2 antibodies reported to be more mitosis-specific than other markers of proliferation such as Ki-67. We used light microscopy and computer-assisted image analysis software to quantify MPM-2 and PHH3 staining in melanoma. We then compared mitotic rates by each method with conventional H&E-based mitotic rate for correlation with clinical outcomes. Our study included primary tissues from 190 nonconsecutive cutaneous melanoma patients who were prospectively enrolled at New York University Langone Medical Center with information on age, gender, and primary tumor characteristics. The mitotic rate was quantified manually by light microscopy of corresponding H&E-stained, MPM-2-stained, and PHH3-stained sections. Computer-assisted image analysis was then used to quantify immunolabeled mitoses on the previously examined PHH3 and MPM-2 slides. We then analyzed the association between mitotic rate and both progression-free and melanoma-specific survival. Univariate analysis of PHH3 found significant correlation between increased PHH3 mitotic rate and decreased progression-free survival (P=0.04). Computer-assisted image analysis enhanced the correlation of PHH3 mitotic rate with progression-free survival (P=0.02). Regardless of the detection method, neither MPM-2 nor PHH3 offered significant advantage over conventional H&E determination of mitotic rate.

Self-reported cardiac risks and interest in risk modification among volunteer firefighters: a survey-based study.

CONTEXT: Coronary heart disease causes approximately 45% of firefighter deaths annually. Although firefighters have clinically significant cardiac risks, a paucity of research and data exists. OBJECTIVE: To evaluate firefighters' cardiac risk factors as well as their motivation to resolve these risk factors. METHODS: During a 3-month period, volunteer firefighters representing the 79 fire departments serving Nassau and Suffolk counties in Long Island, NY, were asked to complete a nonvalidated, 19-item questionnaire regarding their health habits, medical history, and demographics. RESULTS: A total of 730 surveys were returned among a potential study population of 20,590 volunteer firefighters. More than three-quarters of respondents met the criteria for being overweight or obese, and nearly 40% reported having high blood pressure, high cholesterol, or both. Most respondents expressed at least some interest in attending a fire department-sponsored health lecture and participating in a fitness program. CONCLUSION: Firefighters expressed desire to learn more about risk factor modifications and have fire departments take a more active role in helping firefighters improve their health. The effectiveness of resources and intervention programs should be assessed.