Downregulation of miR-30c-5p expression in colorectal cancer tissue is sex-dependent.

We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor beta (ERbeta) mRNA levels in tumor was tested. In males with low expression of ERbeta, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERbeta mRNA levels and in females. Accordingly, males with low expression of ERbeta and high expression of miR-30c showed a better survival that those with low expression ERbeta and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERbeta mRNA in tumor tissue.

Sex-dependent regulation of estrogen receptor beta in human colorectal cancer tissue and its relationship with clock genes and VEGF-A expression.

The incidence of colorectal cancer (CRC) shows a sex-dependent difference in humans. The aim of this study was to analyze estrogen receptor beta mRNA (ERbeta) expression in patients with CRC with respect to their gender and clinicopathological features. Since cancer progression is accompanied by tumor vascularization, VEGF-A (vascular endothelial growth factor A) transcription was analyzed along with ERbeta mRNA. ERbeta mRNA was also correlated with the expression of clock genes, which are known to influence the cell cycle. ERbeta mRNA expression in females with CRC showed an inverse association with increasing tumor staging that was not observed in males. Lower levels of ERbeta mRNA were observed in females with a higher clinical stage compared with those with earlier-stage tumors. ERbeta mRNA expression showed a significant positive correlation with mRNA of clock genes period 2 and cryptochrome 2 in healthy but not in cancerous tissue in males. Expression of VEGF-A mRNA showed a negative correlation with ERbeta mRNA after splitting of the cohort according to gender and nodus involvement. We propose that gender differences in ERbeta mRNA expression in tumors during the early stages of CRC can partially explain the lower occurrence of CRC in females compared with males.

The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor adjacent tissues correlates differently dependent on tumor location.

Colorectal cancer (CRC) exhibits differences in its features depending on the location of the tumor. The role of the circadian system in carcinogenesis is accepted, and many studies report different clock gene expression in tumors compared to healthy tissue. However, little attention is given to the changes in clock genes in tumors arising from various locations across the colon and rectum. The aim of our study was to investigate the expression of the clock genes cry1 and cry2 in human CRC tissue and tissue adjacent to colorectal tumors in a cohort of 64 patients by real time PCR. Expression of cry1 in the entire patient cohort was higher in tumors compared to adjacent tissues in the right-sided colon but not in the left-sided colorectum. Difference in cry1 expression between tumor and adjacent tissue in the right-sided colon was preserved in women and a trend was observed in men. Higher expression of cry1 in the right-sided colon tumor tissue was associated with worse survival in women and the expression of cry1 in the left-sided colorectum was significantly higher in the adjacent tissue compared to tumor in men but not in women. Expression of cry2 was lower in the tumor than in adjacent tissue in both the right and left-sided colorectum. This trend was generally preserved, but the difference reached significance level only in the male left-sided colon, and cry2 expression in the tumor tissue significantly correlated with location of the tumor in men with grade 2 cancer. Finally, we detected significant correlation between tumor location and cry1 expression in the adjacent tissue and the combined results establish that tumor influence on adjacent tissue is dependent on tumor location. Changed clock gene expression should therefore be considered in specific CRC patient sub-groups.

Gender-dependent expression of leading and passenger strand of miR-21 and miR-16 in human colorectal cancer and adjacent colonic tissues.

miRNAs are small regulatory RNA molecules involved in posttranscriptional gene silencing. Their biosynthesis results in the formation of duplex consisting of a leading and a passenger strand of mature miRNA. The leading strand exhibits the main activity but recent findings indicate a certain role of the passenger strand as well. Deregulated levels of miRNA were found in many types of cancers including colorectal cancer. miR-21 and miR-16 were indicated as possible markers of colorectal cancer, however, small attention to gender differences in their expression was paid so far. Therefore, the aim of our study was to investigate the expression of miR-21-5p, miR-21-3p, miR-16-5p and miR-16-3p in human colorectal cancer tissue and compare it to the adjacent tissues taken during surgery in men and women separately. Our results showed an up-regulation of all measured miRNAs in tumor tissue compared to adjacent tissues. As expected, tumors and adjacent tissues exhibited a significantly higher expression of leading miRNAs compared to passenger strand of miR-21 and miR-16. The expression of leading and passenger strand of miR-21 and miR-16 positively correlated exhibiting the highest correlation coefficient in the distal tissue. The expression pattern showed gender-dependent differences, with higher levels of miRNA in men than in women. Our findings indicate a gender-related expression pattern of miRNA, which should be considered as an important factor in generating new prognostic or diagnostic biomarkers.

Primary hyperparathyreosis: is concordant sonography and scintigraphy really so important?

BACKGROUND: In primary hyperparathyreosis, US and scintigraphy are the most usual preoperative localization methods for detection of parathyroid adenomas or hyperplasia. RESULTS: 88 (80 female) patients were detected. Unilateral neck exploration was performed in 43 patients (48.9 %) and bilateral exploration in 45 patients (51.1 %). The cure rate was 97.6 %. None case of parathyroid hyperplasia was detected, there were 2 cases of duplex adenoma. For left/right and quadrant localization, sensitivity of US was 71.05 % and 55.07 %, of scintigraphy 95.77 % and 88.71 %, and in concordant imaging 97.67 % and 96.77 %. Analogically, PPV was: US 91.53 % and 76.00 %, scintigraphy 87.18 % and 74.32 %, concordant imaging 93.33 %and 81.08 %. Only US sensitivity was significantly lower, all other differences showed no statistical significance. CONCLUSION: Our data showed low sensitivity but a high positive predictive value of ultrasonography and a high diagnostic value of scintigraphy. Sensitivity and the positive predictive value of concordant localization showed no significant difference, compared to scintigraphy. The routine need for concordance for parathyroid adenoma localization appears dubious, however, its value for prediction of multiglandular disease remains important for protocols that do not apply peroperative localization (Tab. 2, Ref. 35).

Rare conditions of gastrointestinal bleeding.

The aim of this paper is to analyze and discuss an infrequent topic, i. e. rare conditions of gastrointestinal bleeding.Bleeding from gastrointestinal system is a common cause of acute abdomen and the most frequent causes are generally known.Clinicians, first of all emergency medicine staff, surgeons and internists (gastroenterology specialists), general practitioners, or less frequently other specialists, sometimes meet with less common causes of acute or chronic bleeding from gastrointestinal organs. It is quite important to be aware of the possibility the bleeding being caused by some rare condition, which is not so often met in medical practice, because of their great diagnostic and therapeutic problem. The low index of expectation of such a rare etiological unit could be the reason why destiny of such patients can be extremely problematic and why clinicians may fail at management of these patients (Fig. 4, Ref. 8).

[Changes in membrane enzymes in warm liver ischemia]. / Zmeny membránových enzýmov pri teplej ischémii pecene.

BACKGROUND: The aim of the study is to perform a morphological analysis of certain membrane enzymes and parenchymal alterations during warm ischemia in the pig liver. METHODOLOGY: Standard hepatectomies were performed in a set of 24 pigs. Intraoperative intravenous (portal vein) hydroxyl radical scavenger Stobadine and Pentoxifylline was administered. Tissue specimens were removed from the margo acutum in interval 10, 60, 80 et 100 minutes. Applied methods of morphological analysis were concentrated on studying the activity of enzymes, which are regarded as cell membrane condition markers. First of them was the alkaline phosphatase, the second studied enzyme was the 5'-mononucleotidase. Detected findings in control group were compared to other two groups. We evaluated each sample using Image Forge Version 1.1 software (PROVER LTD., Bratislava). Applying this software we measured percentage of pre-measured activity levels of both enzymes. RESULTS: In normal pig liver, the activity of alkaline phosphatase was regularly distributed in sinusoid walls in the whole lobule. At 10 minutes after the beginning of the warm ischemia, we have found focal losses of enzyme activity, especially in cells of zone 3 of the liver lobuli. One hour after the beginning of warm ischemia were the local losses of enzyme activity even more pronounced. Decreased bile canalicular 5'-mononucleotidase activity reflects cell damage, especially in pericentral areas after 60 min.of ischemia and a further decrease in activity at all surfaces of the membrane. Total amount of enzyme activity is different. CONCLUSIONS: Morhological findings of enzyme activities showed that zone 2 and 3 of the liver lobule are essential for the organ survival. The study showed, that intravenous administration of Pentoxifylline and Stobadine probably protects the liver from warm ischemia injury.

Noncolonic cancer stem cells in bone marrow of colorectal cancer patients.

OBJECTIVE: To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates. METHOD: Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 x 10(6) BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single-strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI-positive patients were isolated with immunobeads coated with magnetically labelled anti-human epithelial antigen antibody and DNA-screened for mutations. RESULTS: Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow-up. Twenty-five (2-170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty-two patients developed LM at 36-month follow-up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer-specific death rates, or all death rates. CONCLUSIONS: Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates.

Warm liver ischemia in experiment and lysosomal markers.

BACKGROUND: The aim of the study is to perform a morphological analysis of certain lysosomal enzymes and parenchymal alterations during warm ischemia in the pig liver. METHODS: Standard hepatectomies were performed in a set of 24 pigs. Intra-operative intravenous (portal vein) Pentoxiphylline and hydroxyl radical scavenger Stobadine was administered. Tissue specimens were removed from the margo acutum in 10 minutes interval. RESULT: In normal pig liver, the acid phosphatase (ACP) activity is in not numerous Kupffer cells and on the biliary pole of hepatocytes, diffusely in the whole parenchyma. One hour after the beginning of warm ischemia, there was an increase in ACP activity in the cytoplasm of hepatocytes. The activity in Kupffer cells could not be detected. Lactate dehydrogenase (LDH) is localized exclusively in the cytoplasmic matrix of liver cells, so only cytoplasmic enzymes leak into the blood plasma. LDH activity has remained low in areas around portal and central veins. CONCLUSION: Morphological findings of enzyme activities showed that zone 2 and 3 of the liver lobule are essential for the organ survival and signs of diffusion of lysosomal enzymes into the cytoplasm of hepatocytes indicate one of the possible explanations for the findings after liver reperfusion. The study showed that intravenous administration of Pentoxiphylline and Stobadine protects the liver from warm ischemia injury (Tab. 2, Fig. 2, Ref. 37). Full Text (Free, PDF) www.bmj.sk.

Beneficial effects of intravenously administered N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a prospective randomized study.

BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting operation (CABG). Experimental data have shown antiarrhythmic effects of n-3 polyunsaturated fatty acids (PUFA) on myocardial cells. Orally administered PUFA could significantly reduce the rate of postoperative AF. We assessed the efficacy of PUFA for the prevention of AF after CABG. PUFA were given intravenously to prevent variation in bioavailability. METHODS AND RESULTS: 52 patients were randomized to the interventional group, 50 served as controls. In the control group free fatty acids (100 mg soya oil/kg body weight/day) were infused via perfusion pump, starting on admission to hospital and ending at discharge from intensive care. In the interventional group PUFA were given at a dosage of 100 mg fish oil/kg body weight/day. Primary end point was the postoperative development of AF, documented by surface ECG. Secondary end point was the length of stay in the ICU. The demographic, clinical and surgical characteristics of the patients in the two groups were similar. Postoperative AF occurred in 15 patients (30.6 %) in the control and in 9 (17.3 %) in the PUFA group ( P < 0.05). After CABG, the PUFA patients had to be treated in the ICU for a shorter time than the control patients. No adverse effects were observed. CONCLUSIONS: Perioperative intravenous infusion of PUFA reduces the incidence of AF after CABG and leads to a shorter stay in the ICU and in hospital. Our data suggest that perioperative intravenous infusion of PUFA should be recommended for patients undergoing CABG.

The effects of occlusive techniques on the short-term prognosis after liver resections.

BACKGROUND/AIMS: Anatomic liver resection can be performed without vascular occlusion, but controlling blood loss during liver parenchyma dissection by compression or clamping of vessels in the liver hilus is almost the rule. The aim of this study is to assess the negative consequences of different types of occlusion techniques used during liver parenchyma dissection. METHODOLOGY: From 2001 to 2003, 43 anatomical liver resections were performed in patients with primary and metastatic tumors. Patients were divided into three groups according to the duration and the type of occlusion of incoming blood vessels in the hepatoduodenal ligament (continuous over 20 min, continuous under 20 min, or interrupted blood-vessel occlusion for 5 min after every 20 min of occlusion). Blood level of bilirubin, ALT, AST and prothrombin time were evaluated in the postoperative period. RESULTS: Within the continuous occlusion group that lasted longer than 20 minutes (37 +/- 14 min) increase in levels of bilirubin and liver enzymes and decrease of prothrombin time were noted as compared to the group with occlusion shorter than 20 minutes and to the group with intermittent occlusion over 20 minutes (34 +/- 5 min). CONCLUSIONS: From results issued, it can be seen that using intermittent occlusion during liver parenchyma dissection lasting longer than 20 minutes causes less ischemic-reperfusion injury in the remaining liver parenchyma than by using continual occlusion.

The abdominal compartment syndrome.

The abdominal compartment syndrome has received considerable attention only recently. It may be defined as adverse physiologic consequences that occur as a result of an acute increase in the intraabdominal pressure. The most common causes of ACS are haemorrhage, visceral oedema, pancreatitis, bowel distension, venous mesenterial obstruction, abdominal packs, tense ascites, peritonitis, tumor. The mostly affected organ systems include cardiovascular, pulmonary, renal, central nervous and splanchnic. The diagnosis depends on the recognition of the clinical syndrome followed by an objective measurement of intraabdominal pressure, preferably that of the urinary bladder. The treatment consists of adequate fluid resuscitation and surgical decompression when necessary. (Tab. 1, Ref. 29.).

[The "open abdomen" as one of the possible therapeutic alternatives in postoperative complications]. / "Open abdomen" jedna z mozných liecebných alternatív pooperacných komplikácií.

The authors discuss the important problem of healing, infection of surgical wounds and causes of healing per secundam. Despite efforts on the part of surgeons to close the surgical wound, in particular in old people with polymorbidity, hypoproteinaemia and anaemia, disintegration of the surgical wound may occur which cannot be closed and healing must proceed while the abdomen is open.

[Surgical treatment of acute diverticulitis of the large intestine]. / Chirurgická liecba akútnej divertikulitídy hrubého creva.

The authors analyze in this paper covering a ten-year period (1990-1999) a group of patients with acute perforated diverticulitis. The patients were classified according to Hinchey's classification. During this period 35 patients were operated with a high preoperative morbidity. With regard to the low number of complications of acute diverticulitis the authors do not prefer early preventive resections of non-complicated diverticulitis, but they tend to extend indications, first of all in cases of repeated recurrences, haemorrhage and in case of stenosis. In the IIIrd and IVth stage according to Hinchey's classification dominates Hartmann's operative procedure. But the authors agree with the trend to perform resection with primary anastomosis in the IIIrd stage, especially in cases of a good status of the patient and short duration of the disease. In cases of acute perforated diverticulitis operated in the first 24-hour interval the mortality rate was 23.1%.

[Gastroduodenal hemorrhage]. / Súcasná problematika krvácania z gastroduodena.

Haemorrhage is a serious complication of peptic ulcer disease. It is an indication for urgent diagnostic and therapeutic endoscopy, which is at present the method of first choice. All patients with gastroduodenal peptic ulcer bleeding, who underwent endoscopy in Ist Department of Surgery in Bratislava between January 1995 and December 1999, were considered for retrospective study. A total of 291 patients (195 male and 96 female) underwent urgent endoscopy with a finding in 34.7% of patients with gastric ulcer and in 65.3% patients duodenal ulcer. The finding was Forrest I in 23%, Forrest II in 25.7% and Forrest III in 51.3% patients. Endoscopic hemostasis was used in 12.37% of patients. A first haemorrhage was found in 82.9% patients, a recurrent one in 17.1% patients. 41.5% of patients had positive peptic ulcer history. Surgical treatment was indicated in cases, when bleeding was not controlled by endoscopic means, or in cases of recurrent bleeding within 48 hours in 19 patients (6.52%).

[Compression therapy of leg ulcers]. / Kompresívna liecba vredov predkolenia.

The authors present a group of 76 patients with chronic venous insufficiency in the stage or crural ulceration. After staging of the disease (C 6, E prim, E sec, A sup. pr. ref., P re) in the first stage they used a conservative approach, the method of compressive bandages: either an elastic bandage or zinc-glue bandage (Varolast). 49 patients were cured by conservative treatment (64.5%) in the course of 5 months. 12 patients were indicated for surgery (15.8%). Thus the authors cured finally 80.2% patients. A relapse was recorded in 6 patients (7.8%) and in 9 patients treatment failed (11.8%). For treatment with zinc-glue bandages they recommend patients without obstruction in the deep venous system, with large chronic ulcers and associated oedema of the whole leg.

[Laparoscopic vagotomy in the treatment of recurrent duodenal ulcer]. / Laparoskopická vagotómia v liecbe recidivujúceho ulkusu duodéna.

The paper represents our results of laparoscopic vagotomies. In 1993 was the first successful laparoscopic vagotomy in Slovakia performed, at the 1st Department of Surgery, Faculty Hospital, Bratislava. From this time 10 operations with front superselective and dorsal truncal vagotomy were performed. Effectiveness of vagotomy was controlled after 12 months by examination of the gastric acidity. Decrease of gastric acidity in average above 61% was reached. Laparoscopic vagotomy, despite dominant conservative treatment of peptic ulcer, is the method of choice, if the conservative treatment is unsuccessful. (Fig. 3, Ref. 6.)

Melatonin content in plasma and large intestine of patients with colorectal carcinoma before and after surgery.

The distinct melatonin rhythm with higher concentrations during the darktime was found in plasma of both control patients and patients with colorectal carcinoma. Moderate surgery did not induce any changes in plasma melatonin levels, but a pronounced increase in both the day- and nighttime melatonin concentrations was found after surgical treatment for colon cancer. The melatonin content in the tumor tissue did not differ from that in the proximal and the distal parts of the resected gut, which were without signs of malignant changes. Neither concentrations of serotonin nor 5-hydroxyindole acetic acid differed among analyzed parts of the gut. Daytime melatonin concentrations in gut tissue (314.7 +/- 87.8 pg/g of wet tissue) were more than ten times higher than the daytime levels in circulation. It was hypothesized that increased levels of this hormone in the gastrointestinal tract may play an important protective role against the development of colorectal cancer via stimulation of the immune system, protection against free radicals, and interaction with fatty acid uptake and metabolism.

[Occurrence of tumors of the small intestine]. / Výskyt nádorov tenkého creva.

The authors present in this article the occurrence of the tumors of small intestine in the group of patients operated on at the Ist Department of Surgery, Teaching Hospital of Commenius University in Bratislava in the years 1957-1997. During this period 39 primary tumors of small intestine were registered, 29 of them being malignant. Histologically, the most frequent malignant lesion was adenocarcinoma, and the most frequent benign lesion adenomatous polyp. The highest frequency of occurrence of tumors of small intestine was in the 6th and the 7th decennium. (Tab. 4, Ref. 11.)

[Laparostomy in the treatment of severe intra-abdominal infections]. / Laparostómia v liecbe závaznej vnútrobrusnej infekcie.

The objective of the work was to evaluate the results of comprehensive treatment of protracted primary and secondary intraabdominal infection. Retrospective analysis of a group of patients in 1994-1998 using laparostomy, peritoneal lavage, thorough repeated cleansing of the peritoneal cavity, microbiological monitoring with subsequent aimed antibiosis and comprehensive intensive care provide evidence of the rescue of almost 40% liminally curable patients. The results justify the use of comprehensive therapeutic procedures in late stages of serious peritonitis.