Michael Papadakis

Combined analysis of KRAS and PIK3CA mutations, MET and PTEN expression in primary tumors and corresponding metastases in colorectal cancer

Metastasis is the main cause of mortality in patients with colorectal cancer. However, most of the targeted therapies and predictive molecular biomarkers were developed based mainly on primary tumors. The current study was conducted to determine the degree of discordance between potential predictive and/or prognostic molecular markers in primary colorectal tumors and corresponding metastases, as this could have an impact on the efficacy of targeted therapies in the advanced colorectal cancer. KRAS, PIK3CA and BRAF mutations were determined by Sanger sequencing and mutant-enriched polymerase chain reaction (PCR) assays in 83 paired samples, MET gene copy number by quantitative PCR in 59, MET expression by immunohistochemistry in 73 and nuclear and cytoplasmic expression of PTEN by immunohistochemistry in 78 and 71 pairs, respectively. A certain degree of discordance between primary tumors and corresponding metastases was demonstrated for all examined biomarkers except BRAF mutations. PIK3CA exon 9 mutations in primary tumors and loss of PTEN nuclear expression in metastases correlated with KRAS mutations. KRAS wild-type status in primary tumors was associated with loss of PTEN cytoplasmic expression and high gene copy number of MET. Survival and clinical data were available for 68 patients. The multiple regression analysis revealed that the right-sided tumor localization and overexpression of MET were associated with shorter overall survival.

EUS - Fine- Needle Aspiration Biopsy (FNAB) in the Diagnosis of Pancreatic Adenocarcinoma: A Review.

Solid masses of the pancreas represent a variety of benign and malignant neoplasms of the exocrine and endocrine tissues of the pancreas. A tissue diagnosis is often required to direct therapy in the face of uncertain diagnosis or if the patient is not a surgical candidate either due to advanced disease or comorbidities. Endoscopic ultrasound (EUS) is a relatively new technology that employs endoscopy and high-frequency ultrasound (US). EUS involves imaging of the pancreatic head and the uncinate from the duodenum and imaging of the body and tail from the stomach. It has been shown to be a highly sensitive method for the detection of pancreatic masses. It is superior to extracorporeal US and computed tomographic (CT) scans, especially when the pancreatic tumor is smaller than 2-3 cm. Although EUS is highly sensitive in detecting pancreatic solid masses, its ability to differentiate between inflammatory masses and malignant disease is limited. Endoscopic retrograde cholangiopancreatography (ERCP) brushing, CT-guided biopsies, and transabdominal ultrasound (US) have been the standard nonsurgical methods for obtaining a tissue diagnosis of pancreatic lesions, but a substantial false-negative rate has been reported. Transabdominal US-guided fine-needle aspiration biopsy (US-FNAB) has been used for tissue diagnosis in patients with suspected pancreatic carcinoma. It has been shown to be highly specific, with no false-positive diagnoses. With the advent of curvilinear echoendoscopes, transgastric and transduodenal EUS-FNAB of the pancreas have become a reality EUS with FNAB has revolutionized the ability to diagnose and stage cancers of the gastrointestinal tract and assess the pancreas. Gastrointestinal cancers can be looked at with EUS and their depth of penetration into the intestinal wall can be determined. Any suspicious appearing lymph nodes can be biopsied using EUS/FNAB. The pancreas is another organ that is well visualized with EUS. Abnormalities such as tumors and cysts of the pancreas can be carefully evaluated using EUS and then biopsied with FNAB. There are many new applications of EUS using FNAB. Researchers are looking to deliver chemotherapeutics into small pancreatic cancers and cysts. Nerve blocks using EUS/FNAB to inject numbing medicines into the celiac ganglia, a major nerve cluster, are now routinely performed in patients with pain due to pancreatic cancer. The aim of this study is to perform a review of the literature regarding the usefulness of EUS/FNAB in the diagnosis of pancreatic adenocarcinoma.

Apoptosis and cell proliferation correlated with tumor grade in patients with ampullary carcinoma.

OBJECTIVE To evaluate apoptosis and cell proliferation on cytologic specimens (smears) from endoscopic retrograde cholangiopancreatography in patients with ampulary carcinoma and to correlate that relationship with the grade of the tumors. STUDY DESIGN Forty patients (23 males and 17 females) aged 45-81 who underwent endoscopic retrograde cholangiopancreatography were diagnosed by cytology as having ampullary adenocarcinoma and the diagnoses were confirmed histologically after an operation. All smears were stained using Papanicolaou and Giemsa stain. Apoptosis was assessed using terminal digoxigenin-labeled dUTP nick-end labeling (TUNEL assay) and cell proliferation using MIB-1 monoclonal antibody by the alkaline phosphatase method. RESULTS The TUNEL indices were 0.4 +/- 0.07, 0.91 +/- 0.33 and 3.1 +/- 0.9 in well, moderate and poorly differentiated ampullary carcinoma, respectively. The differences in both TUNEL and MIB-1 labeling indices were statistically significant between well, moderately and poorly differentiated ampullary carcinoma, and a positive correlation was found between TUNEL and the MIB-1 indices. CONCLUSION Apoptosis (cell death) and cell proliferation increase as the grade of the differentiation decreases in ampullary carcinoma, suggesting a rapid turnover of the tumor cells with lower grates of differentiation, and apoptosis may play an important role in the growth of the tumors in patients with ampullary carcinomas.

Engineering of Porphyrin Molecules for Use as Effective Cathode Interfacial Modifiers in Organic Solar Cells of Enhanced Efficiency and Stability

In the present work, we effectively modify the TiO2 electron transport layer of organic solar cells with an inverted architecture using appropriately engineered porphyrin molecules. The results show that the optimized porphyrin modifier bearing two carboxylic acids as the anchoring groups and a triazine electron-withdrawing spacer significantly reduces the work function of TiO2, thereby reducing the electron extraction barrier. Moreover, the lower surface energy of the porphyrin-modified substrate results in better physical compatibility between the latter and the photoactive blend. Upon employing porphyrin-modified TiO2 electron transport layers in PTB7:PC71BM-based organic solar cells we obtained an improved average power conversion efficiency up to 8.73%. Importantly, porphyrin modification significantly increased the lifetime of the devices, which retained 80% of their initial efficiency after 500 h of storage in the dark. Because of its simplicity and efficacy, this approach should give tantalizing glimpses and generate an impact into the potential of porphyrins to facilitate electron transfer in organic solar cells and related devices.

Cytology of Pericardial Effusion due to Malignancy.

Abstract Background. Malignant pericardial effusion occurs in one tenth of all cancers. It is a very serious disorder that is mainly a secondary process due to metastasis because primary neoplasms of the pericardium such as mesotheliomas, sarcomas being exceedingly rare. Pericardial effusions with a cardiac tamponade constitute a surgical emergency and the pericardiocentesis represents the first class therapeutic recommendation. Pericardial effusion specimens are uncommon and to the best of our knowledge the current study is the largest systematic evaluation of pericardial fluid cytology performed to date. Material and Methods. Pericardial effusion specimens from 145 patients collected over a 10 year period were studied by cytology and results were compared with pericardial histology results. The minimum pericardial fluid volume used for adequate cytologic diagnosis in these patients was more than 60 mL. Results. Cytological diagnosis revealed malignant pericardial exudates in 100% of the studied patients. There was no any false negative result in comparison with histology. Conclusions. Cytology provides an immediate and accurate means of diagnosis. Immunocytology is very important in the diagnostic evaluation.

Abdominal primary extra-gastrointestinal stromal tumor (E-GIST). A cytologic diagnosis in ascitic fluid.

Dear Editor, We present a case of a primary abdominal Extra-gastrointestinal stromal tumor (E-GIST) in a75 years old female patient. E-GISTs are rare, non-epithelial, mesenchymal tumors arising from the soft tissues of the abdomen - mesentery and retroperitoneum. These tumors are histologically and cytologically similar to the stromal tumors of gastrointestinal tract, composed of round or fusiform cells or a mixture of both in a myxoid background. The recognition of these tumors is important because of their aggressive biological behavior, the metastatic potential and the high rate of recurrence.