Soeren Torge Mees

The microRNA-200 family--a potential diagnostic marker in hepatocellular carcinoma?

Hepatocellular carcinoma (HCC) represents the main cause of death among patients with cirrhotic liver disease, but little is known about mechanisms of cirrhosis associated carcinogenesis. We investigated the diagnostic impact of microRNA‐200 (miR‐200) family members as important epigenetic regulators of epithelial–mesenchymal transition (EMT) to differentiate between patients with HCC and liver cirrhosis.

MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer

Background:Invasion of the surrounding tissue is part of the metastatic cascade. Here, we examined the invasion of pancreatic ductal adenocarcinoma (PDAC) cells into the mesothelial barrier and identified the related microRNA (miRNA) expression profiles.Methods:The interactions between PDAC cells and mesothelial monolayers were characterised and quantified using a specific time-lapse videomicroscopy assay. Pancreatic ductal adenocarcinoma cells were further evaluated using the adhesion assay, and miRNA, mRNA and protein expressions were determined using microarray, q-RT–PCR and western blots, respectively. These data were correlated with in vivo dissemination scores.Results:Two groups of PDAC cell lines were distinguished by their integration capacity into the mesothelial monolayer using mean elongation factors (MEFs). Adhesion assays showed a concordant relation between adhesive properties and integration capacity. The distant metastases scores were reverse correlated with MEFs. Microarray analysis of these groups revealed that miR-23a and/or miR-24 target for FZD5, HNF1B and/or TMEM92, respectively, and that they are significantly deregulated.Conclusions:MiR-23a and/or miR-24 overexpression leads to gene silencing of FZD5, TMEM92 and/or HNF1B. Their downregulation induces deregulated expression and degradation of E-cadherin and β-catenin causing destabilisation of the cadherin/catenin complex, and altered the expression of Wnt-related genes. We propose a molecular (epi)genetic mechanism by which increased EMT-like cell shape transformation and integration into mesothelial monolayers of PDAC cells can be observed.

Extracorporeal machine perfusion of the pancreas: technical aspects and its clinical implications – a systematic review of experimental models

Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications.

Epigenetic regulation and role of metastasis suppressor genes in pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is distinguished by rapid dissemination. Thus, genetic and/or epigenetic deregulation of metastasis suppressor genes (MSG) is a likely event during early pancreatic carcinogenesis and a potential diagnostic marker for the disease. We investigated 9 known MSGs for their role in the dissemination of PDAC and examined their promoters for methylation and its use in PDAC detection.MethodsMRNA expression of 9 MSGs was determined in 18 PDAC cell lines by quantitative RT-PCR and promoter methylation was analyzed by Methylation Specific PCR and validated by Bisulfite Sequencing PCR. These data were compared to the cell lines’ in vivo metastatic and invasive potential that had been previously established. Statistical analysis was performed with SPSS 20 using 2-tailed Spearman’s correlation with P < 0.05 being considered significant.ResultsComplete downregulation of MSG-mRNA expression in PDAC cell lines vs. normal pancreatic RNA occurred in only 1 of 9 investigated genes. 3 MSGs (CDH1, TIMP3 and KiSS-1) were significantly methylated. Methylation only correlated to loss of mRNA expression in CDH1 (P < 0.05). Bisulfite Sequencing PCR showed distinct methylation patterns, termed constant and variable methylation, which could distinguish methylation-regulated from non methylation-regulated genes. Higher MSG mRNA-expression did not correlate to less aggressive PDAC-phenotypes (P > 0.14).ConclusionsGenes with metastasis suppressing functions in other tumor entities did not show evidence of assuming the same role in PDAC. Inactivation of MSGs by promoter methylation was an infrequent event and unsuitable as a diagnostic marker of PDAC. A distinct methylation pattern was identified, that resulted in reduced mRNA expression in all cases. Thus, constant methylation patterns could predict regulatory significance of a promoter’s methylation prior to expression analysis and hence present an additional tool during target gene selection.

Electrosurgery: what do young surgeons need to know?

The term ‘electrosurgery’ is often used as an umbrella term to describe the different forms of energy used in surgery. Usage of energy occurs in virtually all operations, even more so in laparoscopic surgery, which has become the gold standard for many procedures. Its use, mainly to dissect tissue and control bleeding, has become so common in modern-day surgery that it is an indispensable tool for surgeons. Basic knowledge of the principles of energy usage in surgery is the key to its safe usage. Understanding of electrophysics allows the operator to select the optimal electrosurgical device for a particular set of circumstances and be vigilant to the potential complications associated with the respective instrument. Although popularized since the 1960s, formal teaching of electrosurgical principles was only introduced in Australia in 2002 via the Basic Surgical Skills course and currently in the Australian and New Zealand Surgical Skills Education and Training course. Despite its routine use, operators are found to have obvious deficits in electrosurgery knowledge. This holds true from experienced consultant surgeons to junior surgical registrars. We were keen to identify the level of general knowledge of electrosurgery in our division of surgery and thus a survey was conducted among the general surgery consultants, fellows and registrars. Besides asking for basic information (e.g. position, gender, years of surgical experience, personal complications using electrosurgery, etc.), the questionnaire included 11 multiple choice questions on basic knowledge of electrosurgery, its complications and their prevention. Surprisingly, results were less than satisfactory in all three groups (Table 1). While consultants answered only every second question correctly (53.9%), fellows and registrars did even worse and answered only 41% and 37% of our basic knowledge questions correctly respectively. Asking for electrosurgery-related complications, 69% of the participants (n = 11) have personally caused an injury via an electrosurgical instrument, majority of them in open procedures (54%), and 81% (n = 13) of them know of a colleague who has done so. Given the relevance of this topic to every surgeon and the obvious gaps in knowledge, we wrote this article which intends to provide a quick introduction or a refreshment of fundamental electrosurgical knowledge for the time-strapped junior registrar and consultant alike.

Troubleshooting in laparoscopy: how to treat 'poor image quality'.

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SERPINB5 Promoter Hypomethylation Differentiates Pancreatic Ductal Adenocarcinoma From Pancreatitis.

ObjectivesThe diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging in the setting of pancreatitis. We investigated SERPINB5 for its impact on PDAC tumor biology and its use as a diagnostic marker for PDAC in the setting of pancreatitis. MethodsPatient samples from PDAC primary tumors, PDAC lymph node metastases, and pancreatitis were investigated for SERPINB5 promoter methylation by methylation-specific polymerase chain reaction (PCR). Six PDAC cell lines were investigated in vitro and in vivo using an orthotopic mouse model to generate primary tumors and metastases. SERPINB5 mRNA expression, protein expression, and promoter methylation were determined by quantitative reverse transcriptase–PCR, methylation-specific PCR, and Western Blot. ResultsIn patient samples, detection of an unmethylated SERPINB5 promoter differentiated pancreatitis from PDAC with a sensitivity of 57% and a specificity of 95% (P < 0.001). SERPINB5 was not deregulated in primary tumors versus metastases, but primary tumors without SERPINB5 protein expression had significantly reduced viability (P = 0.02). ConclusionsSERPINB5 seems to assume an oncogenic role in PDAC. In clinical samples, detection of unmethylated SERPINB5 was a specific marker for PDAC even in the context of pancreatitis and may provide the basis for a liquid biopsy option to detect PDAC.

Quality and outcomes of synchronous two-team Ivor-Lewis oesophagectomy: Revisiting a variant technique: Synchronous Ivor-Lewis Oesophagectomy

In 1975, a modification of popular two‐stage Ivor–Lewis oesophagectomy was published with synchronous resection in chest and abdomen. As data on this technique are rare and inconsistent, we aimed to investigate safety, feasibility, and outcome of this approach.

Population-based analysis of 4113 patients with acute cholecystitis: defining the optimal time point for laparoscopic cholecystectomy.

To the Editor: W e read with interest the recent study by Banz et al,1 which evaluated the most favorable time point for laparoscopic cholecystectomy in the setting of acute cholecystitis using the Swiss Association of Laparoscopic and Thoracoscopic Surgery prospective database. The topic is conversely debated in the current literature where no strong consensus for a single approach exists and most authors advocate intervention either immediately or 6 weeks after diagnosis of acute cholecystitis. In the present study, the authors restrict themselves to the investigation of an early time interval for laparoscopic cholecystectomy, ranging from day zero to day 6 after admission. They demonstrated a significantly better outcome for patients operated within 48 hours after admission when compared with those operated on day 6 after admission. The benefit was found in lower intraand postoperative complication rates, lower conversion and reoperation rates, and shorter postoperative hospital stays. Although the collective of 4113 patients is formidable, its gender composition differs from that found in most countries for acute cholecystitis in that the male sex was distinctly overrepresented. Thesbjerg et al3 demonstrated that male sex is associated with