The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms.

BACKGROUND: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. METHODS: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. RESULTS: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. CONCLUSIONS: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

Chronic Urticaria Biomarkers IL-6, ESR and CRP in Correlation with Disease Severity and Patient Quality of Life-A Pilot Study.

(1) Background: To assess the relationship between serum interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values and disease severity in patients with chronic spontaneous urticaria (CSU) and to examine which of these serum biomarkers better indicates disease severity. (2) Methods: Our pilot study included 20 patients with CSU who filled out questionnaires concerning disease severity and quality of life (the Urticaria Activity Score summed over 7 days [UAS7], the once-daily Urticaria Activity Score [UAS], the Urticaria Control Test [UCT], and the Dermatology Life Quality Index [DLQI]). Blood samples were taken to measure IL-6, ESR and CRP. (3) Results: ESR significantly correlated with the UAS7 (linear and moderate correlation; r = 0.496; p = 0.026), while CRP did not correlate with disease severity. IL-6 correlated with the once-daily UAS (r = 0.472; p = 0.036) and DLQI (r = 0.504; p = 0.023) (linear and moderate correlation) but not the UAS7 or UCT. (4) Conclusions: IL-6 was a better indicator of the once-daily UAS and DLQI, while ESR was a better indicator of the UAS7 (there was no correlation between IL-6, CRP and ESR parameters). Although our results are promising, this study should be conducted with a larger number of CSU patients.

A score derived from routine biochemical parameters increases the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms.

BACKGROUND: Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs. METHODS: This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs. RESULTS: CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713-0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430). CONCLUSIONS: CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.

Prognostic significance of DNA cytometry in combination with AgNOR investigation.

CONCLUSION: While most results concerning DNA and nucleolar organizer region (AgNOR) parameters fit with previous studies, the percentage of aneuploidy looks like a promising prognostic parameter. The observed intratumoral heterogeneity could represent a possible source of conflicting and inconsistent results. OBJECTIVES: The aims of our study were to determine the prognostic relevance of different DNA and AgNOR parameters in laryngeal squamous cell carcinoma (SCC) and compare these findings with established prognostic factors including tumor stage and grade, as well as the detection of possible intratumoral heterogeneity. MATERIALS AND METHODS: Sections from 62 laryngeal SCCs were analyzed for DNA content, DNA index, S-phase, percentage of aneuploidy, and AgNOR. Of 62 samples, 31 morphologically similar tumor samples were analyzed for the same parameters in three different tumor areas defined as tumor center, invasive tumor margin, and transformation margin between tumor and normal-appearing mucosa. RESULTS: Our study showed that DNA and AgNOR parameters correlated with T stage, lymph node involvement, and histologic grade regardless of tumor areas. Significant correlation was found between mean number of AgNOR per nucleus and percentage of aneuploidy. Clinical stage and percentage of aneuploidy correlated with survival (p<0.02). Heterogeneity DNA study revealed aneuploidy in central portions of 90% of tumors, while in margins aneuploidy was demonstrated in about half of the patients.

Heterogeneity of DNA content in laryngeal squamous cell carcinoma in relation to histopathological variables.

CONCLUSION: Multivariate analysis showed age, lymph node status, proliferative index in transformation border, and DNA index in the center of laryngeal squamous cell carcinoma to be significant predictors for survival. By accessing distinctive areas of the tumor we were able to reduce the impact of intratumoral heterogeneity on prognostic factors. OBJECTIVES: Laryngeal carcinomas are characterized by considerable histological variation within the tumor. The possible effects of this morphological heterogeneity on the estimation of tumor DNA content were investigated. MATERIALS AND METHODS: We analyzed 92 cases of archived, paraffin-embedded laryngeal carcinoma. For each tumor, three different regions, defined microscopically (center of tumor, transformation border, invasive border), were analyzed. DNA content was measured by flow cytometry. Three parameters were evaluated: DNA ploidy, DNA index, and proliferative index. RESULTS: DNA ploidy, DNA index, and proliferative index were higher in the tumor center than in the respective borders. Intratumoral differences in DNA ploidy were observed in 56 tumors (60.8%); DNA index heterogeneity was observed in 57.6% cases. Proliferative index varied greatly in morphologically different parts of the same carcinoma. DNA ploidy and DNA index of the transformation border correlated with tumor size and lymph node status. Proliferative index of the tumor center and of transformation border correlated with lymph node status, tumor size, and histological grade.