Kanwar R. Gill

CXC-chemokine/CXCR2 biological axis promotes angiogenesis in vitro and in vivo in pancreatic cancer

Angiogenesis is essential for tumor growth and metastasis. Although ELR+‐CXC‐chemokines and their corresponding receptor, CXC‐receptor 2 (CXCR2), are known mediators of angiogenesis, little is known about their role in pancreatic cancer (PaCa). The aim of our study was to determine the role of ELR+‐CXC‐chemokine/CXCR2 biological axis in promoting PaCa angiogenesis. We prospectively collected secretin‐stimulated exocrine pancreatic secretions (SSEPS) from normal individuals (NP) and PaCa patients. We showed that summed concentrations of ELR+‐CXC‐chemokines in SSEPS from PaCa patients were significantly higher than in those from NP (p = 0.002). We measured ELR+‐CXC‐chemokine levels in supernatants from multiple PaCa cell lines and confirmed that BxPC‐3, Colo‐357 and Panc‐28 had significantly higher expression compared with an immortalized human pancreatic ductal epithelial (HPDE) cell line. After confirming lack of autocrine effects of ELR+‐CXC‐chemokines on PaCa cells (due to absence of CXCR2 expression), we investigated paracrine effects of these chemokines on human umbilical vein endothelial cells (HUVEC). Both recombinant ELR+‐CXC‐chemokines and co‐culturing with BxPC‐3 significantly enhanced proliferation, invasion, and tube formation of HUVEC (p < 0.05). These biological effects were significantly inhibited by treatment with a neutralizing antibody against CXCR2 (anti‐CXCR2 Ab) (p < 0.05). Finally, anti‐CXCR2 Ab significantly reduced tumor volume (p < 0.05), Ki‐67 proliferation index (p = 0.043) and Factor VIII+ microvessel density (p = 0.004) in an orthotopic nude mouse PaCa model. Our results show that ELR+‐CXC‐chemokines promote PaCa tumor‐associated angiogenesis through CXCR2, suggesting that CXCR2 is an anti‐angiogenic target in PaCa.

Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy

BACKGROUND Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. OBJECTIVE To assess the safety and efficacy of cryotherapy in esophageal carcinoma. DESIGN Multicenter, retrospective cohort study. SETTING Ten academic and community medical centers between 2006 and 2009. PATIENTS Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. INTERVENTIONS Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. MAIN OUTCOME MEASUREMENTS Complete eradication of luminal cancer and adverse events. RESULTS Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. LIMITATIONS Retrospective study design, short follow-up. CONCLUSIONS Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.

High-Definition Colonoscopy Detects Colorectal Polyps at a Higher Rate Than Standard White-Light Colonoscopy

BACKGROUND & AIMS Adenoma detection rates might be improved through use of high-definition colonoscopy, which can detect subtle mucosal changes. We investigated whether the use of high-definition white-light (HDWL) colonoscopy resulted in a higher rate of adenoma detection than standard-definition white-light (SDWL) colonoscopy in a clinical practice setting. METHODS This retrospective study included 2430 patients who underwent colonoscopies from September 2006 to December 2007; 1226 received SDWL colonoscopy and 1204 received HDWL colonoscopy. We analyzed data from consecutive screening, surveillance, and diagnostic colonoscopies, comparing adenoma and overall polyp detection between procedures. Potentially confounding variables were controlled using multivariable logistic regression analysis. RESULTS The adenoma detection rate was higher among patients who underwent HDWL compared with SDWL colonoscopies (28.8% vs 24.3%; P = .012), as was the polyp detection rate (42.2% vs 37.8%; P = .026). These findings remained after adjustments for potentially confounding variables (P = .018 and .022, respectively). CONCLUSIONS In a general clinical practice setting, HDWL colonoscopy resulted in a higher adenoma detection rate compared with SDWL colonoscopy. The use of SDWL colonoscopy could reduce the number of missed adenomas and the subsequent risk for colorectal cancer.

Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer.

Lung cancer remains the most common cause of cancer-related death in the United States. This study evaluated the costs of alternative diagnostic evaluations for patients with suspected non-small cell lung cancer (NSCLC). Researchers used a cost-minimization model to compare various diagnostic approaches in the evaluation of patients with NSCLC. It was less expensive to use an initial endoscopic ultrasound (EUS) with fine needle aspiration (FNA) to detect a mediastinal lymph node metastasis (

Safety and efficacy of cytology brushings versus standard fine-needle aspiration in evaluating cystic pancreatic lesions: a controlled study.

18,603 per patient), compared with combined EUS FNA and endobronchial ultrasound (EBUS) with FNA (

Endoscopic mucosal ablation for the treatment of gastric antral vascular ectasia with the HALO90 system: a pilot study

18,753). The results were sensitive to the prevalence of malignant mediastinal lymph nodes; EUS FNA remained least costly, if the probability of nodal metastases was <32.9%, as would occur in a patient without abnormal lymph nodes on computed tomography (CT). While EUS FNA combined with EBUS FNA was the most economical approach, if the rate of nodal metastases was higher, as would be the case in patients with abnormal lymph nodes on CT. Both of these strategies were less costly than bronchoscopy or mediastinoscopy. The pre-test probability of nodal metastases can determine the most cost-effective testing strategy for evaluation of a patient with NSCLC. Pre-procedure CT may be helpful in assessing probability of mediastinal nodal metastases.

Patient outcomes after total pancreatectomy: a single centre contemporary experience

BACKGROUND AND STUDY AIMS Cystic pancreatic lesions (CPLs) are increasingly detected by various imaging studies. Mucinous CPLs carry a risk of malignant transformation but this is often difficult to diagnose preoperatively. In a previous report of 10 suspected mucinous CPLs, the cellular yield of endoscopic ultrasonography (EUS)-guided cytology brushings was found to be superior to the yield from standard fine-needle aspiration (FNA). The aim of this prospective and blinded study was to compare the cytology yield of mucinous epithelium from brushing with FNA in suspected mucinous CPLs. PATIENTS AND METHODS In total, 37 patients with 39 CPLs measuring at least 20 mm were enrolled between June 2006 and July 2008 for EUS-cytobrushing and EUS-FNA of CPLs. Demographic, clinical, EUS, cytopathologic, and surgical data were recorded whenever available. Yield of cytology brushings was compared with that of FNA. Procedure morbidity was evaluated after 30 days. The main outcome assessed was yield of intracellular mucin (ICM) on cytobrushing specimens compared with EUS-FNA for the diagnosis of suspected mucinous CPL. RESULTS Cytobrushings were more likely to detect ICM than the EUS-FNA method ( P = 0.001). In three patients with hypocellular FNA, dysplasia was found on cytology brushing and later confirmed by surgical pathology. Significant complications occurred in three patients (8 %): one postbrushing bleeding and two acute pancreatitis. CONCLUSIONS Cytology brushings are more likely to provide an adequate mucinous epithelium specimen than standard FNA and could aid the diagnosis of CPLs in a selective group of patients.

Trainee participation is associated with increased small adenoma detection

BACKGROUND Gastric antral vascular ectasia (GAVE) often results in GI bleeding and chronic anemia. Treatment options are limited and include medical, endoscopic, and surgical therapies. OBJECTIVE To assess the utility of endoscopic mucosal ablative therapy by using the HALO(90) system for patients with GAVE and recurrent bleeding. DESIGN Prospective open-label case series. SETTING Tertiary referral center. PATIENTS Six consecutive patients with GAVE, bleeding, and blood transfusion dependence. MAIN OUTCOME MEASUREMENTS Comparison of preablation and postablation Hb levels and transfusion requirements. To assess the number of ablation sessions needed to stabilize the Hb level and eliminate the need for blood transfusion. RESULTS Six patients, (4 men, mean age 58 years, range 47-65 years) underwent endoscopic mucosal ablation of antral lesions (mean procedure time 29 minutes; mean treatments 1.7, range 1-3). The mean Hb level improved from 8.6 to 10.2 g/dl (mean 2 months after the last ablation). Five of 6 patients are no longer dependent on blood transfusions to maintain a stable Hb level. LIMITATIONS This is a pilot study, with a small number of patients at a single center, with limited patient follow-up. CONCLUSIONS This study suggests that endoscopic mucosal ablation by using the HALO(90) system is a promising treatment option for chronic bleeding related to GAVE.

An evaluation of risk factors for inadequate cytology in EUS-guided FNA of pancreatic tumors and lymph nodes

INTRODUCTION Total pancreatectomy (TP) is associated with significant metabolic abnormalities leading to considerable morbidity. With the availability of modern pancreatic enzyme formulations and improvements in control of diabetes mellitus, the metabolic drawbacks of TP have diminished. As indications for TP have expanded, we examine our results in patients undergoing TP. MATERIALS AND METHODS Retrospective study of 47 patients undergoing TP from January 2002 to January 2008 was performed. Patient data and clinical outcomes were collected and entered into a database. Disease-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS Fifteen males and 32 females with a median age of 70 years underwent TP for non-invasive intraductal papillary mucinous neoplasms (IPMN) (21), pancreatic adenocarcinoma (20), other neoplasm (3), chronic pancreatitis (2) and trauma (1). Median hospital stay and intensive care stay were 11 days and 1 day, respectively. Thirty-day major morbidity and mortality was 19% and 2%, respectively. With a median follow-up length of 23 months, 33 patients were alive at last follow-up. Estimated overall survival at 1, 2 and 3 years for the entire cohort was 80%, 72% and 65%, and for those with pancreatic adenocarcinoma was 63%, 43% and 34%, respectively. Median weight loss at 3, 6 and 12 months after surgery was 6.8 kg, 8.5 kg and 8.8 kg, respectively. Median HbA1c values at 6, 12 and 24 months after surgery were 7.3, 7.5 and 7.7, respectively. Over one-half of the patients required re-hospitalization within 12 months post-operatively. CONCLUSION TP results in significant metabolic derangements and exocrine insufficiency, diabetic control and weight maintenance remain a challenge and readmission rates are high. Survival in those with malignant disease remains poor. However, the mortality appears to be decreasing and the morbidities associated with TP appear acceptable compared with the benefits of resection in selected patients.

The natural history of upper gastrointestinal subepithelial tumors: a multicenter endoscopic ultrasound survey.

BACKGROUND Previous studies examining the effect of fellow participation on adenoma detection rate in colonoscopy have yielded conflicting results, and factors such as adenoma size and location have not been rigorously evaluated. OBJECTIVE To examine whether fellow participation during screening, surveillance, or diagnostic colonoscopy affects overall, size-specific, or location-specific adenoma or polyp detection rate. METHODS This was a retrospective study of 2430 colonoscopies performed in our ambulatory surgical center between September 2006 and December 2007, comparing adenoma and polyp detection rates of colonoscopies performed by fellows with supervising staff endoscopists (n = 318) with colonoscopies performed by staff endoscopists without fellow participation (n = 2112). Study participants included patients who underwent screening, surveillance, or diagnostic colonoscopies in our GI suite. Logistic regression analysis was used to evaluate the association of fellow participation with adenoma and polyp detection. RESULTS There was evidence of a higher rate of small (<5 mm) adenoma detection in colonoscopies with a fellow present (25% vs 17%, P = .001). This remained significant after multiple-testing adjustment (P ≤ .003 considered significant). Findings were similar, although not significant for small polyps (36% vs 29%, P = .007). There was a trend toward increased adenoma detection in colonoscopies with a fellow present compared with those without (30% vs 26%, P = .11). Multivariable adjustment for potentially confounding variables did not alter these associations. LIMITATIONS The study had a retrospective design, and information regarding bowel preparation was not available for 37% of patients. CONCLUSION Fellow involvement was associated with increased detection rates of small adenomas, providing evidence that the presence of a fellow during colonoscopy plays a role in enhancing the effectiveness of the examination.