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Persistent postoperative dysphagia diminishes the good effect of laparoscopic anti-reflux surgery. An excessive increase of the intraoperative lower esophageal sphincter pressure (LESp) is supposed to be related to the persistent postoperative dysphagia and its knowledge could lead to the modification of the surgical technique followed by improved clinical outcomes. This study aims to describe the relation between the intraoperative LESp increase and the incidence of postoperative dysphagia and to find whether a combination of intraoperative manometry and mechanical calibration of the wrap is able to decrease the incidence of the persistent postoperative dysphagia.The randomized, prospective, two-branch study included 39 patients suffering from symptoms of gastroesophageal reflux disease. All patients underwent pre- and postoperative manometry, 24-hour pH-metry and laparoscopic anti-reflux surgery. The intraoperative LESp was measured in the study arm only.A higher incidence of persistent postoperative dysphagia was revealed in patients with the intraoperative LESp increase more than 15 mmHg. This complication was not found in patients with the LESp increase under 8 mmHg with no impact on the efficacy of the surgery. The combination of the intraoperative manometry and the mechanical calibration of the wrap seems to bring the benefit only to a small number of the patients.According to our results, the intraoperative LESp measurement proved to be a useful supplementary method which was easy to perform, and which enables a modification of the surgical technique to decrease the incidence of the persistent postoperative dysphagia.

Solid pseudopapillary tumor of pancreas belongs to rare tumors of exocrine pancreas, which typically affects young women. In a retrospective study the authors reviewed their experience obtained with five cases of this tumor from 1994 until the present time. The group included four women (from 16 to 47 years, mean age 25 years) and one man (43 years old). Clinical symptoms were characterized by abdominal pain in three cases, two years lasting domed belly and an incidental finding in another case. The palpation examination of epigastrium revealed a palpable tumor, visible in sonographic examination and CT. All patients underwent surgical resection of the tumor. The tumor affected cauda of the pancreas (pancreatic tail) in four cases and head of the pancreas in one case. Histopathological examination established the diagnosis of solid pseudopapillary tumor of pancreas in four cases and solid pseudopapillary carcinoma in one case. A typical immunophenotype of tumorous cells was demonstrated and in four cases there was positivity of progesterone receptor. The progesterone and estrogen receptors were negative in the male patient. Solid pseudopapillary tumor of pancreas is the tumor of low malignancy with excellent prognosis. Correct diagnosis and surgical removal of the tumor results in curing up in most cases.

Overexpression of p21WAF1/CIP1 was recently described as an early event in the development of pancreatic intraepithelial neoplasia. Since activating K-ras mutations are described in more than 80% of pancreatic cancers and are known to increase intracellular levels of p21WAF1/CIP1 in experimental models, the possible role of activating K-ras mutations in an induction of the p21WAF1/CIP1 expression was investigated in our study. We examined 71 surgical specimens, 29 of chronic pancreatitis and 42 of invasive ductal adenocarcinoma both having a large spectrum of PanIN (pancreatic intraepithelial neoplasia) lesions. Expression of p53 and p21WAF1/CIP1 was examined immunohistochemically and codon 12 K-ras mutational analysis was performed using the very sensitive mutant-enriched PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis. Our study demonstrated the overexpression of p21WAF1/CIP1 as an early event in the development of pancreatic intraepithelial neoplasia in the group of chronic pancreatitis and invasive adenocarcinoma as well. Overexpression of p21WAF1/CIP1 increased progressively from normal ducts through the spectrum of PanIN lesions to invasive carcinomas. The p53 overexpression increased again progressively according to the severity of the lesion and seems to be a later event in the development of pancreatic intraepithelial neoplasia if compared to p21WAF1/CIP1 expression. Our results confirmed also the possible p53 independent p21WAF1/CIP1 expression in some PanIN2, PanIN3 lesions and invasive carcinomas. K-ras mutations were not revealed in samples with only low grade PanIN lesions (PanIN1a and PanIN1b). K-ras mutations were detected in 69,4% adenocarcinomas and in only one case of chronic pancreatitis. Two codon 12 K-ras positive pancreatic carcinomas showed K-ras mutations in the surrounding normal pancreatic tissue. In adenocarcinomas, no statistically significant correlation was found between K-ras mutational status and p21WAF1/CIP1 and p53 expression, respectively. The possible role of activating K-ras mutations in an induction of p21WAF1/CIP1 expression was not confirmed in this study.

Overexpression of HER-2/neu was described in pancreatic intraepithelial neoplasia (PanIN) and in invasive ductal adenocarcinoma of pancreas in a variable proportion of cases. The effects of HER-2/neu overexpression on mitogenic signalling and cell cycle progression were studied in breast luminal epithelial cells and mitogen activated protein kinase-dependent induction of p21(WAF1/CIP1) was found to be necessary for G1 phase progression. Overexpression of p21(WAF1/CIP1) was described as an early event in the development of PanIN by Biankin et al. (2001) and this finding was supported by our previous study that, moreover, did not confirm the possible role of activating K-ras mutations in the induction of p21(WAF1/CIP1) overexpression. Relationship between p21(WAF1/CIP1) expression and HER-2/neu status in PanIN lesions and ductal adenocarcinoma of the pancreas was investigated in our study. Expression levels of p21(WAF1/CIP1) and HER-2/neu were examined imunohistochemically and the amplification of HER-2/neu gene was evaluated by fluorescence in situ hybridisation in HER-2/neu overexpressing adenocarcinomas. Fourty nine pancreatic resection specimens from patients with invasive adenocarcinoma were included into the study. A large spectrum of PanIN lesions adjacent to the structures of infiltrating adenocarcinoma was also examined. The possible role of HER-2/neu in an induction of p21(WAF1/CIP1) overexpression was not confirmed and p21(WAF1/CIP1) overexpression seems to be HER-2/neu independent in pancreatic ductal adenocarcinoma according to our results. Increasing levels of HER-2/neu expression were demonstrated in pancreatic intraepithelial neoplasia and in 18.75% of pancreatic adenocarcinoma. The only 2 from 9 HER-2/neu overexpressing adenocarcinomas showed the amplification of HER-2/neu gene. Based on these results, the overexpression of HER-2/neu in pancreatic adenocarcinoma seems to be a result of increased transcription rather than gene amplification. Therefore HER-2/neu represents a good target for therapy of pancreatic adenocarcinoma only in isolated cases.

Complex diagnosis of muscular dystrophies including clinical, bioptical and molecular genetic approaches has been provided in a limited extent in this country. Our group of neurologists, pathologists and geneticists has examined approximately 240 patients suspected of having muscular dystrophies, mostly coming from Southern and Northern Moravia. The patients were sent to the examination most often from departments of neurology and clinical genetics, and less frequently from departments of internal medicine. According to the final diagnosis, the patients were divided into groups: with dystrophinopathies and carriers of dystrophinopathies (DMD/BMD), merosin deficient form of congenital muscular dystrophy, and Emery-Dreifuss muscular dystrophy including the carriers of this disease. Some relatives of patients with dystrophinopathies were also examined using the methods of segregation analysis. High proportion of the DMD/BMD patients can be detected by the methods of molecular genetics. Analysis of mRNA using RT PCR and PTT enables the detection of deletions, duplications, and point mutations in dystrophin gene and encompasses a larger diagnostic scope in comparison with examinations of DNA level by the multiplex PCR method from the peripheral blood which enables only deletion detections. Immunophenotyping of the dystrophin protein plays an important role especially using antibodies against carboxyterminal (DYS2) and rod domain (DYS1) of dystrophin. Deficient sarcolemmal expression of DYS2 and DYS1 reveals unambiguously a pathological dystrophin. On the other hand, less pronounced deficiencies in dystrophin expression in BMD patients and DMD/BMD carriers may not always be detected in muscle biopsies. In this case, it is necessary to supplement the examination by Western blotting and genotype analysis. The examination of patients with clinically diagnosed muscular dystrophy should start with a muscle biopsy which enables the estimation of presence and degree of structural changes. Application of antibodies against the components of DGC and emerin may reveal a deficiency in expression of these proteins. Immunohistochemical examination completed by Western blotting leads to the subsequent molecular genetic analysis of DNA or mRNA. Secondary deficiencies in expression of other DGC proteins are often revealed in muscle biopsies of dystrophinopathies and this fact must be taken into account in the evaluation of immunohistochemical findings. There is a possibility of replacement of invasive muscle biopsy by skin biopsy or buccal mucosal smears in cases of merosin and emerin deficiencies. Commercially available antibodies against merosin, emerin, calpain and sarcoglycans enable extensive identification and detailed classification of muscular dystrophies. Screening of the patients based on the application of methods described and discussed in this report is the task of the forthcoming period.