Design of an immunohistochemistry biomarker panel for diagnosis of pancreatic adenocarcinoma.

BACKGROUND: Challenges still exist in differentiating pancreatic adenocarcinoma from benign disease. The use of adjuvant testing of tissue biopsies has demonstrated potential diagnostic value. We designed a proof of concept study to first validate four individual immunohistochemistry biomarkers and then combine them into a panel to boost overall diagnostic sensitivity. METHODS: Malignant and benign pancreas from 27 pancreaticoduodenectomy specimens underwent immunohistochemistry staining with VHL, IMP3, S100A4, S100P. Using ROC curve analysis, threshold criteria for number of cells staining were chosen for each biomarker. Biomarkers were then evaluated as a panel for their ability to discriminate malignant from benign specimens. RESULTS: Diagnostic sensitivity of VHL, IMP3, S100A4, and S100P were 75.0%, 79.2%, 45.8%, and 0%. When VHL, IMP3, and S100A4 were grouped into a panel, they were able to distinguish cancer from normal tissue with a sensitivity of 100% and a specificity of 96%. CONCLUSIONS: The high diagnostic value of an IHC panel consisting of VHL, IMP3, and S100A4 on surgical specimens suggests the need for future prospective studies of these biomarkers on biopsy specimens.

Cost-Effectiveness of Sentinel Lymph Node Biopsy for Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has shown promise in identifying subclinical nodal metastasis in patients with high-risk cutaneous squamous cell carcinoma. However, low metastasis rates may indicate that performing such a procedure in all patients may be unnecessary and costly. MATERIALS AND METHODS: A decision model was developed to analyze costs and survival in patients with head and neck cutaneous squamous cell carcinoma based on their tumor and nodal metastasis staging and whether or not they received an SLNB. Incremental cost-effectiveness ratios were calculated based on the change in quality-adjusted life years (QALYs) and costs (US$) between the different options, with a threshold of $100,000 to determine the most cost-effective strategy. One-way, two-way, and probabilistic sensitivity analyses were performed to validate the results. RESULTS: Not performing an SLNB results in 12.26 QALYs and a cost of $3712.98. Performing an SLNB resulted in a 0.59 decrease in QALYs and an increase in cost of $1379.58 for an incremental cost-effectiveness ratio of -2338.27. This trend remained the same across all tumor stages and remained consistent within most sensitivity analyses. CONCLUSIONS: In patients with head and neck cutaneous squamous cell carcinoma, the most cost-effective strategy is to not perform SLNBs, regardless of the patient's stage. Low rates of nodal metastasis in addition to low disease-specific death rates were the significant factors in this outcome. Increasing the sensitivity of SLNB would not impact this recommendation unless the rate of nodal metastasis was significantly higher.

Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell carcinoma: A National Cancer Database study.

BACKGROUND: Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC). METHODS: Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy. RESULTS: There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases). CONCLUSION: Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications.

Predictors of Clinicopathologic Stage Discrepancy in Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study.

Objective To determine the frequency, associated factors, and prognosis of clinicopathologic stage discrepancy in oropharyngeal squamous cell carcinoma (OPSCC). Study Design Retrospective study using a national database. Setting National Cancer Database. Subjects and Methods Cases of OPSCC diagnosed between January 1, 2004, and December 31, 2013, with full clinical and pathologic staging information available were identified. Demographic, clinicopathologic, and treatment variables associated with overall stage discrepancy were identified by multivariate logistic regression analysis. Results In total, 7731 cases of OPSCC were identified. Overall stage discrepancy was present in 30.2% of cases (21.9% upstaging, 8.2% downstaging). A total of 13.1% of cases were T-upstaged, and 10.5% of cases were T-downstaged; 22.9% of cases were N-upstaged, and 8.6% of cases were N-downstaged. Upstaging by overall stage was associated with a high Charlson-Deyo score, high tumor grade, number of lymph nodes examined, and increasing tumor size. No factors were positively associated with downstaging. High tumor grade was negatively associated with downstaging. For stage II, III, and IVA tumors, upstaging was associated with poorer OS. Conclusion Clinicopathologic stage discrepancy is common in OPSCC and is likely attributable to insensitive clinical staging techniques as well as to intrinsic tumor biologic properties. Upstaging is associated with poorer prognosis, which is likely due to advancement of disease.

Improving cancer patient emergency room utilization: A New Jersey state assessment.

INTRODUCTION: Due to its increasing incidence and its major contribution to healthcare costs, cancer is a major public health problem in the United States. The impact across different services is not well documented and utilization of emergency departments (ED) by cancer patients is not well characterized. The aim of our study was to identify factors that can be addressed to improve the appropriate delivery of quality cancer care thereby reducing ED utilization, decreasing hospitalizations and reducing the related healthcare costs. METHODS: The New Jersey State Inpatient and Emergency Department Databases were used to identify the primary outcome variables; patient disposition and readmission rates. The independent variables were demographics, payer and clinical characteristics. Multivariable unconditional logistic regression models using clinical and demographic data were used to predict hospital admission or emergency department return. RESULTS: A total of 37,080 emergency department visits were cancer related with the most common diagnosis attributed to lung cancer (30.0%) and the most common presentation was pain. The disposition of patients who visit the ED due to cancer related issues is significantly affected by the factors of race (African American OR=0.6, p value=0.02 and Hispanic OR=0.5, p value=0.02, respectively), age aged 65 to 75years (SNF/ICF OR 2.35, p value=0.00 and Home Healthcare Service OR 5.15, p value=0.01, respectively), number of diagnoses (OR 1.26, p value=0.00), insurance payer (SNF/ICF OR 2.2, p value=0.02 and Home Healthcare Services OR 2.85, p value=0.07, respectively) and type of cancer (breast OR 0.54, p value=0.01, prostate OR 0.56, p value=0.01, uterine OR 0.37, p value=0.02, and other OR 0.62, p value=0.05, respectively). In addition, comorbidities increased the likelihood of death, being transferred to SNF/ICF, or utilization of home healthcare services (OR 1.6, p value=0.00, OR 1.18, p value=0.00, and OR 1.16, p value=0.04, respectively). Readmission is significantly affected by race (American Americans OR 0.41, standard error 0.08, p value=0.001 and Hispanics OR 0.29, standard error 0.11, p value=0.01, respectively), income (Quartile 2 OR 0.98, standard error 0.14, p value 0.01, Quartile 3 OR 1.07, standard error 0.13, p value 0.01, and Quartile 4 OR 0.88, standard error 0.12, p value 0.01, respectively), and type of cancer (prostate OR 0.25, standard error 0.09, p value=0.001). CONCLUSION: Web based symptom questionnaires, patient navigators, end of life nursing and clinical cancer pathways can identify, guide and prompt early initiation of treat before progression of symptoms in cancer patients most likely to visit the ED. Thus, improving cancer patient satisfaction, outcomes and reduce health care costs.

Role of PROPELLER diffusion-weighted imaging and apparent diffusion coefficient in the evaluation of pituitary adenomas.

OBJECTIVE: The relationship between tumor consistency and apparent diffusion coefficient (ADC) values is controversial. We evaluated the role of the ADC using an advanced diffusion-weighted imaging (DWI) technique. We employed periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) DWI acquired on a 3-T magnetic resonance imaging (MRI) scanner to assess the consistency of pituitary adenomas and examined the relationship between the ADC and the hormone secretion status of the tumors and their MIB-1 labeling index (MIB-1 LI). MATERIALS AND METHODS: The study protocol was approved by our institutional review board. We retrospectively studied 24 operated patients with pituitary adenomas who had undergone PROPELLER DWI on a 3-T MRI scanner. Conventional MRI findings were expressed as the ratio of the signal intensity (SI) in the lesions to the SI of the normal white matter and the degree of contrast enhancement. Minimum-, mean-, and maximum ADC (ADCmin, ADCmean, ADCmax) values were calculated. The consistency of the tumors was determined by neurosurgeons. All surgical specimens were submitted for histological study to calculate the MIB-1 LI and the percent collagen content. Preoperative MRI-, intraoperative-, and histological findings were analyzed by a statistician. RESULTS: Our study included 15 soft-, 5 fibrous-, and 4 hard tumors. Tumor consistency was strongly associated with the percent collagen content. However, neither the tumor consistency nor the percent collagen content was correlated with MRI findings or ADC values. The SI of growth hormone-producing adenomas on T2-WI was lower than of the other pituitary adenomas studied (p<0.01); no other significant difference was found in the ADC or on conventional MRI between pituitary adenomas with different secretory functions. The MIB-1 LI of pituitary adenomas was not correlated with their appearance on conventional MRI or their ADC values. CONCLUSION: Using the PROPELLER DWI technique we confirmed that the ADC was not correlated with the consistency of pituitary adenomas. We also demonstrate that the ADC was not associated with the hormone-secreting status or the MIB-1 LI of pituitary adenomas.

Role of PROPELLER diffusion weighted imaging and apparent diffusion coefficient in the diagnosis of sellar and parasellar lesions.

OBJECTIVE: To evaluate the role of the apparent diffusion coefficient (ADC) using periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) diffusion weighted imaging (DWI) in the differentiation between sellar and parasellar mass lesions. MATERIALS AND METHODS: The study protocol was approved by our institutional review board. We retrospectively studied 60 patients with sellar and parasellar lesions who had undergone PROPELLER DWI on a 3-T MR imager. Conventional MRI findings were expressed as the ratio of signal intensity (SI) in the lesions to the normal white matter and the degree of contrast enhancement. ADC values were calculated as the minimum (ADC-MIN), mean (ADC-MEAN), and maximum (ADC-MAX). All patients underwent surgery and all specimens were examined histologically. Logistic discriminant analysis was performed by using the SI ratios on T1- and T2-weighted images (T1-WI, T2-WI), the degree of enhancement, and absolute ADC values as independent variables. RESULTS: ADC-MIN of hemorrhagic pituitary adenomas was lower than of the other lesions with similar appearance on conventional MRI (non-hemorrhagic pituitary adenomas, craniopharyngiomas, Rathke's cleft cysts; accuracy 100%); the useful cut-off value was 0.700 x 10(-3)mm(2)/s. ADC-MAX of meningiomas was lower than of non-hemorrhagic pituitary adenomas (accuracy 90.3%; p<0.01). ADC-MIN of craniopharyngiomas was lower than of Rathke's cleft cysts (accuracy 100%; p<0.05). CONCLUSION: As PROPELLER DWI is less sensitive to susceptibility artifacts than single-shot echoplanar DWI, it is more useful in the examination of sellar and parasellar lesions. Calculation of the ADC values helps to differentiate between various sellar and parasellar lesions.