Panagis M. Lykoudis

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.

Global Consequences of Liver Ischemia/Reperfusion Injury

Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organs post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion.

Tumour budding is a strong and independent prognostic factor in pancreatic cancer

INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that escapes detection and resists treatment. Tumour budding, defined as the presence of de-differentiated single tumour cells or small cell clusters at the invasive front of gastrointestinal carcinomas like colorectal, oesophageal, gastric and ampullary, is linked to adverse prognosis. Tumour budding has not yet been reported in PDAC. AIM To assess the frequency and prognostic impact of tumour budding in PDAC. METHODS Whole-tissue sections of 117 PDACs with full clinico-pathological and follow-up information, including postoperative therapy, were stained using a pancytokeratin marker. Tumour budding was assessed in 10 high-power fields (HPFs) by two pathologists. High-grade budding was defined as an average of >10buds across 10HPFs. Measurements were correlated to patient and tumour characteristics. The study was performed according to the REMARK guidelines. RESULTS Inter-observer agreement was considered strong (ICC=0.72). Low-grade budding was observed in 29.7% and high-grade budding in 70.3% cases. High-grade budding was linked to advanced pT classification (p=0.0463), lymphatic invasion (p=0.0192) and decreased disease-free (p=0.0005) and overall survival (p<0.0001). There was no association with pN, pM, R-status or blood vessel invasion. In multivariate analysis, the prognostic effect of tumour budding was independent of lymph node metastasis, lymphatic invasion and R-status (p<0.0001; HR (95% CI): 3.65 (2.1-6.4)). CONCLUSIONS Our results show that high-grade tumour budding occurs frequently in PDAC and is a strong, independent and reproducible, highly unfavourable prognostic factor that could be used to guide future individualised therapeutic approaches.

Systematic review of surgical management of synchronous colorectal liver metastases

The optimal management of colorectal cancer with synchronous liver metastases has not yet been elucidated. The aim of the present study was systematically to review current evidence concerning the timing and sequence of surgical interventions: colon first, liver first or simultaneous.

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.

Contrast-Enhanced Color Doppler Ultrasonography for Preoperative Evaluation of Sentinel Lymph Node in Breast Cancer Patients

Background: Sentinel lymph node (SLN) biopsy is the standard of care for breast cancer patients with non-palpable axillary lymph nodes. We evaluated the usefulness of contrast-enhanced ultrasonography in preoperative detection of malignant SLNs. Methods: 50 patients with breast cancer (median age: 60 years) underwent a color power Doppler ultrasonography with intravenous contrast (Sonovue®) preoperatively, and findings suggestive of metastatic disease to the SLN were documented. The final histopathological report and the radiological preoperative record were compared. Finally, the sensitivity, specificity and diagnostic accuracy of this evolving diagnostic modality were calculated. Results: Contrast-enhanced ultrasound scan identified a negative SLN in the axilla of 27 patients and final histopathology was negative for 30 cases in total, so negative predictive value was calculated as 90% and positive predictive value was 75%. Overall sensitivity was 83.33% and specificity was 84.38%. Moreover, the ability of contrast-enhanced ultrasound to differentiate between SLN status was only statistically significantly correlated with the actual final histopathological report (p < 0.001), while successful ultrasound prediction was not correlated with any factor. Conclusions: SLN status can be evaluated preoperatively using contrast-enhanced color Doppler ultrasonography with high accuracy.

Effect of infliximab on the healing of intestinal anastomosis. An experimental study in rats

BACKGROUND AND AIM Infliximab is effective in the induction and maintenance of remission in Crohns disease. Whether, the perioperative administration of anti-TNF-a compromises intestinal healing leading to anastomotic failure and increased risk of postoperative complications, remains controversial. The aim of the study was to evaluate the effect of Infliximab on intestinal anastomosis healing. METHODS Fifty six wistar rats were divided into 4 groups: (a) 20 rats were subjected to excision of part of the terminal ileum followed by anastomosis which was evaluated on the 3rd or 7th postoperative day; (b) 20 rats received Infliximab and thereafter, the same surgical protocol as group (a) was followed; (c) 8 rats received Infliximab and served as relative control group; and (d) 8 served as absolute control group. Bursting pressure was used for testing intestinal healing. Additionally, the anastomoses were examined macroscopically, histologically and immunohistochemically for TGFb1, MMP1, MMP2 and Collagen V. The results were confirmed by Western blot analysis. RESULTS There were no significant differences in bursting pressures and septic intra-abdominal events among non-Infliximab (a) and Infliximab-treated (b) groups. Infliximab-treated (b) group showed mild to moderate inflammation, whereas the non-Infliximab (a) group exhibited severe inflammation. Expression of TGFb1, MMP2 and collagen V was significantly higher in the Infliximab-treated (b) group. CONCLUSION Infliximab seems to influence intestinal healing in terms of less inflammatory activity and higher tissue remodeling activity.

Subcutaneous granular cell tumour of the lumbar region.

Granular cell tumour (GCT), also known as Abrikossoff tumour, is an uncommon neoplasm, probably of neural origin derived from Schwann cells. It usually presents as a subcutaneous solitary asymptomatic nodule. It has been the subject of much debate in the literature concerning the tumour origin and the association with other malignancies. We report a case of subcutaneous GCT in the lumbar region in a 31-year-old Caucasian male. Although they are a rare entity, GCTs should be considered in the differential diagnosis of the subcutaneous soft tissue tumours. Surgical removal with wide margins is the treatment of choice as malignant changes have been reported after long-term follow-up.

Solitary adrenal metastasis from esophageal adenocarcinoma: a case report and review of the literature.

Introduction. In patients with extra-adrenal malignancy, an adrenal mass necessitates investigating the possibility of metastatic tumor. Curable adrenal metastasis are considered as a rare event. Case report. A 52-year-old male suffering from lower esophageal adenocarcinoma with a solitary left adrenal metastasis is presented herein, who underwent concomitant transhiatal esophagectomy and left adrenalectomy. The patient remains disease-free 18 months later. Discussion. Adrenal metastases mostly occur in patients with lung, kidney, breast, and gastrointestinal carcinomas. Primary esophageal adenocarcinoma gives adrenal metastatic deposits according to autopsy series with an incidence of about 3%–12%. When no other evidence of metastatic disease in cancer patients exists, several authors advocate adrenalectomy with curative intent. Isolated cases of long-term survival after resection of solitary adrenal metastasis from esophageal adenocarcinoma, like in our case, have been reported only as case reports. Conclusion. This study concludes that surgical resection may result in survival benefit in selected patients with solitary adrenal metastasis from esophageal adenocarcinoma.

Role of colectomy in preventing recurrent primary sclerosing cholangitis in liver transplant recipients

AIM To study the published evidence on the impact of colectomy in preventing recurrent primary sclerosing cholangitis (rPSC). METHODS An unrestricted systematic literature search in PubMed, EMBASE, Medline OvidSP, ISI Web of Science, Lista (EBSCO) and the Cochrane library was performed on clinical studies investigating colectomy in liver transplantation (LT) recipients with and without rPSC in the liver allograft. Study quality was evaluated according to a modification of the methodological index for non-randomized studies (MINORS) criteria. Primary endpoints were the impact of presence, timing and type of colectomy on rPSC. Overall presence of inflammatory bowel disease (IBD), time of IBD diagnosis, posttransplant IBD and immunosuppressive regimen were investigated as secondary outcome. RESULTS The literature search yielded a total of 180 publications. No randomized controlled trial was identified. Six retrospective studies met the inclusion criteria of which 5 studies were graded as high quality articles. Reporting of IBD was heterogenous but in four publications, either inflammatory bowel disease, ulcerative colitis or in particular active colitis post-LT significantly increased the risk of rPSC. The presence of an intact (i.e., retained) colon at LT was identified as risk factor for rPSC in two of the high quality studies while four studies found no effect. Type of colectomy was not associated with rPSC but this endpoint was underreported (only in 33% of included studies). Neither tacrolimus nor cyclosporine A yielded a significant benefit in disease recurrence of primary sclerosing cholangitis (PSC). CONCLUSION The data favours a protective role of pre-/peri-LT colectomy in rPSC but the current evidence is not strong enough to recommend routine colectomy for rPSC prevention.