Serum matrix metalloproteinase-7, Syndecan-1, and CA 19-9 as a biomarker panel for diagnosis of pancreatic ductal adenocarcinoma.

AIMS AND BACKGROUND: Matrix metalloproteinase-7 (MMP-7) and Syndecan-1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts. METHODS: In this case-control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups. Serum MMP-7 and SDC1 were measured by ELISA. The diagnostic accuracy of their levels for diagnosing PDAC and pancreatic cysts was computed, and their association with survival outcomes was evaluated. RESULTS: MMP-7 median serum levels were significantly elevated in the PDAC (7.3 ng/mL) and cyst groups (3.7 ng/mL) compared with controls (2.9 ng/mL) (p < 0.001 and 0.02, respectively), and also between the PDAC and cyst groups (p < 0.001), while SDC1 median serum levels were significantly elevated in PDAC (43.3 ng/mL) compared with either cysts (30.1 ng/mL, p < 0.001) or controls (31.2 ng/mL, p < 0.001). The receiver operating characteristic curve analysis area under the curve in PDAC versus controls was 0.90 and 0.78 for MMP-7 and SDC1, respectively, while it was 1.0 for the combination of the two and CA 19-9 (p < 0.001). The combination of the three biomarkers had a perfect sensitivity (100%). CONCLUSIONS: Due to its high sensitivity, this biomarker panel has the potential to rule out PDAC in suspected cases.

Serum Syndecan-1: A Novel Biomarker for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled alongside healthy individuals in a derivation-validation cohort design. Serum SDC1 was measured by enzyme-linked immunoassay. The diagnostic accuracy of SDC1 levels for diagnosing PDAC was computed. A unified cohort enriched with additional early-stage patients with PDAC was used to evaluate the association of SDC1 with survival outcomes and patient characteristics. RESULTS: In the derivation cohort, serum SDC1 levels were significantly higher in patients with PDAC (n = 39) compared with healthy controls (n = 20) (40.1 ng/mL, interquartile range 29.8-95.3 vs 25.6 ng/mL, interquartile range 17.1-29.8, respectively; P < 0.001). The receiver operating characteristic analysis area under the curve was 0.847 (95% confidence interval 0.747-0.947, P < 0.001). These results were replicated in a separate age-matched validation cohort (n = 38 PDAC, n = 38 controls; area under the curve 0.844, 95% confidence interval 0.757-0.932, P < 0.001). In the combined-enriched PDAC cohort (n = 110), using a cutoff of 35 ng/mL, the median overall 5-year survival between patients below and above this cutoff was not significantly different, although a trend for better survival after 1 year was found in the lower level group (P = 0.06). There were 12 of the 110 patients with PDAC (11%) who had normal CA 19-9 in the presence of elevated SDC1. DISCUSSION: These findings suggest serum SDC1 as a promising novel biomarker for early blood-based diagnosis of pancreatic cancer.

Acute diverticulitis: a decade of prospective follow-up.

BACKGROUND: Acute diverticulitis (AD) is the most common complication of diverticular disease and affects 10% to 25% of patients. Data regarding the natural history of AD are lacking. GOALS: Our aim was to prospectively assess the occurrence of recurrent attacks, surgeries, and accompanying symptoms in patients who were hospitalized with AD. STUDY: All patients hospitalized with first episode of AD between January 2000 and November 2006 were enrolled. Patients were followed up both during hospitalization and after discharge. Data regarding operations and complications were collected. Special attention was paid to patients younger than 45 years of age and compared with older patients. RESULTS: A total of 261 patients were identified-of them 103 were men. Thirty patients (11.5%) were 45 years old or younger. The mean follow-up period was 88±22 months (range, 52 to 184 mo). Younger patients experienced significantly more complications during hospitalization (37% vs. 12.5%, P=0.001) and underwent more often a sigmoidectomy in the follow-up period (42.3% vs. 18.3%, P=0.01). Older patients tended to be more often asymptomatic after discharge (P=0.053). The average time from index hospitalization to the sigmoidectomy was 18.17±23.35 months (range, 1 to 120 mo). The odds ratio for sigmoidectomy after complicated AD is 16.2 (95% confidence interval, 13.4 to 19.6). Age did not affect the risk for surgery. CONCLUSIONS: Younger patients with AD experience more complications during hospitalization and undergo surgery after discharge more frequently. Complicated AD at index hospitalization is a risk factor for sigmoidectomy. Our data can help predict the outcome of patients suffering from AD and enable tailoring an individual treatment.

Role of colonoscopy in patients with persistent acute diverticulitis.

AIM: To identify patients with persistent acute diverticulitis who might benefit from an early colonoscopy during their first hospitalization. METHODS: All patients hospitalized between July 2000 and December 2006 for acute diverticulitis who underwent colonoscopy were included in the study. Patients were followed during hospitalization and after discharge. Patients were considered to have a persistent course of acute diverticulitis if symptoms continued after 1 wk of conventional treatment with IV antibiotics, or if symptoms recurred within 2 mo after discharge. Patients were considered to benefit from an early colonoscopy if the colonoscopy was therapeutic or if it changed a patient's outcome. RESULTS: Three hundred and six patients were hospitalized between July 2000 and December 2006 with the diagnosis of acute diverticulitis. Two hundred and twenty four of these were included in the study group. Twenty three patients (10.3%) fulfilled the criteria for a persistent course of acute diverticulitis. Of them, four patients (17.4%) clearly benefited from an early colonoscopy; these patients' clinical course is described. None of the patients with a regular non-persistent course demonstrated any benefit from colonoscopy. CONCLUSION: Early colonoscopy detected other significant pathology, which accounted for the clinical presentation in 17% of patients with persistent acute diverticulitis. Therefore, we believe an early colonoscopy should be considered in all patients with a persistent clinical course.

Diverticulitis in the young patient--is it different ?

AIM: To prospectively study the incidence and the natural history of acute diverticulitis in young patients. METHODS: A total of 207 patients hospitalized at our hospital between January 2000 to February 2005 with the diagnosis of acute diverticulitis were included. Their demographic characteristics, medical history, physical, radiographic and endoscopic findings as well as therapy were recorded. Patients were followed every 6 mo for the first year and later annually. RESULTS: The mean patients' age was 61 (range 27-92) years. Twenty-five patients (12%) were younger than 45 years. Acute diverticulitis was significantly more prevalent among male in the young age group as compared to the older age group (19/25, 76% vs 61/182, 33%, respectively, P = 0.0001). Complications occurred more often in the young age group; 32% vs 13%, (P = 0.002). During follow-up, 6 patients (28%) remained asymptomatic in the young age group as compared to 87 patients (55%) in the older age group (P = 0.024). As a result, sigmoidectomies were performed twice as often in the young age group (38% vs 13%, P = 0.002). CONCLUSION: Diverticulitis in young patients has a male predominance, a more aggressive course with a higher rate of complications and a higher recurrence rate. An earlier surgical approach might be considered in young patients with acute diverticulitis.

Somatostatin inhibits pro-inflammatory cytokine secretion from rat hepatic stellate cells.

BACKGROUND/AIMS: Activated hepatic stellate cells (HSCs) have been implicated in hepatic fibrosis. Somatostatin (SOM) has an immunomodulatory role. The aim of this study was to assess the secretion of pro-inflammatory cytokines by HSCs and to determine the effect of SOM on the secretion of these mediators. METHODS: Activated rat HSCs were evaluated for their secretion of IL-1beta, IL-8, and TNF-alpha using ELISA. RNA protection assay was used to determine cytokine mRNA levels. The expression of chemokine and cytokine mRNA and the secretion of these mediators were assessed following incubation with SOM or octreotide. RESULTS: HSCs spontaneously secreted IL-1beta, IL-8, and TNF-alpha. This secretion was augmented following stimulation by IL-1beta and TNF-alpha. SOM inhibited the spontaneous and TNF-alpha-induced secretion of IL-1beta, IL-8, and TNF-alpha and suppressed the expression of IL-1beta and TNF-alpha mRNA. Octreotide suppressed the secretion of IL-1beta and IL-8. CONCLUSIONS: These observations indicate that SOM exerts an inhibitory immunomodulatory effect on HSCs.

Allicin inhibits spontaneous and TNF-alpha induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells.

BACKGROUND & AIMS: Allicin, the active substance of fresh crushed garlic has different biological activities and was implicated as an anti-inflammatory agent. Epithelial cells have an important role in intestinal inflammation. The aim of this study was to assess the immunomodulatory effect of allicin on intestinal epithelial cells. METHODS: The spontaneous and TNF-alpha-stimulated secretion of IL-1beta, IL-8, IP-10 and MIG from HT-29 and Caco-2 cells was tested with, or without pretreatment with allicin. Cytokine secretion was assessed using ELISA and expression of mRNA was determined by an RNA protection assay. RESULTS: Allicin markedly inhibited the spontaneous and TNF-alpha -induced secretion of IL-1beta, IL-8, IP-10 and MIG from the two different cell lines in a dose-dependent manner and suppressed the expression of IL-8 and IL-1beta mRNA levels. In addition, allicin suppressed the degradation of IkappaB. No effect on cell viability was noted. CONCLUSIONS: These observations indicate that allicin exerts an inhibitory immunomodulatory effect on intestinal epithelial cells and suggest that allicin may have the potential to attenuate intestinal inflammation.