Use of double-layer autologous dermal flap in the treatment of recurrent and/or infected incisional hernias: presentation of the surgical technique and the results of 1-year follow-up-a prospective, consecutive cohort study.

INTRODUCTION: The difficulties of treating recurrent and/or infected incisional hernias are well known in surgical practice. Several surgical techniques and various types of grafts are available for surgeons. This study presents a new surgical technique option together with the results of the 1-year follow-up. PURPOSE: The primary aim of the study is to present the surgical technique of the procedure suitable for the treatment of recurrent and/or infected incisional hernias. The secondary aim is to determine the recurrence rate and analyse the surgical complications. The tertiary aim is to present the quality of life test results performed 3, 6 and 12 months after the surgery. PATIENTS AND METHOD: The authors evaluated the results of 36 recurrent and/or infected incisional hernia surgeries (11 men, average age 60.6 years; 25 women, average age 58.9 years) performed with their own surgical method in the framework of a tightly controlled, prospective, interventional and observational consecutive cohort study conducted between 1 January 2011 and 31 December 2013 at a university surgical department. The study evaluates the results of the 1-year follow-up period. All 36 patients had at least one recurrence of abdominal wall hernia; 12 of them also had concurrent infection of the synthetic graft and a complicating fistula. The mean BMI was 31.82 kg/m(2) (25.2-43.5 kg/m(2)). The average size of the abdominal wall defect was 145.9 cm(2) (59-275 cm(2)). The abdominal wall reconstruction was performed using an autologous, double-layer dermal flap. The grafts, which had been inserted during previous surgeries, were removed completely. The autologous dermal tissue was prepared using the flap harvested during dermolipectomy. The reconstruction was achieved using a tension-free technique. The essence of the abdominal wall reconstruction is the completion of the abdominal wall defect by a double-layer autologous dermal flap. The original abdominal wall defect was not closed by direct sutures. The quality of the prepared dermal flap was histologically evaluated. IAPMS (intra-abdominal pressure monitoring set) was applied to verify intra-abdominal pressure in the post-operative period. The result of the surgeries was assessed using a quality of life questionnaire. RESULTS: No recurrence of the abdominal wall hernia was registered during the 1-year follow-up period. Abdominal bulking was observed in case of three patients (8.3 %). Wound infection occurred in one patient (2.77 %) and skin dehiscence in two patients (5.55 %). Haematoma was registered in case of one patient (2.77 %) on the fifth post-operative day. Seroma formation occurred in case of eight patients (22.22 %), which required percutaneous tapping. A fistula formation was observed in one patient (2.77 %) 45 days after the surgery. The intra-abdominal pressure remained moderately elevated during the early post-operative period (9.65-5.76 mmHg on post-operative days 1 and 5). Reoperation was performed in one case due to haematoma. No fatality occurred. CONCLUSIONS: The 1-year recurrence rate in case of the abdominal wall reconstruction using double-layer autologous dermal flap is favourable. Being compliant with the surgical technique developed, the procedure is safe to perform. The number of surgical site infections and fistula formations is low. Based on the questionnaires evaluated, all patients would choose this method instead of the previous reconstruction(s). The method is cost-effective. Based on the results, this procedure is feasible for the treatment of recurrent and/or infected abdominal wall, incisional ventral hernias in obese "high risk" patients.

Serum C-reactive protein and white blood cell level as markers of successful percutaneous drainage of acute sterile peripancreatic fluid collection.

BACKGROUND: Percutaneous drainage is not a widely used therapeutic method recently for evacuating peripancreatic sterile fluid collections in patients with severe acute pancreatitis.However, many clinical studies have proved its positive effects. AIM: We tested the changes in serum laboratory parameters:C-reactive protein (CRP), complement factor 3-4 (C 3-4),tumor necrosis factor a (TNF-a), amylase, lipase and white blood cell (WBC) count in patients treated by percutaneous drainage. PATIENTS AND METHODS: 10 patients with severe acute pancreatitis with peripancreatic fluid collection were monitored.Laboratory parameters and the amount of drained fluid were measured on the 1st, 5th and 10th day. Statistical analysis was performed by using Statistica for Windows (Version 7.0)software. P values less than 0.05 were considered statistically significant. RESULTS: We found significant positive correlation between the CRP and WBC serum level and volumes of the drained fluid. We used these parameters as markers of successful percutaneous drainage in case of patients with severe acute pancreatitis complicated with sterile peripancreatic fluid.There was no significant change in the levels of C 3-4,tumor necrosis factor-Î+-, amylase and lipase. CONCLUSIONS: Monitoring of serum CRP and WBC levels maybe recommended for follow up after percutaneous drainage of peripancreatic fluid. ABBREVIATIONS: CRP: C-reactive Protein TNFÎ+-: Tumour Necrosis Factor a, C3-4: Complement 3-4 WBC: White Blood Cell CT: Computed Tomography.

MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations.

INTRODUCTION: Hereditary Non-Polyposis Colorectal Cancer is an inherited disease with deleterious germline mutations in the DNA mismatch repair genes causing the development of colon cancer and other malignancies. This is the first study in Hungary screening the population of our colorectal cancer patients in order to identify the prevalence of the disease. METHODS: In families who met the Modified Amsterdam and Bethesda Criteria the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis. Those cases which showed high microsatellite instability underwent DNA sequencing and multiple ligation dependent probe amplification. RESULTS: Of the 1576 patients with colorectal cancer underwent screening for the modified Amsterdam and Bethesda criteria, 69 (4.4%) and 166 (10.5%) fulfilled the criteria respectively. 15 patients (31%) of the Amsterdam positive group and 19 patients from the Bethesda positive (18.1%) were MSI-H. There were 8 pathogenic mutations identified in 9 families (60%) in the Amsterdam positive group. 5 mutations were found in 5 families (26%) in the Bethesda positive group. 12 pathogenic mutations were identified, two of these are newly identified, and being published first in this work. These two new mutations were located on MLH1 (g.31276_35231del) and MSH2 (c.969_970delTC) genes. CONCLUSION: The prevalence of the mutations in the MLH1 and MSH2 genes was almost equal in our Hungarian colorectal cancer patients. One mutation in the MLH1 gene (c.143A > C; p.Q48P) was identified in three different families. Whether this mutation is the most frequent in the Hungarian population is still unidentified and warrant further investigation.

The value of 18-FDG PET/CT in early-stage breast cancer compared to traditional diagnostic modalities with an emphasis on changes in disease stage designation and treatment plan.

BACKGROUND: Proper preoperative staging is vital in the treatment of breast cancer patients. The aim of our study was to assess the value of the diagnostic information provided by PET/CT in surgical practice in breast cancer cases considered early-stage by conventional diagnostic modalities. METHODS: Whole-body 18-FDG PET/CT was performed on 115 breast cancer patients in whom traditional diagnostic modalities showed no signs of distant metastases or extensive axillary and/or extra-axillary lymphatic spreading, and the size of the primary tumor was <4 cm. RESULTS: The sensitivity of PET/CT in the detection of the primary tumor was 93%. The sensitivity of the traditional diagnostic modalities in the detection of multifocality was 43.8% while that of PET/CT was 100% (p < 0.001). In the assessment of axillary lymph nodes, ultrasound had a sensitivity of 30% and a specificity of 95%. The corresponding estimates for PET/CT were 72% and 96%, respectively. PET/CT detected distant metastases in 8 patients. TNM classification was modified after PET/CT scanning in 54 patients (47%). PET/CT data changed the treatment plan established upon the results of traditional imaging modalities in 18 patients (15.6%). CONCLUSIONS: PET/CT is able to assess primary tumor size and axillary lymphatic status more accurately than traditional diagnostic methods. It can detect distant metastases in 7-8% of those patients who were declared free of metastasis by clinical investigations. PET/CT scan modifies the disease stage determined by traditional diagnostic modalities in almost half of the patients and leads to a change in the treatment plan in every 6th patient.

A new mutation in Muir-Torre syndrome associated with familiar transmission of different gastrointestinal adenocarcinomas.

Hereditary Nonpolyposis Colorectal Carcinoma (HNPCC) is the most frequent inherited disease which can lead to the development of tumors in the colon and other locations. Its genetic basis is related to the germline mutation of the Mismatch Repair (MMR) genes. Muir-Torre syndrome is considered one of the subtypes of this disease, in which the HNPCC tumor spectrum is frequently associated with sebaceous carcinoma of the skin or keratoacanthoma. A 57 years old male patient is presented with a mucinous carcinoma of the caecum and an adenocarcinoma of the pancreas head. A malignant sebaceous carcinoma was removed from his left neck area. His family history was significant for two cases of colon carcinoma, two cases of stomach cancer and a case of metacron endometrial and skin tumor as well. Both the colon carcinoma and the skin tumor proved to be microsatellite unstable. An Arg>Pro switch missense mutation was found in codon 265 of the hMLH1 gene. This error was found in 4 other members of his family. The detected genetic alteration was considered pathogenic and was not published yet in English literature. The significance of this particular case is the rare tumor association in a patient with Muir-Torre syndrome (MTS). In cases of sebaceous skin lesions, evaluation of family history is of utmost importance in the early detection of HNPCC and in the follow up care of family members with the particular mutation.

Difficulties in recognizing families with Hereditary Non-polyposis Colorectal Carcinoma. Presentation of 4 families with proven mutation.

INTRODUCTION: Hereditary Non-polyposis Colorectal Carcinoma is the most frequent genetic disease leading to colon and other malignancies. Recognizing the condition requires extensive family history going back several generations focusing particularly on the types of tumors occurring in the family at different age groups. METHODS: In families who met the Amsterdam and Bethesda Criteria, the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis. Subsequently DNA sequencing was performed to detect an underlying Mismatch Repair Gene mutation and multiple ligation dependent probe amplification was applied for recognizing large deletions in Mismatch Repair Genes. RESULTS: In the investigated families 3 pathogen mutations, 1 large deletion and 2 cases of polymorphism were found. There is considerable difference between the families in terms of the types of malignancies and the age in which those appeared. CONCLUSION: Recognizing families with Hereditary Non-polyposis Colorectal Carcinoma presents great difficulties because of the variety of phenotypes in presentation. Special attention should be paid to small families and those who present with cancer of other than colon origin. Practicing physicians should be made aware of the fact that this disease may have atypical presentations. Follow up of families who have already been screened may be difficult for social, economical or religious reasons.

Surgical treatment of morbid obesity.

Morbid obesity is a multifactorial disease with great importance because of its life threatening associated co-morbidities. Its treatment has many different aspects and needs multidisciplinary collaborations. The most powerful way of treatment is the surgical intervention, which demands thorough preoperative investigations and patient selection. The bariatric surgical procedures went through significant development and many of them have only historical importance. The different interventions can be classified into mal-absorptive, restrictive and combined subgroups. In Europe the laparoscopic adjustable gastric banding seems to be the most widely applied procedure, which is purely a restrictive intervention. Apart from the low rate of complications it has many advantages, which fact was not characteristic to the formerly used procedures. These include: minimal aggressivity, reversibility, preservation of the gastrointestinal anatomy, adaptability for demands of care.

[New technique for surgical treatment of enterovaginal fistula]. / Enterovaginális sipoly kezelése mucous fistulával.

Enterovaginal fistulas most frequently occur following abdominal tumors, inflammatory bowel disease and radiation therapy. There is a tendency for spontaneous closure, although a surgical intervention is necessary in more than 50% of the cases. Mortality is between 15-25%. The quality of life is significantly worsened by an enterovaginal fistula of a patient already suffering from a malignant disease. To relieve the patient from her distressing situation a mucous fistula was constructed by exclusion of the small bowel loop participating in the formation of the fistula track. Bowel continuity was restored by anastomosis. The patient's quality of life improved significantly. This operation was performed in three cases without complications. We recommend this procedure as an alternative technique to improve our patients' quality of life.

[The importance of recognizing hereditary non-polyposis colonic carcinoma]. / A herediter nonpolyposis colon carcinoma felismerésének gyakorlati jelentósége.

The clinical diagnosis of hereditary nonpolyposis colon carcinoma (HNPCC) can be made in more than 5% of all colorectal cancer cases, depending on the stringency of criteria used. The disease is inherited in an autosomal dominant fashion but penetrance is lower than 100%. The diagnosis must be verified by the demonstration of germline mutations of DNA "mismatch repair" genes. Although yet an exception in our national health practice, these tests are routinely applied in some centers abroad. The recognition of the syndrome is important since these patients can enter a surveillance program and may be cured. The most important pertaining information is summarized through the demonstration of our own case.

Integrin expression on normal and neoplastic human breast epithelium.

Integrin adhesion receptor expression of different benign and malignant breast tumours was examined by means of immunohistochemical techniques. A panel of seven different anti-alpha and two different anti-beta subunit antibodies was used. Normal breast epithelium displayed a well characterized and constant pattern of integrin expression consisting of strong alpha 1,2,3,6 and alpha v, and a relatively weaker beta 1 and beta 3 staining. No staining for alpha 4 or alpha 5 could be detected on the epithelial cells. Benign fibroadenomas did not show changes in their receptor expression compared to normal tissues. In the cases of different types of breast cancer, there was a significant downregulation of all subunits. The staining pattern was distinct if there could a basement membrane like structure be detected around the invading tumour nodules. When laminin and collagen type IV surrounded the tumour cells, those cells in contact with the extracellular matrix components still displayed strong positivity for the integrin subunits. Other cells inside the tumour cell nests or not surrounded by basement membrane did not express integrins. The positively staining cells might be more differentiated owing to the effect the basement membrane. Myoepithelial labeling of the integrin expressing cells gave negative results. The observed integrin expression heterogeneity renders the histologic picture difficult to interpret with regard to clinical behavior of the tumour.

[Quality of life of post-colostomy patients]. / Colostomás betegek életminöségének vizsgálata.

The psychosomatic care of patients after surgical treatment must comprise the analysis of quality of life with colostomy. Five different parameters were assessed of 100 colostomy patients. Sixty-one percent of our patients had skin irritation problems. Twenty-eight patients applied regular irrigation. Seventy-two percent of these had daily motions, 20% had bidaily, the remaining 8% had irregular bowel movements. Seventeen percent of the nonirrigating patients observed very irritating fecal discharge around the stoma. Embarrassing noises concomittant with bowel movements were observed by 42% and 45% struggled with bad odors. Irrigating patients had hardly any of these problems. For 65% of the patients the idea of having a colostoma meant the greatest psychological burden before the operation. The stress situation culminated in the immediate postoperative period in 10%. Forty percent of those asked were seriously worried about the reaction of their social environment. In 65% a significant decrease of social relations could be observed. Sixteen percent reported an increased social activity after colostomy had been performed. Sixty percent admitted considering the option of suicide at least once. Thirty-five percent revealed to have any kind of sexual problems after colostomy. Eight of our 100 colostomy patients experienced serious adverse reactions from their family members. In eighty percent of the cases family members showed great sympathy although they acted naively. The quality of life of colostomy patients may be best taken care of by qualified stomatherapists, out-patient proctology departments and the ileo-colostomy movement (ILCO).

The mouse VLA-2 homologue supports collagen and laminin adhesion but not virus binding.

Human VLA-2 (alpha 2 beta 1) mediates cellular adhesion to collagen and laminin and cell attachment by the human pathogen echovirus 1. We report here the cloning, sequencing and functional expression of the mouse VLA-2 alpha subunit homologue. This integrin subunit is closely related to its human counterpart, with 84% amino acid identity between the human and murine proteins. Conserved structural features include an identical number of amino acids, the presence of an I domain, and identity in the number and position of N-linked glycosylation sites and putative divalent cation binding regions. Murine and human alpha 2 show 30% amino acid divergence within the cytoplasmic tail, a difference that can be detected with antisera directed against the C-terminal peptides. Functionally, mouse alpha 2 was capable of mediating cell attachment to collagen and laminin, and responded to both intra- and extracellular signals with changes in its ligand affinity. In contrast, unlike its human homologue, mouse alpha 2 did not promote binding of echovirus 1. Comparison of the primary structure of the homologues leads us to predict that echovirus 1 may bind in the region of the first two thirds of the human alpha 2 I domain, where the sequences are most divergent, whereas more conserved flanking regions, and the conserved terminal one third of the I domain, may be involved in adhesion to collagen and laminin.

Factors involved in the plasminogen activation system in human breast tumours.

The plasminogen activation system is a delicately balanced assembly of enzymes which seems to have primary influence on tumour progression. The conversion of plasminogen into serine protease plasmin with fibrinolytic activity depends on the actual balance between plasminogen activators (urokinase type; u-PA and tissue type; t-PA) and their inhibitors (type 1 and 2 plasminogen activator inhibitors; PAI-1 and PAI-2). The purpose of this study was to determine the exact histological localization of all the major factors involved in plasminogen activation, and activation inhibition (plasmin system) in benign and malignant breast tumour samples. Our results show that factors of the plasmin system are present both in benign and malignant tumours. Cancer cells strongly labelled for both u-PA and t-PA, but epithelial cells of fibroadenoma samples were also stained for plasminogen activators at least as intensively as tumour cells in cancerous tissues. In fibroadenomas, all the epithelial cells were labelled for PAI-1. Staining became sporadic in malignant tumours, cells located at the periphery of tumour cell clusters regularly did not show reaction for PAI-1. In the benign tumour samples the perialveolar connective tissue stroma contained a lot of PAI-1 positive cells, showing characteristics of fibroblasts; but their number was strongly decreased in the stroma of malignant tumours. These findings indicate that the higher level of u-PA antigen, detected in malignant breast tumour samples by biochemical techniques, does not necessarily indicate increased u-PA production by tumour cells but it might be owing to the increased number of cells producing u-PA as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle.

Integrins are a class of cell adhesion molecules that participate in cell-cell and cell-substratum interactions and are present on essentially all human cells. The distribution of nine different alpha and beta integrin subunits in human endometrial tissue at different stages of the menstrual cycle was determined using immunoperoxidase staining. Glandular epithelial cells expressed primarily alpha 2, alpha 3, and alpha 6 (collagen/laminin receptors), while stromal cells expressed predominantly alpha 5 (fibronectin receptor). The presence of alpha 1 on glandular epithelial cells was cycle specific, found only during the secretory phase. Expression of both subunits of the vitronectin receptor, alpha v beta 3, also underwent cycle specific changes on endometrial epithelial cells. Immunostaining for alpha v increased throughout the menstrual cycle, while the beta 3 subunit appeared abruptly on cycle day 20 on luminal as well as glandular epithelial cells. Discordant luteal phase biopsies (greater than or equal to 3 d "out of phase") from infertility patients exhibited delayed epithelial beta 3 immunostaining. These results demonstrate similarities, as well as specific differences, between endometrium and other epithelial tissues. Certain integrin moieties appear to be regulated within the cycling endometrium and disruption of integrin expression may be associated with decreased uterine receptivity and infertility.

Distribution of integrin cell adhesion receptors in normal and malignant lung tissue.

The integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular morphology, differentiation, and proliferation. The integrin repertoire of a cell may therefore influence its behavior under resting conditions or following malignant transformation. For this reason, the distribution of integrins in normal lung tissues was determined using monoclonal antibodies against integrins of the beta 1 (VLA) and beta 3 (cytoadhesin) subfamilies and compared with the distribution in a limited number of lung carcinomas. The integrin subunits that bind to collagen and laminin (alpha 1, alpha 2, alpha 3, and alpha 6) and the alpha subunit, which can pair with beta 1, beta 3, or beta 5 and promote fibronectin, fibrinogen, or vitronectin binding, were the predominant integrins expressed on the major cell types of the lung, i.e., bronchial epithelium, vascular endothelium, and smooth muscle. Strong expression of the alpha 5 beta 1 fibronectin receptor and the beta 3 subunit was restricted to the endothelium of large vessels. Integrin expression by the lung carcinoma cells was somewhat heterogeneous; however, the tumors tended to express fewer integrins than did the normal bronchial epithelium.

Immunohistochemical and molecular analysis of beta 1 and beta 3 integrins.

The expression and function of integrin subunits was examined by immunohistochemical staining of normal and malignant tissues and by producing specific changes in avian beta subunit cDNA that were subsequently expressed in mammalian cells. Most tissues express only a restricted number of integrins. These include primarily those thought to function as collagen/laminin receptors. With the exception of metastatic melanomas, tumors show a general down regulation of integrins. Structure/function studies of the beta subunit show that the cytoplasmic domain is required for inclusion in adhesion plaques and for promotion of adhesive functions; that the transmembrane domain is required for subunit association, but not proper alpha subunit selection; and that the amino terminal one third of the subunit must remain intact for subunit selection and ligand binding to occur.

Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression.

Since tumor progression is dependent on the ability of malignant cells to interact with the extracellular matrix, molecules on the cell surface which mediate cell-substratum interactions are likely to be important regulators of tumor invasion and metastasis. The purpose of this study was to examine the distribution of one such group of cell adhesion receptors, the integrins, in benign and malignant lesions of human melanocytes. The distribution of integrin adhesion receptors was defined on cells in culture derived from normal and malignant melanocytes and in tissue sections from benign to increasingly malignant melanocytic lesions using a panel of monoclonal antibodies against specific integrin subunits. Cells in culture expressed a large variety of integrins, including all of the previously characterized members of the beta 1 subfamily plus the alpha v/beta 3 vitronectin receptor. The expression of integrins was similar in cells cultured from either benign or malignant lesions. In contrast, consistent differences were noted in integrin expression by cells within tissues containing metastatic and vertical growth phase melanomas when compared to radial growth phase melanoma cells and cells within nevi. Most notably, the expression of the beta 3 subunit was restricted exclusively to cells within vertical growth phase and metastatic melanomas. The presence of this integrin may be important in the development of tumor invasiveness and could be useful as a marker of melanoma cells entering the more aggressive phase of the malignant process.

Pathological confirmation of foetal cystic fibrosis following prenatal diagnosis.

Here we report on the results of histopathological analysis of several organs of 5 foetuses and 2 newborn infants with cystic fibrosis. They were examined with HE, PAS, AB, HID and "Stains-all" techniques on paraffin sections. We concluded that there were significant differences in the epithelial mucin composition of several organs of the effected foetuses compared to 6 controls as early as the 17th week of gestation. An increase in the amount of neutral and acidic mucins was observed in the acini of the pancreas, bronchi and the mucosa of the gastrointestinal tract accompanied with a well defined decrease of sialic acid rich components of pharyngeal submucosal glands.

The chronically furosemide-treated mouse as a possible ultrastructural model for cystic fibrosis.

The effect of chronic furosemide treatment on the structure of the secretory cells in the mouse pancreas was studied using electron microscopy. The number of the zymogen granules increased in the cytoplasm of acinar cells; they were more densely packed and had a less electron-dense appearance than the controls. Because these ultrastructural findings resemble the changes observed in exocrine glands of patients with cystic fibrosis, the chronic furosemide-treated mouse is proposed as an experimental model for this disease.