Evaluation of protein expression and DNA methylation profiles detected by pyrosequencing in invasive breast cancer.

Breast carcinoma is the most common cancer with high mortality caused by metastatic disease. New molecular biomarkers predicting the tumour's metastatic potential would therefore improve metastasis prevention and personalised care. The aim of the study was to investigate the relationship between DNA methylation levels in invasivity and metastasising associated genes with aberrant protein expression and also to evaluate whether a similar DNA methylation level is present in the tumour and circulating cell-free DNA for utilising plasma DNA methylation as prognostic biomarker. By using pyrosequencing, we analysed DNA methylation levels of 11 genes, namely APC, ADAM23, CXCL12, ESR1, PGR B, CDH1, RASSF1A, SYK, TIMP3, BRMS1 and SOCS1 in tumour, plasma and peripheral blood cells from 34 patients with primary breast cancer, as well as plasma and peripheral blood cells from 50 healthy controls. Simultaneously, the expression of related proteins in paraffin-embedded tumour samples was evaluated by immunohistochemistry. Statistical analysis was performed by SPSS statistics 15.0 software. Tumour DNA hypermethylation was found in most commonly methylated RASSF1A (71.9%), APC (55.9%), ADAM23 (38%) and CXCL12 (34.4%) genes with methylation levels up to 86, 86, 53 and 64 %, respectively. In tumours, significantly higher methylation levels were found in nine genes, compared with the patients´ peripheral blood cell DNA. Furthermore, in patients methylation levels in peripheral blood cell DNA were significantly higher than in controls in CXCL12, ESR1 and TIMP3 genes, but the values did not exceed 15%. On the other hand, no correlations were observed in patients between DNA methylation in tumours and cell-free plasma DNA. Moreover, in patients and controls nearly identical values of cumulative DNA methylation (43.6 % ± 20.1 vs. 43.7 % ± 15.0) were observed in plasma samples. A variable spectrum from high to none expressions presented in tumour tissues in all of the proteins evaluated, however in APC and CXCL12 genes a visible decreasing trend of mean DNA methylation level with increasing expression of the corresponding protein was observed. The DNA methylation profiles manifested in our group of breast carcinomas are cancer specific, but they are not the only cause that affects the silencing of evaluated genes and the decrease of relevant protein products. The clinical utility of DNA methylation testing in peripheral blood cell DNA for cancer diagnosis and therapy need to be further investigated.

Portomesenteric vein gas and pneumatosis intestinalis--a rare complication after neoadjuvant radiochemotherapy in oesophageal cancer.

Portomesenteric vein gas and pneumatosis intestinalis is most commonly caused by mesenteric ischemia and bowel necrosis but may have a variety of other causes. The etiology is multifactorial and the clinical presentation is variable. The diagnosis is based on a combination of clinical suspicion and radiographic findings. The finding of hepatic portal venous gas alone is not an indication for emergent exploration. We report portomesenteric venous gas as a rare complication after neoadjuvant radiochemotherapy of the oesophageal cancer (Fig. 3, Ref. 12).

[Postoperative ileus--pathophysiology, prevention and treatment (overview)]. / Pooperacný ileus--patofyziológia, prevencia a liecba (prehl'adová práca).

Postoperative ileus is relatively frequent postoperative complication after major abdominal operations, extending the patient's hospital stay and thus the cost of hospitalization. Multimodal fast-tract-access surgery is increasingly being implemented into clinical practice allows for an early resumption of intestinal activity and shortening hospital stays after uncomplicated major gastrointestinal operations.

Specific aspects of acute pancreatitis.

Acute pancreatitis (AP) is still a disease with a significant mortality rate, mainly concerning the severe forms of this disease. Mortality in acute pancreatitis has 2 peaks. The first peak is caused by systemic inflammatory response syndrome (SIRS), which takes place in the first week of the disease. Sepsis is responsible for a second peak. It begins 1 to 3 weeks after the onset of acute pancreatitis and is caused by pancreatic superinfection. Sepsis as a result of infected pancreatic necrosis is the most serious complication in late phase of severe acute pancreatitis (SAP) and contributes to the high mortality rate of this disease. This complication is thought to be a result of the bacterial translocation from the gastrointestinal tract. The damage of the microvessels and the subsequent onset of systemic cascade reactions plays also an important role during acute pancreatitis. Recent experimental data suggest also the role of nervous system in etiopathogenesis of acute pancreatitis. We assume that the diagnostic and treatment strategy can not improve without a thorough knowledge of the physiology and patophysiology of acute pancreatitis. Therefore the aim of this paper is to highlight certain specific situations of high importance that are activated in the human organism during acute pancreatitis (Ref. 100).

Enterovesical fistulas in Crohn's disease.

BACKGROUND: Crohn's disease is a chronic inflammatory disease of the bowel, that may affects the urinary system. Although fistula formation has been reported in up to 35% patients suffering from Crohn's disease, urinary fistulas affect only 2 to 8% patients. PATIENTS AND METHODS: Authors have done a retrospective study with the aim to investigate the incidence of enterovesical fistulas in patients admitted due to Crohn's disease to the IInd Department of Surgery of the Comenius University Medical School and Department of Surgery of University Hospital Nitra during 10 years long period. RESULTS: The overall incidence of enterovesical fistulas in our clinical material was 6.83%. All patiens underwent elective surgery. There were no serious postoperative complication. A two stage approach was necessary due to severe inflammation in one patient. Severity of inflammation decreased later on, after treatment with anti TNF *, which allowed subsequent elective surgery. CONCLUSION: Authors consider elective surgery as a treatment of choice in the managenet of enterovesical fistulas in Crohn's disease. Surgery is effective and safe (Fig. 2, Ref. 3). Full Text (Free, PDF) www.bmj.sk.

Septic complications of acute pancreatitis.

Acute pancreatitis (AP) is a potentially lethal disease. There are numerous studies published on acute pancreatitis. This article presents the results of research of many scientists in the field of acute pancreatitis. The main aim of this article is to present the possible septic complications of acute pancreatitis, its diagnostic and treatment modalities. Early morbidity and mortality are the result of activation of mediators with failure of circulation and other organ systems. The overall mortality of patients with acute necrotising pancreatitis is in the range of 10-15 %. Secondary pancreatic infection and sepsis develop in 40-70 % of patients with 80 % mortality. Pancreatic infection is caused by bacterial contamination of pancreatic necrosis. Infection is usually recorded in the second week of the disease in 24 % and in 71 % during the fourth week of the disease. The incidence of secondary infection and sepsis correlates with the extent of pancreatic necrosis. The prevention of infection and sepsis by systemic administration of antibiotics is considered a principal step in the therapy of acute pancreatitis (Ref 62).

Cystic renal cell carcinoma--rare clinical finding. Radiographic variations of tumor/cyst appearance and further diagnostic work-up.

OBJECTIVES: To review the cases of cystic renal cell carcinoma and multilocular cystic nephroma, point out the radiographic variations and define further diagnostic work-up. MATERIALS AND METHODS: Between 2003 and 2005 5 patients with suspected cystic renal cell carcinoma were treated surgically (1 pt underwent radical nephrectomy, 1 pt laparoscopic cyst decortication, 3 pts ablation), 2 patients with multilocular cystic nephroma underwent ultrasound guided biopsy. RESULTS: Histopathologic examination confirmed cystic renal cell carcinoma (CRCC) T1aNOM0 Fuhrman grade 1 in 3 cases, T1bN0M0 Fuhrman grade 2 in one case. One patient with suspected tumor inside the cyst wall who underwent laparoscopic cyst decortication was excluded (final histology confirmed organized hematoma in the cyst wall). Biopsy in 2 patients with multilocular cystic nephroma did not confirm the presence of malignant cells. The mean tumor size was 4.2 cm (range 3.7 to 5.5) for CRCC and 4.7 cm (range 4 to 4.5 cm) for multilocular cystic nephroma. All 4 cases of CRCC were clear cell type. CONCLUSION: In conclusion according to the data described and from our study, tumor/cyst co-existence requires further surgical exploration in group 2, 3, 4. Small cystic renal cell carcinomas up to 4 cm in diameter have usually favourable pathology and prognosis, which offers the minimally invasive nephron-sparing treatment options such as excision, ablation or partial nephrectomy (Fig. 9, Ref. 18).

Portal vein thrombosis uncommon clinical picture.

The authors described a case of the patient of the idiopatic group of PVT. Due to only a few symptoms, the diagnosis was established late. This was confirmed by the fact, that the patient was not hospitalized. So it was an atypical case of chronic PVT. Portal vein thrombosis belongs to rare clinical conditions. Early diagnosis based on modern technique is possible only if we keep this condition in mind (Tab. 1, Fig. 1, Ref. 23).

Valsalva leak point pressure predicts outcome after transobturator suburethral tape implantation--fact or fiction?

INTRODUCTION AND OBJECTIVES: The aim of the study was to assess the influence of Valsalva leak point pressure (VLPP) on outcome of transobturator suburethral tape (TOT) implantation. MATERIAL AND METHODS: 65 female patients underwent surgery between March 2004 and November 2005. Their inclusion criterion was urodynamic stress urinary incontinence (SUI). The exclusion criteria were detrusor overactivity, detrusor underactivity, a significant post-void residuum and genital prolapse. "Subjective improvement" was considered as the difference between postoperative urinary-incontinence specific quality of life compered with its preoperative value (deltaIQoL=IQoL*-IQoL). RESULTS: Postoperative leakage and postoperative urinary incontinence specific quality of life in 1st versus 2nd group were 1.2+/-1.1 g and 90.6+/-5.1 versus 4.6+/-3.1 g and 84.0=5.6 respectively (p<0.005 and p<0.005 respectively). CONCLUSIONS: Cure and success rates were significantly higher in patients with higher VLPP values compared with patients with lower VLPP values. In spite of the fact that patients with higher VLPP values achieved significantly lower postoperative leakage, urine leakage decreased significantly more in patients with lower VLPP values. Patients with higher VLPP values reached significantly higher postoperative urinary incontinence-specific quality of life, however no significant difference was found in subjective improvement between patients with higher and lower VLPP values (Tab. 1, Ref. 23).

Retroperitoneoscopic approach in the treatment of symptomatic renal cysts.

INTRODUCTION AND OBJECTIVE: The authors present the results and follow up of patients with simple parenchymal and peripelvic cysts who underwent retroperitoneoscopic cyst decortication. MATERIAL AND METHODS: The records of 19 patients who underwent 3/4-port retroperitoneoscopic cyst decortication between January 1999 and January 2004 were retrospectively reviewed. All patients admitted to the hospital were symptomatic, the most common presenting syptoms were flank pain (19p) and hematuria (6p). The cyst size ranged from 8 to 15cm (mean size 10cm). 10 cysts were located on the right kidney and 9 cysts on the left kidney. The mean age of patients was 51 years. 16 patients had a simple parenchymal cyst corresponding to Bosniak type I (8 patients underwent cyst aspiration and sclerotherapy with 96 % alcohol in past), 2 patients had peripelvic cyst corresponding to Bosniak type II and 1 patient had a parenchymal cyst Bosniak type II. RESULTS: Retroperitoneoscopic renal cyst decortication was successfully performed in all patients, no conversion was needed. The mean operative time was 70 min (50-90 min) in patients with parenchymal and peripelvic cysts. The mean operative blood loss was 70 ml (50-130 ml) and the mean lenght of hospital stay was 3 days (2-5 days). The follow up ranged from 6 to 48 months and during that period were all patients asymptomatic, with no signs of recurrence. CONCLUSIONS: Retroperitoneoscopic cyst decortication is a safe and effective operative procedure in the treatment of symptomatic renal cysts with the minimal complication rate and excellent results (Tab. 2, Fig. 3, Ref. 30).

Epicystoscopic approach in the treatment of foreign body in the urethra and urinary bladder.

In most cases the foreign body can be removed transurethrally with a pair of grasping forceps. In some cases objects have to be cut or resected into small fragments, making it easier to extract the object or wash it out. An open surgical procedure via suprapubic transvesical approach is reserved for large-sized bodies or in cases when endoscopic methods are unsuccessful. The laparoscopic removal is one of further techniques that provide the opportunity to untie the knots (Fig. 6, Ref. 6).

The correlation of procalcitonin serum levels with the presence of biliary obstruction.

INTRODUCTION: There is still no general agreement as to which patients suffering from attacks of acute biliary pancreatitis should undergo emergent endoscopic retrograde cholangiopancreatography (ERCP) with subsequent endoscopic intervention (endoscopic papilotomy, stent placement etc.). Many authors have described large differences in Procalcitonin (PTC) serum levels in patients suffering from biliary pancreatitis as opposed to patients whose acute pancreatitis is based on toxic etiology. Therefore, we have investigated the correlation of Procalcitonin serum levels with the presence of biliary obstruction in patients undergoing ERCP examination. MATERIAL AND METHODS: From 1.8.2004 to 31.3.2005, 97 patients undergoing ERCP were enrolled into the study. Blood samples were taken from each patient just before their ERCP examinations, and PCT serum levels were subsequently correlated to ERCP findings. RESULTS: ERCP examinations were completed in 90 out of 97 patients. Bile ducts obstructions were confirmed in 61 out of 90 patients and the mean serum level of PTC was 0.078 ng/ml. In the remaining 29 patients ERCP revealed normal findings and the mean PCT value was 0.069 ng/ml. There was no statistical correlation between PCT serum levels and the presence of biliary obstruction on ERCP findings. CONCLUSION: The measurement of PCT serum levels is of no help in the identification of patients, who should undergo emergent ERCP due to acute biliary pancreatitis (Tab. 1, Fig. 1, Ref. 6).

The clinical value of the procalcitonin in prediction of severity and outcome in acute pancreatitis.

BACKGROUND/AIMS: Early identification of patients with severe forms of acute pancreatitis (AP) and subsequent management of these high risk patients are the most important aims in order to decrease mortality from AP. Procalcitonin (PCT) as a marker for systemic inflammation appears to be a useful marker for early identification of severe forms. METHODOLOGY: 101 patients with confirmed AP have been admitted to department of general surgery. PCT values were measured in each patient on admission and after 12 hours. PCT levels were correlated to the disease's course and prognosis. Results are given through PPV and NPV. Immunoluminometric assay (BRAHMS Diagnostica) was used for measurement. RESULTS: PPV and NPV for prediction of disease's course were better for PCT than for CRP PPV 64.7% versus 36% and NPV 82,6% versus 79.6% and for prediction of fatal outcome PCT reached 75% and 100% for cut off value 5 ng/ml. CONCLUSIONS: PCT seems to be a useful screening parameter for detecting severe AP and for identifying the patients who need ICU treatment, ATB covering and who can benefit from the novel therapies.

CEA and relapse after the operation of colorectal carcinoma.

BACKGROUND: Relapses have an important meaning in relation to the curative surgical intervention. In RO resections according to UICC classification, the local relapses were classified as the most important factor for survival. Without any doubts the most important of these tumor-biological prognostic factors in patients with colorectal carcinoma is the carcino-embryonal antigen. Up to now, the unquestionable importance of the determination of serum levels of CEA for the detection of relapses is most often described. MATERIAL AND METHODS: This study is retrospective, not randomized. Analyzed were medical records and data of patients, who underwent the surgery of colorectal carcinoma at IInd Department of Surgery, University Hospital, Faculty of Medicine, Comenius University, Bratislava, in period from January 1st, 1986 to December 31st, 1995. In our analysis we evaluate the age and gender of patients, date of the surgery and type of the surgery from the point of acuteness, as well as radicality, staging of the disease, levels of the serum CEA. Serum levels of carcino-embryonal antigen before operation were determined and evaluated. In patients, who remaind in the monitoring at our department we examine CEA in regular intervals. RESULTS: From our group of patients, in 28 patients the relapse of the disease was determined here. Before the first operation, the preoperative level of CEA was examined in 15 patients and in 13 patients it was not. From 15 patients with examined CEA level, 7 patients (46.7%) had increased and 9 patients (53.3%) normal level. In twenty-seven patients CEA level was examined to reveal a relapse. One patient was diagnosed during the acute surgery and CEA was not determined prior this operation. From the remaining 27 patients, CEA level was positive in 20 patients (74.1%) and 7 patients had normal levels (25.9%). From these 7 patients with normal CEA level, in 5 cases it was locoregional relapse and 2 patients have distant metastases. From all patients, in whom the relapse was determined at our department, in 13 patients locoregional relapse was detected and in 15 patients distant metastases were diagnosed. CONCLUSION: Due to the sensitivity of serum level of CEA for detection of relapses, which is higher compared to the primary tumor and also to found lead time 4 months we think the postoperative regular determination of CEA in patients after the curative resection is appropriate. Earlier determination of less progressive relapse is definitely important, although the current long-term survival after the surgery for relapses is not optimistic. Development of surgical procedures as well as alternative treatment can bring better results in less developed relapse of the disease. (Ref. 28.).

Renal autotransplantation in irreversible ureteral injury.

The authors describe a case of ureteral avulsion in ureteroscopy and extraction of calculus from the central part of the ureter. They chose a renal autotransplantation for the ureter reconstruction. They share the same opinion as the authors who use renal autotransplantation as the method of choice in irreversible ureteral injury. Ureteral avulsion is the most severe complication of ureteroscopy. The authors described a case of right ureteral avulsion, with subsequent autotransplantation as the final solution. (Fig. 6, Ref. 7.).

[Prevention of venous thromboembolism in general and laparoscopic surgery]. / Prevencia venózneho tromboembolizmu vo vseobecnej a laparoskopickej chirurgii.

Pulmonary embolism and thromboembolic attacks remain the most frequent cause of mortality in patients after general surgery or laparoscopy. The authors review the risk factors, indication of prophylaxis of thromboembolism and the currently used modes of prophylaxis. The so-called low-molecular-weight heparins (LMWH) are the most frequently used modes of prophylaxis. The algorithm of prevention and doses of LMWH used in general surgery and laparoscopy are presented. (Tab. 5, Ref. 17.)

[Reoperations after biliary-digestive system anastomosis]. / Reoperácie po biliodigestívnych anastomózach.

During the period from July 1997 to November 1999, five patients were electively surgically treated at the II Surgical Clinic due to stenosis of biliodigestive anastomoses. All patients were afflicted by stenosis of hepatojejunal anastomoses which were performed at various surgical clinics in order to correct iatrogenic lesions of biliary ducts. Re-operation was performed by use of the mucosa-to-mucosa anastomosis technique without transanastomotic drainage. There were two post-operational complications and no mortality. The authors discuss the safety and effectiveness of biliodigestive anastomoses carried out without transanastomotic drainage, and present the possibilities and indications of endoscopic therapy in these states.

[Preoperative levels of CEA and survival in patients with surgical treatment of colorectal carcinoma]. / Predoperacná hladina CEA a prezívanie pacientov operovaných na kolorektálny karcinóm.

From the 1st January 1986 until the 31st December 1995 397 patients were operated on at the IInd Surgical Clinic of Medical Faculty, Comenius University in Bratislava because of colorectal cancer. Of them 325 patients were operated on electively and 72 patients were operated on as emergency cases. The authors analysed average survival time and the relationship between survival and preoperative level of CEA. The average survival time, without dividing into stages was 37.3 months, not involving patients with perioperative lethality of 43.1 months. 5 years survival without dividing into stages was 36.8%. Average survival of patients without dividing into stages with increased preoperative level of CEA was 28.7 months, in patients without increased level of CEA it was 42.5 months. 5-years survival in patients with normal preoperative level of CEA was 60.5%, in patients with increased level of CEA it was 35.7%. There was highest difference when dividing to subgroups based upon the stage of the disease between groups with stage pT4N0M0 and pT1-4N1-3M0. The positiveness or negativeness of the preoperative level of CE supports the staging of disease and supposes a significant difference in 5-years survival in patients especially in the mentioned stages. Although this difference is obvious, it is not possible to suppose individual prognosis of patients and the necessity of an adjuvant therapy. (Tab. 2, Ref. 31.)

Effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril on endothelial and platelet functions in essential hypertension.

Endothelial damage and platelet hyperactivity may play a role in the vascular complications of essential hypertension. Restoration of endothelial function and reduction of increased platelet aggregation in essential hypertension are one of the aims of modern anti-hypertensive therapy. Therefore, the effect of angiotensin converting enzyme (ACE) inhibitors on endothelial and platelet functions is of interest. In the present study, 23 healthy normotensives and 23 age- and sex-matched patients with non-treated essential hypertension (1st and 2nd stage according to WHO) were investigated. Measurements of endothelial and platelet functions in hypertensives were carried out before therapy, after 1 week of placebo administration, after 1 week and after 1 month of perindopril therapy in a once daily dose of 4 mg. Plasma thrombomodulin (ELISA method) and beta-thromboglobulin (radio immunoassay method) were assayed and platelet aggregation (spontaneous and induced by adrenaline) was measured. The values of plasma thrombomodulin, a novel marker of endothelial function, were compared between age- and sex-matched normotensives and hypertensives. A significant decrease of adrenaline-induced platelet aggregation was observed after 1 month of perindopril therapy in comparison with the values before therapy or after 1 week of perindopril therapy ( P < 0.02 and P < 0.05 respectively). There were no significant changes in plasma thrombomodulin or beta-thromboglobulin following therapy. We failed to find significant changes of plasma thrombomodulin in patients in the early stages of hypertension, but its tendency to be higher than in normotensives does not rule out some vascular damage. The inhibitory effect of perindopril on platelet aggregation may be a further advantage of this drug. Since no changes were found after 1 week of therapy, the reduction of adrenaline-induced platelet aggregation after 1 month of therapy may be explained by an indirect effect of perindopril on platelet function, probably asa result of protective action on the arterial wall.