Banke Agarwal

BACKGROUND: Helicobacter pylori may promote gastric carcinogenesis through increasing gastric epithelial cell proliferation. How H pylori does so is unknown. Programmed, non-necrotic, cell death (apoptosis) occurs throughout the gut and is linked to proliferation. It was hypothesised that H pylori may induce hyper-proliferation through increasing apoptosis. AIM: To measure the effect of H pylori infection on gastric epithelial apoptosis in situ. PATIENTS: Patients with duodenal ulcers treated to eradicate H pylori and patients with H pylori negative non-ulcer dyspepsia. METHODS: Retrospective quantification of apoptotic epithelial cells in situ from formalin fixed biopsy specimens, counted after staining by terminal uridine deoxynucleotidyl nick end-labelling. RESULTS: In the uninfected stomach, apoptotic cells were rare and situated in the most superficial portion of gastric glands (mean 2.9% of epithelial cells). In H pylori infection, they were more numerous and were located throughout the depth of gastric glands, comprising 16.8% of epithelial cells, falling to 3.1% after H pylori eradication, p = 0.017. Apoptotic cell number did not correlate with the degree of histological gastritis. CONCLUSIONS: These results suggest that H pylori induces epithelial apoptosis in vivo. Increased apoptosis may be the stimulus for a compensatory hyperproliferative and potentially preneoplastic response in chronic H pylori infection.

INTRODUCTION: Endoscopic ultrasound (EUS) is now established as a valuable imaging test for diagnosing and staging pancreatic cancer. But, with significant recent improvements in spiral CT scanners, particularly higher resolution and ability to reconstruct 3D images, spiral CT is now increasingly accepted as being better for pancreatic cancer staging. The debate continues, however, about the best diagnostic test or combination of tests in patients with suspected pancreatic cancer. Spiral CT is more readily available than EUS-FNA and, therefore, more frequently used. In this study, we evaluated the use of EUS-FNA in conjunction with spiral CT for suspected pancreatic cancer. METHODS: We retrospectively evaluated 81 consecutive patients who underwent EUS and EUS-FNA for clinical suspicion of a pancreatic cancer from November 2000 to November 2001. All patients had spiral CT with a multiphasic pancreatic protocol using multidetector spiral CT scanners. In all patients, EUS-FNA and spiral CT examinations were performed less than 3 wk apart. RESULTS: Overall, the accuracy of spiral CT, EUS, and EUS-FNA was 74% (n = 60/81, CI 63-83%), 94% (n = 76/81, CI 87-98%), and 88% (n = 73/81, CI 81-96%), respectively, for diagnosing pancreatic cancer. In patients without an identifiable mass on spiral CT, the diagnostic accuracy of EUS and EUS-FNA for pancreatic tumors was 92% (n = 23/25, CI 74-99%). Absence of a focal "mass" lesion on EUS reliably excluded pancreatic cancer irrespective of clinical presentation (NPV 100% n = 5/5, CI 48-100%). The negative predictive value of EUS-FNA was only 22% (n = 2/9, CI 3-60%) in patients with obstructive jaundice and biliary stricture. However, in patients without obstructive jaundice at initial presentation, EUS-FNA was highly accurate (accuracy 97%, n = 33/34, CI 85-100%) and was reliable for ruling out malignancy (NPV 89%, n = 8/9, CI 52-100%). Cytologic assessment of EUS-FNA specimens was 89% accurate for identifying malignancy in suspicious lesions visualized on EUS. CONCLUSIONS: The EUS with FNA can be a valuable adjunct to newer high-resolution multidetector spiral CT for diagnostic evaluation of patients with suspected pancreatic cancer.

Beta-hydroxy-beta-methylglutaryl coA reductase inhibitors (HRIs) inhibit isoprenylation of several members of the Ras superfamily of proteins and therefore have important cellular effects, including the reduction of proliferation and increasing apoptosis. Significant toxicity at high doses has precluded the use of HRIs as a monotherapy for cancers. We therefore studied whether combinations of the HRI lovastatin with standard chemotherapeutic agents would augment apoptosis in colon cancer cells. In the colon cancer cell lines SW480, HCT116, LoVo, and HT29, lovastatin induced apoptosis with differing sensitivity. Pretreatment with lovastatin significantly increased apoptosis induced by 5-fluorouracil (5-FU) or cisplatin in all four cell lines. Lovastatin treatment resulted in decreased expression of the antiapoptotic protein bcl-2 and increased the expression of the proapoptotic protein bax. The addition of geranylgeranylpyrophospate (10 microM) prevented lovastatin-induced augmentation of 5-FU and cisplatin-induced apoptosis; mevalonate (100 microM) was partially effective, whereas cotreatment with farnesyl pyrophosphate (100 microM) had no effect. These data imply that lovastatin acts by inhibiting geranylgeranylation and not farnesylation of target protein(s). Our data suggest that lovastatin may potentially be combined with 5-FU or cisplatin as chemotherapy for colon cancers.

Biliary strictures present a diagnostic challenge, especially when no etiology can be ascertained after laboratory evaluation, abdominal imaging and endoscopic retrograde cholangiopancreatography (ERCP) sampling. These strictures were traditionally classified as indeterminate strictures, although with advances in endoscopic techniques and better understanding of hepato-biliary pathology, more are being correctly diagnosed. The implications of missing a malignancy in patients with biliary strictures-and hence delaying surgery-are grave but a significant number of patients (up to 20%) undergoing surgery for suspected biliary malignancy can have benign pathology. The diagnostic approach to these patients involves detailed history and physical examination and depends on the presence or absence of jaundice, level of obstruction, and presence or absence of a mass lesion. While abdominal imaging helps to find the level of obstruction and provides a 'road map' for further endoscopic investigations, tissue diagnosis is usually needed to make decisions on management. Initially ERCP was the only modality to investigate these strictures but now, with the development of endoscopic ultrasound with fine needle aspiration and the availability of newer techniques such as intraductal ultrasound, single-operator cholangioscopy and confocal laser endomicroscopy, the diagnostic approach to biliary strictures has changed significantly. In this review, we will focus on the decision-making process for patients with biliary strictures and discuss the key decision points that should dictate further diagnostic investigations at each step.