Dionysios Voros

Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance.

MicroRNAs are a class of non‐coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR‐21, ‐31, ‐122, ‐145, ‐146a, ‐ 200c, ‐221, ‐222 and ‐223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognostic significance. Micro‐RNA expression was assessed by reverse transcription and real‐time PCR (RT‐PCR). Clinicopathological data and survival rates were retrieved and analyzed. According to our results, miR‐21, miR‐31, miR‐122, miR‐221, miR‐222 were significantly up‐regulated in HCC tissues, whereas miR‐145, miR‐146a, miR‐200c, and miR‐223 were found to be down‐regulated. Concerning ICC samples, miR‐21, miR‐31, and miR‐223 were found to be over‐expressed, whereas miR‐122, miR‐145, miR‐200c, miR‐221, and miR‐222 were down‐regulated. Additionally, expression of miR‐21, miR‐31, miR‐122, and miR‐221 in HCC correlated with cirrhosis, while miR‐21 and miR‐221 associated with tumor stage and poor prognosis. In ICC tissues, miR‐21, miR‐31, and miR‐223 were found to be over‐expressed, but no correlation with clinicopathological features was found.

Expression of microRNAs in patients with pancreatic cancer and its prognostic significance.

Objectives Investigation of expression profile of well-established microRNAs in pancreatic adenocarcinoma, and its correlation with clinicopathological factors. Methods Eighty-eight samples of ductal pancreatic adenocarcinoma and 98 control samples were analyzed by real-time polymerase chain reaction for miR-21, miR-31, miR-122, miR-145, miR-146a, miR-155, miR-210, and miR-222 expressions. The results were normalized and then statistically analyzed using nonparametric statistical tests. Results According to our results, miR-21, miR-155, miR-210, miR-221, and miR-222, were overexpressed in diseased tissues than in the control samples, whereas miR-31, miR-122, miR-145, and miR-146a were underexpressed. Additionally, the expressions of miR-21 and miR-155 were associated with tumor stage and poor prognosis. Conclusions The tumorigenic role of miR-21 and miR-155 was confirmed, whereas down-regulation of miR-31, miR-145, and miR-146a, in dispute with current literature, renders necessary the revision of use of microRNAs as biological markers.

MRI of abdominal hydatid disease

Seventy hydatid cysts in 30 patients were studied with magnetic resonance imaging (MRI) and computed tomography (CT); all cases were confirmed surgically. MRI detected all cysts when confined to solid organs, whereas small-sized cysts (≤2 cm) may be missed when located in the peritoneal cavity. Hydatid cysts of less than 3 cm (noncomplicated) present no specific findings of hydatid disease. MRI findings suggesting hydatid disease demonstrate a relatively thick hydatid cyst wall, daughter cysts, and germinal membrane detachment. T2-weighted images proved to be superior to T1 or PD-weighted images in demonstrating hydatid cyst wall thickness, germinal membrane detachment, and daughter cysts. In all spin-echo sequences, the maternal cystic content presented much higher signal intensities than that of daughter cysts. This difference in signal intensity is more obvious in T2 weighted images, except in complicated, infected cases. CT proved to be superior to MRI in demonstrating wall calcifications.

Successful treatment with the mTOR inhibitor everolimus in a patient with Perivascular epithelioid cell tumor

Perivascular epithelioid cell tumor (PEComa) is an extremely rare neoplasm that appears to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites. Malignant PEComas exist but are very rare. These tumors represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. Metastatic PEComa is a rare form of sarcoma for which no effective therapy has been described previously and that has a uniformly fatal outcome. Although there is no known effective therapy, the molecular pathophysiology of aberrant mTOR signaling provides a scientific rationale to target this pathway therapeutically. The difficulty in determining optimal therapy, owing to the sparse literature available, led us to present this case. On this basis, we report a case of metastatic retroperitoneal PEComa treated with an oral mTOR inhibitor, with everolimus achieving significant clinical response.

Enteroatmospheric fistulae--gastrointestinal openings in the open abdomen: a review and recent proposal of a surgical technique.

The occurrence of an enteric fistula in the middle of an open abdomen is called an enteroatmospheric fistula, which is the most challenging and feared complication for a surgeon to deal with. It is in fact not a true fistula because it neither has a fistula tract nor is covered by a well-vascularized tissue. The mortality of enteroatmospheric fistulae was as high as 70% in past decades but is currently approximately 40% due to advanced modern intensive care and improved surgical techniques. Management of patients with an open abdomen and an enteroatmospheric fistula is very challenging. Intensive care support of organs and systems is vital in order to manage the severely septic patient and the associated multiple organ failure syndrome. Many of the principles applied to classic enterocutaneous fistulae are used as well. Control of enteric spillage, attempts to seal the fistula, and techniques of peritoneal access for excision of the involved loop are reviewed in this report. Additionally, we describe our recent proposal of a lateral surgical approach via the circumference of the open abdomen in order to avoid the hostile and granulated surface of the abdominal trauma, which is adhered to the intraperitoneal organs.

A review on the role of microRNA in biology, diagnosis, and treatment of pancreatic adenocarcinoma.

Objectives MicroRNAs are molecules implicated in RNA-RNA interaction, playing a role in cell proliferation and differentiation, as well as in carcinogenesis. Knowledge on their biological features is necessary to understand their role in phenotypic characteristics of pancreatic adenocarcinoma. Methods Review of current literature concerning mechanisms of action, studying methods, implementations, and preclinical trials on pancreatic adenocarcinoma. Results More than 20 microRNAs have been identified, being involved in pancreatic adenocarcinoma biology, affecting tumor growth, metastatic potential, and chemosensitivity. Combinations of microRNAs can be used to differentiate between pancreatic adenocarcinoma and other pancreatic pathologies, as well as to assess prognosis. Manipulations of microRNAs can decrease the rate of growth or reinstall chemosensitivity to certain chemotherapeutic agents. Conclusions The field of microRNAs promises novel diagnostic and therapeutic tools in the management of pancreatic adenocarcinoma.

Pancreatic leakage after pancreaticoduodenectomy: the impact of the isolated jejunal loop length and anastomotic technique of the pancreatic stump.

Objectives To evaluate the impact of the length of the isolated jejunal loop and the type of pancreaticojejunostomy on pancreatic leakage after pancreaticoduodenectomy. Methods One hundred thirty-two consecutive patients who underwent a pancreaticoduodenectomy were studied according to the length of the isolated jejunal loop (short loop, 20-25 cm vs long loop, 40-50 cm) and the type of pancreaticojejunostomy (invagination vs duct to mucosa). Results The use of the long isolated jejunal loop was associated with a significantly lower pancreatic leakage rate compared with the use of a short isolated jejunal loop (4.34% vs 14.2%, P < 0.05). In addition, the use of duct-to-mucosa technique was associated with significantly lower incidence of postoperative pancreatic fistula compared with the invagination technique (4.2% vs 14.5%, P < 0.05). Finally, patients with a short isolated jejunal loop compared with patients with a long loop had increased morbidity (50.7% vs 27.5%, P < 0.05) and prolonged hospital stay (16.3 ± 1.9 days vs 10.2 ± 2.3 days, P < 0.05). Overall mortality rate was 1.5%. Conclusions The use of a long isolated jejunal loop and a duct-to-mucosa pancreaticojejunostomy is associated with decreased pancreatic leakage rate after pancreaticoduodenectomy.

Treatment of hydatid liver disease.

BACKGROUND Echinococcal disease is still a serious problem in certain parts of the world. The liver is the organ affected most frequently. Over recent decades, various reports have been published comparing standard surgical and more conservative modalities for the treatment of the disease. Proper selection among the strategies reported so far could be the most appropriate part of successful patient management. METHODS A thorough review of the most recent reports on the treatment of liver Echinococcus infection, including percutaneous drainage, medical management, and laparoscopic, endoscopic and open surgical approaches has been conducted, focusing on patient outcomes. RESULTS The standard surgical approach, namely partial capsectomy, drainage, and epiploplasty, remains the most frequent operative method. Previous problems such as disease recurrence and a residual cavity seem to be managed optimally with more radical operations such as total pericystectomy. Laparoscopic and endoscopic approaches (endoscopic retrograde cholangiopancreatography and sphincterotomy) appear to have a crucial role, especially when the location of the cyst or the patients status does not permit more radical approaches. Percutaneous computed tomography- or ultrasound-guided drainage appears to be of great value in certain cases. Chemotherapeutic agents remain useful as an adjuvant treatment. CONCLUSIONS Appropriate patient selection and proper use of the various available treatments are of great importance. A tailor-made approach should be employed for each patient. The surgeons experience constitutes a principal criterion. To achieve the best possible results, an interdisciplinary approach should be used in the majority of patients.

Retroperitoneal tumors: Do the satellite tumors mean something?

Background and Objectives: Primary retroperitoneal tumors constitute a rather uncommon disease with an incidence of 2 in 100,000. Local recurrence after surgical resection is reported between 60% and 90% at 10 yr. The aim of this study was to present the problem of satellite tumors around the main tumor mass and their possible relation to local recurrence.

Transhepatic lactate gradient in relation to liver ischemia/reperfusion injury during major hepatectomies.

Hepatectomies performed under selective hepatic vascular exclusion are associated with a series of events culminating in ischemia/reperfusion injury, a state that shares common characteristics with situations known to result in global or regional hyperlactatemia. Accordingly, we sought to determine whether lactate is released by the liver during hepatic resections performed under blood flow deprivation and what relation this has to a possible systemic hyperlactatemic state. After ethical approval, 14 consecutive patients with resectable liver tumors subjected to hepatectomy under inflow and outflow occlusion of the liver were studied. Lactate concentrations were assessed in simultaneously drawn arterial, portal venous, and hepatic venous blood before liver dissection and 50 minutes postreperfusion. Moreover, the transhepatic lactate gradient (hepatic vein − portal vein) was calculated to see if there was net production or consumption of lactate. Before hepatic dissection, the transhepatic lactate gradient was negative, suggesting consumption by the liver. Fifty minutes after reperfusion, this gradient became significantly positive, demonstrating release of lactate by the liver (0.12 ± 0.31 vs. −0.38 ± 0.30 mmol/L, P < 0.05). The magnitude of lactate release correlated with systemic arterial lactate levels at the same time point (r2 = 0.63, P < 0.001). A weaker but significant correlation was demonstrated between the transhepatic lactate gradient postreperfusion and systemic arterial lactate levels 24 hours postoperatively (r2 = 0.41, P = 0.013). A strong correlation between the transhepatic lactate gradient postreperfusion and peak postoperative aspartate aminotransferase values was also demonstrated (r2 = 0.73, P < 0.001). The liver becomes a net producer of lactate in hepatectomies performed under blood flow deprivation. This lactate release can explain some of the systemic hyperlactatemia seen in this context and relates to the extent of ischemia/reperfusion injury. Liver Transpl 12:1825‐1831, 2006.