Current status of molecular markers for early detection of sporadic pancreatic cancer

Pancreatic cancer (PC) is a highly lethal malignancy with near 100% mortality. This is in part due to the fact that most patients present with metastatic or locally advanced disease at the time of diagnosis. Significantly, in nearly 95% of PC patients there is neither an associated family history of PC nor of diseases known to be associated with an increased risk of PC. These groups of patients who comprise the bulk of PC cases are termed as "sporadic PC" in contrast to the familial PC cases that comprise only about 5% of all PCs. Given the insidious onset of the malignancy and its extreme resistance to chemo and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of PC, specifically aiming at the sporadic PC cohort. However, while several studies have established that asymptomatic individuals with a positive family history of PC and those with certain heritable syndromes are candidates for PC screening, the role of screening in identifying sporadic PC is still an unsettled question. The present review attempts to assess this critical question by investigating the recent advances made in molecular markers with potential use in the early diagnosis of sporadic PC - the largest cohort of PC cases worldwide. It also outlines a novel yet simple risk factor based stratification system that could be potentially employed by clinicians to identify those individuals who are at an elevated risk for the development of sporadic PC and therefore candidates for screening.     

Prevention of pancreatic reactions by bolus somatostatin administration in patients undergoing endoscopic retrograde cholangio-pancreatography and endoscopic sphincterotomy

Mild pancreatitis is a common complication of endoscopic retrograde cholangio-pancreatography (ERCP) and endoscopic sphincterotomy. Knowing that a bolus injection of natural somatostatin (SRIF) dramatically reduces pancreatic secretion, a study was conducted in 33 subjects undergoing invasive diagnostic procedures. A placebo (n = 16) or SRIF (n = 17; 4 micrograms/kg) were injected before cannulation. Enzymatic rise was observed in 16 (94%) subjects receiving placebo and in 8 (50%) injected previously with SRIF. In the former group 65% reported abdominal pain whereas only 19% had this complaint in the SRIF series. Results suggest that a bolus injection of SRIF may attenuate pancreatic irritation caused by diagnostic procedures or sphincterotomy.     

Real‐time endoscopic Raman spectroscopy for in vivo early lung cancer detection

Currently the most sensitive method for localizing lung cancers in central airways is autofluorescence bronchoscopy (AFB) in combination with white light bronchoscopy (WLB). The diagnostic accuracy of WLB + AFB for high grade dysplasia (HGD) and carcinoma in situ is variable depending on physician's experience. When WLB + AFB are operated at high diagnostic sensitivity, the associated diagnostic specificity is low. Raman spectroscopy probes molecular vibrations and gives highly specific, fingerprint‐like spectral features and has high accuracy for tissue pathology classification. In this study we present the use of a real‐time endoscopy Raman spectroscopy system to improve the specificity. A spectrum is acquired within 1 second and clinical data are obtained from 280 tissue sites (72 HGDs/malignant lesions, 208 benign lesions/normal sites) in 80 patients. Using multivariate analyses and waveband selection methods on the Raman spectra, we have demonstrated that HGD and malignant lung lesions can be detected with high sensitivity (90%) and good specificity (65%).

     

Improving diagnostic yield of biliary brushings cytology for pancreatic cancer and cholangiocarcinoma

Biliary brushings are currently the best accepted method to obtain a cytological diagnosis of pancreatic cancer or cholangiocarcinoma. The technique has good specificity but poor sensitivity. Two dedicated pathologists reviewed 137 consecutive biliary brushings from 127 patients between February 1997 and February 2000. The ultimate diagnosis was determined by review of radiology, operative diagnosis and patient outcome. The sensitivity, specificity, positive predictive value and negative predictive value of the original results and the review results were calculated and compared. Additional diagnostic categories 'suspicious' and 'atypical possibly benign' were included on review. After review, the sensitivity improved from 49.4% to 89.0% and the specificity remained 100%. The use of the additional diagnostic category 'suspicious' increased the sensitivity to 90.4%, at the expense of a fall of the specificity to 66.7%. We conclude that review by two dedicated pathologists and additional diagnostic categories can improve the diagnostic accuracy of biliary brushings.     

Carcinoma of buccal mucosa in smokeless tobacco users: a preliminary study of the use of cytology for early detection

A type of smokeless tobacco, known as Maras powder, is widely used in lieu of cigarettes in the south-eastern region of Turkey. In the present study, we evaluated cytological smears obtained from the lesion of lower lip mucosa of 80 smokeless tobacco users. There were severe epithelial abnormalities in seven out of the 80 subjects. Punch biopsies from these cases disclosed dysplasia in three cases, carcinoma in situ in two, and carcinoma in the other two cases. There was mild dysplasia in two punch biopsies of the remaining 73 cases. Oral cancer in tobacco powder users appeared to be related to the length of use, as it was observed only in subjects with 15 or more years of exposure.     

Evaluation of brushing cytology in the diagnosis of Helicobacter pylori gastritis

OBJECTIVE: To evaluate clinical utility of rapid urease test (RUT), brash cytology and histology for detecting Helicobacter pylori. STUDY DESIGN: Brush cytology materials were obtained from the antrum of the stomach in 109 patients who suffered from dyspepsia and were candidates for endoscopy. RUT and histology with hematoxylin-eosin staining were performed. Infection status was established by observation of typical HP in cytology or biopsy. RESULTS: A total of 78% ofpatients were diagnosed as positivefor HP organisms using brush cytology; 66% had histologic results positive for HP and 59% for RUT. Observation of typical organism by cytology or histology was the gold standard; 3 tests results were compared. Sensitivity of brush cytology (95%) was higher than that of histology (80.5%) and RUT (72%). CONCLUSION: Gastric brushing cytology provides a sensitive, inexpensive, accurate and easy technique for rapid detection of HP infection. When additional information on severity of mucosal damage or presence of cell atypias is not necessary, histologic examination can be omitted; a cost-effective strategy for assessing HP status might consist of taking antral biopsies, the former for RUT, and performing brush cytology slides, which should be stained and examined only when the RUT result is negative.     

The role of brushing cytology in the diagnosis of gastric malignancy

The results of endoscopic biopsy and brushing cytology in 234 consecutive patients with established histologic diagnoses of discrete gastric lesions were analyzed. A histopathologic diagnosis of malignancy, established by independent means, was made in 74 patients. Brushing cytology was positive for malignancy in 63, a diagnostic sensitivity of 85%. Endoscopic biopsy was positive in 64, a diagnostic sensitivity of 86%. The sensitivity for combined cytology and biopsy was 91%, which was not significantly greater than for biopsy alone (P = .6). Cytology yielded false-positive results in 5 of 160 patients (3.1%) with confirmed benign disease. There were no false-positive biopsy reports. Although both brushing cytology and biopsy have high diagnostic sensitivities, based on the findings of this study, the routine addition of cytology to biopsy in the endoscopic evaluation of gastric lesions is not recommended. Cytology could be reserved for situations in which difficulty is encountered in obtaining adequate tissue for histologic examination and for cases with a high suspicion of malignancy that have yielded negative biopsies.     

Diagnosis of metastatic adamantinoma of the tibia by pulmonary brushing cytology

A case of adamantinoma of the tibia metastatic to the lung is reported in which the metastatic lesion was initially diagnosed by pulmonary brushing cytology. The cytologic features, including clusters of small cells with either prominent nucleoli or spindle-shaped hyperchromatic nuclei, appear to be distinctive enough to differentiate this lesion from other metastatic malignant tumors of the lung.     

Do we use the appropriate controls for the identification of informative methylation markers for early cancer detection?

It is possible to miss potential DNA methylation markers of tumorigenesis because of the initial filtering of profiling results on the basis of inappropriate controls.     

Rapid detection of rectal cancer by gloved digital-scrape cytology

To evaluate the use of cytology for the rapid detection of rectal cancer, 39 suspected cases of carcinoma of the rectum and anal canal and 7 age- and sex-matched control cases were studied by the gloved digital-scrape method. The cytologic findings were then correlated with the histopathologic diagnoses. Of 30 evaluable cases with follow-up, a correct cytologic diagnosis was made in 28 cases (93.4%), with 1 false-negative diagnosis (3.3%) and 1 false-positive diagnosis (3.3%). Gloved digital-scrape cytology is very simple, quick and inexpensive and can be carried out an out-patient basis without any complications.