Confocal laser endomicroscopy in diagnosing indeterminate biliary strictures and pancreatic lesions a prospective pilot study.

INTRODUCTION: An accurate histopathological diagnosis of indeterminate biliary strictures and pancreatic lesions is challenging because of insufficient quali-ty of tissue specimen taken during ERCP (brush cytology), cholangioscopy (biopsies) or endosonography (EUS, FNAB). Confocal laser endomicroscopy (CLE) allows virtual histopathological diagnosis with the potential to either replace or increase the diagnostic yield of standard histopathological diagnosis in patients presenting with biliary strictures and pancreatic lesions. The aims of our prospective pilot study were to: 1. Assess the diagnostic yield of standard histopathology compared to CLE in patients referred for cholangioscopy or for EUS of the pancreas; 2. Evaluate the cost of CLE in these indications. METHODS: CLE was performed (during cholangioscopy or EUS), followed by standard tissue sampling. CLE-based diagnosis was compared with standard histopathology/cytology. CLE probe was introduced through the working channel of the cholangioscope or through the FNAB needle. RESULTS: A total of 23 patients were enrolled (12 women, mean age 61 years); 13 patients underwent cholangioscopy and 10 patients underwent EUS. Cholangioscopy: CLE diagnosed correctly all 4 malignant strictures (histology 2 of them only as 2 patients had insufficient quality of the tissue specimen). Agreement between standard histopathology and CLE was achieved in 85 %. EUS: All 3 cases of pancreatic cancer were correctly diagnosed by both CLE and FNAB. All remaining (premalignant and benign) lesions were also correctly diagnosed by both methods. The cost of CLE examination is higher compared to FNAB but comparable with tissue sampling during digital cholangioscopy. CONCLUSION: CLE demonstrated sufficient diagnostic accuracy in patients with indeterminate biliary strictures or pancreatic lesions and, therefore, might improve diagnostic accuracy or even replace standard histopathology in these indications.

Bevacizumab in combination with chemotherapy in the first-line treatment of metastatic colorectal carcinoma.

Colorectal carcinoma (CRC) is a malignancy of worldwide increased incidence. The vast majority of all CRC cases occur in patients older than age 50. The initial stage at the time of diagnosis has a strong influence on the overall survival (OS). According to AJCC sixth edition system, 5-year stage-specific survivals are over 90% in stage I, but only approximately 8% in stage IV [1]. Chemotherapy in combination with biological treatment has improved response rates (RR), with prolongation of progression free survival (PFS) and OS. Important role in treatment of metastatic colorectal carcinoma (mCRC) plays surgical resection of metastases. Multidisciplinary cooperation between medical oncologist, surgeon, radiologist and radiotherapist is necessary to achieve the best therapeutic results. The aim of our analysis was to describe the efficacy of bevacizumab used in combination with chemotherapy in the first-line setting and to evaluate frequency of thromboembolic complications during the treatment. The analysis included 58 patients with mCRC, who have been treated with first-line chemotherapy in combination with bevacizumab at the St. Elizabeth Cancer Institute in Bratislava since 2006 and first assessed for the first therapeutic results in October 2010. The clinical benefit after the treatment represented by overall response rate (ORR) and stable disease (SD) was achieved in 87.93% of patients, and surgical resection of metastases after therapy underwent 12.07% of patients. Median time to progression (TTP) was 8 months and median OS evaluated in October 2011 was 27 months. Mutation status of KRAS gene had no influence on the effectiveness of treatment and BRAF mutations exhibited a strong negative prognostic significance. Thromboembolic complications were present in 17.24%.

STK11/LKB1 germline mutations in the first Peutz-Jeghers syndrome patients identified in Slovakia.

Peutz-Jeghers syndrome (PJS) is characterized by number of hamartomatous polyps in the gastrointestinal tract and by mucocutaneous hypermelanocytic lesions at different sites. Older patients have an increased risk of the cancers of small intestine, stomach, pancreas, colon, esophagus, ovary, testis, uterus, breast and lung. In majority of PJS cases, the germline mutations in serine/threonine kinase STK11/LKB1 gene were found to be associated with disease. Here we report the results of a first mutational screen of STK11/LKB1 in PJS patients characterized in Slovak population. The first patient with unusual carcinoma of duodenum was a sporadic case and carried c.842delC change residing in a mutational C6 repeat hotspot. Neither the polyp nor the tumor of the patient displayed the loss of heterozygosity at the site of mutation suggesting different mechanism involved in the formation of polyp and tumor in this case. The second patient belonged to a three-generation family with typical PJS features but not cancers. Interestingly, the patient displayed concomitant occurrence of adenomatous and hamartomatous polyps. Molecular analysis revealed an IVS2+1A>G mutation that alters the second intron 5' splice site and was shown to lead to aberrant splicing mediated by the U12-dependent spliceosome. The same mutation was present in the 9 affected members of the family but in none of their normal relatives. We also observed novel c. IVS2+61G>A unclassified variant, and recurrent IVS2+24G>T and 3UTR+129C>T polymorphisms. Based on the achieved results, we could offer predictive genetic testing and counseling to other members of the patient's families.