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.

Patient-Reported Quality of Recovery after Sedation for Endoscopy in the Elderly.

INTRODUCTION: Although sedation is critical in minimizing discomforts in patients, conflicting data regarding the safety of sedation among the elderly population exist. This prospective study aimed to compare the quality of recovery (QoR) from gastrointestinal endoscopy performed under sedation between elderly and younger patients. METHODS: We included 177 patients aged 40-64 (group 1, n = 66), 65-79 (group 2, n = 76), and ≥80 (group 3, n = 35) years. QoR was assessed 1 day after the procedure using the quality of recovery 15 (QoR-15) questionnaire, which is a 15-item questionnaire with scores ranging from 0 to 150. Patient demographic, procedural, and sedation data were collected, and neurocognitive function was assessed before and a day after sedation. RESULTS: Groups 1 and 3 differed according to the Mini-Cog test and 3-word memory test performed before the procedure (p < 0.001). QoR-15 scores between groups were not different (139 ± 19 group 1, 141 ± 17 group 2, and 147 ± 26 group 3; p > 0.05). Patients in groups 3 and 2 were administered lower doses of propofol and midazolam than those in group 1. The incidence of oxygen desaturation (SaO2 <90% for >30 s) was lower in groups 1 and 2 than in group 3 (p = 0.01). CONCLUSIONS: As indicated by the QoR-15 questionnaire, the QoR from sedation was not significantly different between the study groups.

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.

Stenting in malignant colonic obstruction--is it a real therapeutic option?

BACKGROUND: Malignant colonic obstruction is commonly treated surgically. Colonic stents are a therapeutic option for palliation or used as a bridge to surgery or chemotherapy. OBJECTIVE: The aim of the study was to evaluate the clinical success rate of stenting as a bridge to one-step surgery, chemotherapy, or as a palliative measure. DESIGN: This was a retrospective observational study. SETTINGS: The study was conducted at a university-affiliated tertiary referral center. PATIENTS AND INTERVENTIONS: From 2007 to 2014, 45 patients with malignant colonic obstruction were referred for stent insertion. MAIN OUTCOME MEASURES: Patients were grouped according to three pre-defined treatment goals: group 1: restorative one-step procedure without an ostomy, group 2: completion of scheduled chemotherapy before surgery, and group 3: palliation without surgical intervention. RESULTS: Group 1 included 11 patients. Three patients (27.3 %) met the treatment goal of one-step surgery. Eight patients (72.7 %) did not reach the primary goal due to stent insertion failure (four patients), stent-related complications (two patients), and failure to perform a one-step surgery after successful stent insertion (two patients). Group 2 included 12 patients. Chemotherapy was successfully completed prior to surgery in six patients (50 %). Six patients (50 %) did not achieve treatment goal due to stent insertion failure (two patients), stent migration (two patients), stent-related perforation (one patient), and mortality (one patient). Group 3 included 20 patients. Long-term palliation without surgical intervention was achieved in eight patients (40 %). Stent insertion failed in seven patients (35 %). Five patients (25 %) needed urgent surgery due to stent complications (three migrations and two perforations). LIMITATIONS: The study was limited by its retrospective nature and small sample size. CONCLUSIONS: This study demonstrates only a modest success rate of colonic stents in the treatment of malignant colonic obstruction. Although colonic stenting seems to be an effective method of relieving colonic obstruction, high failure rates limits its applicability.

Double balloon enteroscopy: a 2 year experience.

BACKGROUND: Double balloon enteroscopy is a new technique that enables deep intubation of the endoscope into the small bowel lumen. Through a channel in the endoscope, invasive procedures such as biopsy, polypectomy and hemostasis can be performed, avoiding the need for surgery. OBJECTIVES: To prospectively analyze our results of the first 124 DBEs performed since February 2007. METHODS: The study group comprised all patients who underwent DBE at the Sheba Medical Center between February 2007 and February 2009. Recorded were the patients' demographic data, comorbidities, indications for the examination, results of previous non-invasive small bowel imaging (computed tomography enterography, capsule endoscopy, etc), investigation time, and results of the procedure including findings, endoscopic interventions, complications and pathological report. RESULTS: A total of 124 procedures were performed in 109 patients. Of the 124 examinations, 57 (46%) were normal and 67 (54%) showed pathology. The main pathologies detected on DBE were polyps (14%), vascular lesions (17.6%) and inflammation (12%). Endoscopic biopsies and therapeutic interventions were required in 58 examinations (46%). A new diagnosis was established in 15% of patients, diagnosis was confirmed in 29% and excluded or corrected in 12%. One complication was observed: a post-polypectomy syndrome that was treated conservatively. CONCLUSIONS: DBE is a safe procedure and has a high diagnostic and therapeutic yield. Most of the examinations were performed under conscious sedation, and only a minority of patients required deeper sedation.

The utility of capsule endoscopy in the diagnosis of Crohn's disease based on patient's symptoms.

BACKGROUND AND GOALS: Video capsule endoscopy (VCE) enables visualization of the entire small bowel and can identify lesions that may go undetected by conventional endoscopy and radiography. In this study, we assessed whether patient's selection based on symptoms may increase the yield of VCE in the diagnosis of Crohn's disease (CD). STUDY: Findings of 125 consecutive patients referred for VCE in whom CD may be suspected, were analyzed. Indications for VCE included iron-deficiency anemia, abdominal pain, diarrhea, or a combination of symptoms. Capsule endoscopy (CE) results were defined positive if 4 or more obvious clear ulcers, erosions, or a region with clear exudate and mucosal hyperemia and edema were identified. RESULTS: One hundred twelve patients were included in the final analysis. Mean age of patients was 44+/-22 years and median follow-up 36+/-15 months. Findings on CE were considered compatible with a diagnosis of CD in 7 patients (6%). In general, CE yielded a diagnosis of CD in a very small portion of the patients (0% to 4%), except in patients undergoing the test for a combination of abdominal pain and diarrhea. In this group, findings suggestive of inflammatory bowel disease were encountered in one-third of the patients (P=0.002). CONCLUSIONS: The greatest yield of CE in diagnosing CD is achieved in young patients who present with symptoms of abdominal pain plus diarrhea.

Endoscopic ultrasound staging of rectal cancer: diagnostic value before and following chemoradiation.

BACKGROUND: Endoscopic ultrasound (EUS) has been shown to be a reliable tool for staging rectal cancer. Nevertheless, the accuracy of EUS after chemoradiation remains unclear; therefore the purpose of the present paper was to compare the accuracy of EUS staging for rectal cancer before and following chemoradiation. METHODS: Patients with rectal cancer undergoing EUS staging were stratified into two groups. Group I consisted of 66 patients who underwent surgery following EUS staging without preoperative chemoradiation. Group II consisted of 25 patients who had EUS evaluation following chemoradiation. The EUS staging was compared to surgical/pathological staging. RESULTS: The accuracy of the T staging for group I was 86% (57/66). Inaccurate staging was mainly associated with overstaging EUS T2 tumors. The accuracy of the N staging for group I was 71% (47/66). The accuracy of EUS for a composite T and N staging relevant to treatment decisions in group I was 91%. In group II, the accuracy of T and N staging was 72% (18/25) and 80% (20/25), respectively. Overstaging EUS T3 tumors accounted for most inaccurate staging. The EUS staging predicted post-chemoradiation T0N0 stage correctly in only 50% of cases. CONCLUSIONS: Preoperative staging of rectal cancer by EUS is a useful modality in determining the need for preoperative chemoradiation. The EUS T staging following chemoradiation appears to be less accurate. Detection of complete response may be insufficient for selecting patients for limited surgical intervention.

Second capsule endoscopy for patients with severe iron deficiency anemia.

BACKGROUND: Patients with iron deficiency anemia are subjected to multiple endoscopic and radiologic examinations of the GI tract. If negative, some of the examinations are repeated, occasionally with positive findings. The diagnostic yield of a second capsule endoscopy in such patients is unknown. The aim of the current study was to assess the diagnostic yield of a second capsule endoscopy in patients with significant iron deficiency anemia and a previous negative evaluation. METHODS: Twenty patients with iron deficiency anemia (Hb < 10 g/dL) were enrolled. All had at least one normal evaluation of the GI tract, including capsule endoscopy. A second capsule endoscopy examination was offered to all patients. RESULTS: The time between the first and the second capsule endoscopy ranged from 2 months to 1 year. Depending on the nature of an abnormality and its relevance to blood loss, the findings were classified as positive, suspicious, clinically irrelevant, or negative. In 7 patients, the second capsule endoscopy disclosed findings that were classified as either positive or suspicious findings, including arteriovenous malformations (2), flat polypoid lesion (1), edematous inflamed mucosa (1), erosions (1), and hemorrhagic gastritis (1). Lesions were located in the small intestine (5), the stomach (1), and the cecum (1). Based on the findings of the second capsule endoscopy, therapy was changed in two patients (10%). CONCLUSIONS: A second capsule endoscopy should be considered for patients with severe iron deficiency anemia and negative initial evaluation.