Tumor markers in pancreatic cystic fluids for diagnosis of malignant cysts.

BACKGROUND AND AIM: Early diagnosis of premalignant or malignant pancreatic cysts is essential to improve prognosis. Sampling of pancreatic cyst fluid by fine-needle aspiration during endoscopic ultrasonography (EUS) enables cytopathological examination combined with biochemical analysis. This study aimed to provide an aid based on biological markers for the preoperative management of patients with pancreatic cysts. METHODS: Pancreatic fluids obtained by EUS-guided fine-needle aspiration from 115 patients with cystic lesions were assayed for amylase, lipase, carcinoembryonic antigen (CEA), CA 19-9 and CA 72-4. In addition, chromogranin A (CgA) and neuron-specific enolase (NSE) were measured in 28 fluid samples. RESULTS: ROC curve analysis of the different markers for diagnosis of mucinous cysts showed that CEA had the highest area under the curve (0.93, 95% CI 0.87-0.97), with a sensitivity and specificity of 89% and 93%, respectively, at the cutoff value of 317 µg/L. The CgA and NSE concentrations in 5 NET cysts (median values of 210 [63-492] and 68.5 [9-496] µg/L, respectively) were higher than in 23 other cysts (median values of 8 [7-828] and 2.7 [0.5-35.8] µg/L, respectively) (p = 0.0015 and p = 0.0045, respectively). CONCLUSIONS: CEA is the best marker for identifying a cyst as mucinous. In case of low levels of CEA, our results suggest that CgA and NSE measurements may be helpful in the diagnosis of a neuroendocrine tumor and therefore deserve further investigation.

Automated two-site immunofluorescent assay for the measurement of serum chromogranin A.

OBJECTIVES: Chromogranin A (CgA) is the best-characterized biological marker common to neuroendocrine tumours and is therefore recommended for their diagnosis. The measurement of serum CgA is of great importance for reaching an early diagnosis and thus reducing the delay before treatment is instigated. The Kryptor CgA assay is the first fully automated assay available. The aim of this study was to evaluate its analytical performance. DESIGN AND METHODS: The imprecision and linearity of the Kryptor CgA assay were evaluated. This assay was compared with the Cis Bio CgA RIA assay in 78 serum samples. Its clinical utility was assessed in serum from 229 patients. RESULTS: The study performed on imprecision of Kryptor measurements showed intra- and inter-run CVs ≤ 5%. The study of linearity showed a satisfactory recovery rate for CgA concentrations up to 1200 µg/L. The Kryptor and RIA assays agreed well on the basis of the cut-off values provided by the two manufacturers. The Bland and Altman plot of the values obtained (range: 20-5560 µg/L) provided a mean difference of -10.1 µg/L (SD: 116). The clinical sensitivities of Kryptor CgA for diagnosis of pheochromocytoma and paraganglioma (n 20) and gastroenteropancreatic NETs (n 17) were respectively 100 and 94%. CONCLUSIONS: The Kryptor assay for CgA shows reliable analytical and clinical characteristics and allows a fast delivery of results.

Interleukin-10 promoter (-1082) polymorphism in association with repeated hospital-acquired infections in elderly patients.

BACKGROUND: Infections are frequent complications of hospitalization, particularly in the elderly. Pro- and anti-inflammatory cytokines are essential components of the host response to pathogens and polymorphisms in their genes may contribute to inter-individual variations of the inflammatory response. The aim of this study was to investigate whether cytokine polymorphisms, separately or in combination, could be determining factors in the development of repeated nosocomial infections in elderly hospitalized patients. METHODS: Tumor necrosis factor-α (-308) and (-238), interleukin-6 (-174) and (-6331), interleukin-10 (-1082) and (-592) polymorphisms were genotyped by PCR and hybridization with fluorescent-labeled probes in 245 hospitalized elderly patients (mean age 85.2 years; SD 6) and compared with those in 145 healthy adults. RESULTS: The distribution of genotypes did not differ between elderly patients and control subjects. The presence of the interleukin-10 A(592) or A(1082) allele was more frequent individually and after adjustment for multiple comparisons in patients who suffered from several infections (p = 0.012, odds ratio = 5.3; 95 % confidence interval = 1.2-23.1). CONCLUSION: Our data support a determinant role for interleukin-10 (-1082) polymorphism in the development of nosocomial infections.

TMPRSS2-ERG fusion transcripts in matched urine and needle rinse material after biopsy for the detection of prostate cancer.

BACKGROUND: Current methods for detecting TMPRSS2-ERG fusion transcript in the urine of patients with suspected prostate cancer lack diagnostic sensitivity. We combined urine and prostate biopsy rinse material (BRM) assays to improve the fusion gene detection rate. METHODS: Eighty patients with clinical and/or prostate-specific antigen suspicion of prostate cancer were prospectively included in the study. Urine samples were collected before and after prostate biopsy, and BRM was collected from the biopsy needle. We used reverse-transcription PCR (RT-PCR) for the detection of fusion transcripts. Microfocal cancer (MFC) on biopsy was defined by a single core involved with ≤3 mm of cancer with Gleason score 3 + 3. We statistically assessed the association between RT-PCR and biopsy results. RESULTS: Urine alone, BRM alone, and both samples were obtained in 4, 19, and 57 patients, respectively. Three patients were excluded because of insufficient material. In the remaining 77 patients, cancer was detected on biopsy in 42 (55%). The diagnostic sensitivity of the assay for cancer detection was 62% (95% CI 47%-78%), 69% (53%-85%), and 89% (73%-99%) with BRM alone, urine alone, and paired samples, respectively. The lowest values were obtained with the urine assay in patients with MFC or Gleason score >3 + 3 cancer. Assays of paired samples provided increased diagnostic sensitivity in all subgroups of patients. CONCLUSIONS: TMPRSS2-ERG fusion gene detection may be improved by performing assays in both urine and BRM. Insufficient cell numbers in urine samples and cell lysis during centrifugation may explain the low diagnostic sensitivity of the urine assay.

The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients.

Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (P<0.05). Ala-Gln was undetectable with enteral administration, whereas Ala-Gln remained stable at a plasma concentration of 268 micromol/l throughout parenteral infusion and rapidly decreased towards zero after infusion was stopped. The highest level of glutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

Ontogenic and adult whole body distribution of aminopeptidase N in rat investigated by in vitro autoradiography.

Aminopeptidase N (APN), which is widely distributed in mammalian tissues, is able to cleave numerous regulatory peptides. The selective inhibitor of APN, [(125)I] RB129, has been used to study the distribution of this exopeptidase during rat prenatal development and adult life by in vitro whole-body autoradiography. In the central nervous system, APN shows a weak labeling compared to the major part of the non-nervous tissues in the embryo and in the adult. APN is progressively expressed in kidney, intestine, heart, lung, sensory organs, eye, and thymus. In organs such as the liver, the cartilages and the bones, altered levels of APN expression are observed during the development, or in the embryo compared to the adult, suggesting a role of APN during the liver haematopoiesis and bone growth. At this time, all the physiological functions of APN are still incompletely known, however its developmental pattern of expression strongly suggests a function of modulation of this enzyme during the development, next in physiological and/or pathological situations in adult. In this way, APN could represent a new therapeutic target in pathological processes, such as tumoral proliferation and/or angiogenesis associated with cancer development, where an increase in the level of this enzyme has been observed.