DNA index is a strong predictive marker in intrahepatic cholangiocarcinoma: the results of a five-year prospective study.

PURPOSE: Predictive markers for risk stratification among patients with intrahepatic cholangiocarcinoma (IHC) are still lacking. Therefore, recent studies have focused on identifying the biological aspects of tumors that can provide more information about the tumor aggressiveness. The aim of this study was to prospectively evaluate the prognostic potential of the DNA index in patients undergoing liver resection for IHC. METHODS: In a prospective long-term follow-up study, the DNA index of 65 IHC patients undergoing liver resection was assessed by DNA image cytometry, and this parameter, as well as standard histopathological parameters, correlated with the patient survival. RESULTS: The mean DNA index was 1.69 ± 0.66 (range, 0.9-4.3). The univariate survival analysis showed that the DNA index (p = 0.024) and tumor stage (p = 0.017) were associated with patient survival, whereas all other standard histopathological factors had no predictive value. The multivariate analysis identified the DNA index (p = 0.050) and tumor stage (p = 0.028) as independent prognostic parameters. CONCLUSIONS: The DNA index is an independent predictive marker for IHC after liver resection. It is superior to most standard histopathological parameters and can be assessed pre- and postoperatively. Therefore, the DNA index might represent a promising tool in the decision-making process for patients with IHC.

Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier.

BACKGROUND & AIMS: IgG4-related cholangitis is a chronic inflammatory biliary disease that involves different parts of the pancreatobiliary system, but little is known about its mechanisms of pathogenesis. A T-helper (Th) 2 cell cytokine profile predominates in liver tissues from these patients. We investigated whether Th2 cytokines disrupt the barrier function of biliary epithelial cells (BECs) in patients with IgG4-related cholangitis. METHODS: We assessed the Th2 cytokine profile in bile samples and brush cytology samples from 16 patients with IgG4-related cholangitis and respective controls, and evaluated transcription of tight junction (TJ)-associated proteins in primary BECs from these patients. The effect of Th2 cytokines on TJ-mediated BEC barrier function and wound closure was examined by immunoblot, transepithelial resistance, charge-selective Na(+)/Cl(-) permeability, and 4-kDa dextran flux analyses. RESULTS: Bile samples from patients with IgG4-related cholangitis had significant increases in levels of Th2 cytokines, interleukin (IL)-4, and IL-5. IL-13 was not detected in bile samples, but polymerase chain reaction analysis of whole-brush cytology samples from patients with IgG4-related cholangitis revealed increased levels of IL-13 mRNA, compared with controls. BECs isolated from the brush cytology samples revealed decreased levels of claudin-1 and increased levels of claudin-2 mRNAs. In vitro, IL-4 and IL-13 significantly reduced TJ-associated BEC barrier function by activating claudin-2-mediated paracellular pore pathways. Th2 cytokines also impaired wound closure in BEC monolayers. CONCLUSIONS: Th2 cytokines predominate in bile samples from patients with IgG4-related cholangitis and disrupt the TJ-mediated BEC barrier in vitro. Subsequent increases in biliary leaks might contribute to the pathogenesis of chronic biliary inflammation in these patients.

DNA index as a strong prognostic factor in patients with adenocarcinoma of the pancreatic head: results of a 5-year prospective study.

OBJECTIVES: To improve the devastating prognosis of pancreatic cancer; the identification of reliable predictive factors is crucial. The aim of the present study was to prospectively assess the prognostic value of DNA index determined by image cytometry as an predictive factor in pancreatic head cancer. METHODS: The DNA ploidy and the DNA index of 61 patients were evaluated by DNA image cytometry and were found to be correlated, as well as standard histopathologic parameters, with patient survival. RESULTS: Through the DNA image cytometry, 15 tumors (24.6%) were identified as diploid and 46 (75.6%) as nondiploid. The median DNA index in the entire cohort was 1.9 (range, 1.0-2.5). Tumor stage, lymph node status, lymph node index, lymphatic invasion, and DNA index were identified as prognostic factors in the univariate analysis, but only DNA index (hazard ratio, 3.137; 95% confidence interval, 1.149-8.566; P = 0.026) and lymph node status (hazard ratio, 0.377; 95% confidence interval, 0.186-0.765; P = 0.007) were identified as independent predictive factors in the multivariate analysis. CONCLUSIONS: The DNA index represents an independent predictive marker in patients with pancreatic head cancer and a potential tool in designing specific treatment strategies for patients with pancreatic cancer.

Prospective pilot evaluation of a new needle prototype for endoscopic ultrasonography-guided fine-needle aspiration: comparison of cytology and histology yield.

OBJECTIVES: Endoscopic ultrasonography (EUS) with the adjunct of EUS-guided fine needle aspiration has become an important diagnostic modality in gastroenterologic oncology. EUS-guided fine needle aspiration mainly relies on cytology; data are scarce that compare cytology and histology. While testing a 22-gauge prototype needle, we prospectively compared the yield for both. METHODS: Forty-two consecutive patients (27 male, 15 female; mean age 59.2 years, range: 17-90 years) were included. In each patient we aimed to make two needle passes, and if the material acquired appeared insufficient macroscopically (no in-room cytopathology was available), further passes were done. The material was sent for cytological and histological assessment. RESULTS: A median number of two passes (range: 2-3) were uneventfully performed for pancreatic lesions (n=30), mediastinal and other lymph nodes/masses (n=8) and various other lesions (n=4) and yielded adequate material for cytology, histology or at least one of the two investigations in 62, 67 and 74% of patients, respectively. No false positive results were found (specificity 100%). Sensitivities were 58.6 and 65.5%, respectively, for cytology and histology alone; combined assessment increased sensitivity to 79.3%. When adjusted values were calculated, based only on those cases with adequate material, sensitivity was 89.5% for cytology and 85.7% for histology, and increased to 100% with combined assessment. CONCLUSION: The new needle achieves sensitivities similar to those previously reported with no significant differences in sensitivity between cytology and histology. More effective tissue acquisition methods must be sought to improve overall results.