[Treatment results of patients with rectum tumor in a city hospital]. / Rectum daganatos betegek kezelésének eredményei egy városi kórházban.

INTRODUCTION: Two hundred and three patients were operated on with rectal malignancy between 2007 and 2014 in our surgical department. METHODS: Of these, patients who had cancer within 16 cm of the anal verge were included. 73 patients received neoadjuvant treatment and 130 patients were treated with primary resection. The specimens were graded by the Dworak and the Rödel regression score system. RESULTS: We found strong response in 45 patients and pathologic complete remission in three patients. 5-years survival was compared in the two groups operated between 2007 and 2009. While the overall survival rates were just the same, we can report that response to neoadjuvant therapy is a strong predictor of disease free survival. The incidence of loco-regional recurrence was lower in patients who received neoadjuvant treatment compared to the ones who underwent primary resection. Postoperative complications, incidence of anastomotic leakage were also analysed. We did not find increase in the postoperative complications in the group of patients with neoadjuvant treatment.

[The surgical case of a 34-year-old female patient with a metastatizing double colon tumor with different histological structure, causing mechanical obstruction]. / Mechanicus ileust okozó, eltéro hisztológiai szerkezetu, metastatizáló, duplex colontumor operált esete egy fiatal, 34 éves nobetegben.

We would like to present the case of a young woman (age 34) who was admitted to our department due to unbearable colicky pain, which started one week prior to her hospitalization. Examinations revealed mechanical obstruction, which is very unusual in her age without surgical history. During emergency surgery, we found descending colon tumour which was invading the abdominal wall with pelvic carcinomatosis at the border of the sigmoid colon. Due to extreme colonic dilation and impending rupture of the colonic serosa, we performed a subtotal colectomy with ileosigmoid anastomosis. In addition, pelvic peritonectomy was carried out, too. The histopathological examination of the resected part demonstrated adenocarcinoma of the descending-sigmoid colon, as well as another - histologically different - tumour (a well-differentiated neuroendocrine carcinoma [NEC]), which would not have been discovered, because it was invisible and impalpable. However, this latter tumour was responsible for the peritoneal metastases.

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease--a combined tissue microarray, in vitro and in vivo study.

BACKGROUND: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. METHODS: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. RESULTS: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents. CONCLUSIONS: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response.

[Prevalence of gastric polypoid lesions at an endoscopic facility]. / A gyomor polypoid képleteinek gyakorisága egy endoszkópos centrumban.

BACKGROUND: The prevalence of gastric polyps is unknown in Hungary. AIM: The aim of the authors was to assess the prevalence of polypoid lesions of the stomach in the endoscopic centre of the 2nd Department of Medicine, Semmelweis University. METHODS: Results of upper gastrointestinal endoscopies carried out between March 2010 and June 2011 were analysed. RESULTS: 193 cases with polyps were diagnosed in 4174 endoscopies (4.62%). Hyperplastic polyps, fundic gland polyps and malignant lesion were detected in 33.67%, 31.09% and 2.07% of the cases, respectively. Proton pump inhibitor use was more frequent among patients diagnosed with fundus gland polyps (p = 0.007), while hyperplastic polyps were diagnosed more frequently in patients with chronic gastritis (p = 0.032). CONCLUSIONS: The frequency of gastric polyps was higher than expected from data published in the literature. Long-term proton pump-inhibitor use and chronic gastritis were associated with fundus gland and hyperplastic polyps, respectively.

[Association of brownish polyposis and diverticulosis in the sigmoid colon -- a case of mucosal prolapse syndrome]. / Barnás polyposis és diverticulosis együttes elofordulása sigmabélben -- Mucosalis prolapsus syndroma esete.

The authors present a case of a 48 year-old man, who was diagnosed with several brownish sigmoid polyps of 1-2 cm size and diverticulosis on colonoscopy. Subsequently, laparoscopic sigmoid resection was carried out due to lower gastrointestinal bleeding. Histological examination revealed diverticulosis associated with polyposis. This rare entity is known in the literature as prolapse-type inflammatory polyp, which is a type of mucosal prolapse syndrome. The brownish discolouration was caused by hemosiderin deposition.

Association of collagenous colitis with prurigo nodularis.

The etiology and pathogenesis of collagenous colitis (CC) is poorly understood and probably multifactorial; many potential pathophysiological mechanisms have been described, although none have been conclusively proved. Circumstantial evidence suggests that CC appears as an autoimmune response to a luminal or epithelial antigen of unknown origin. Infections and certain drugs (e.g. NSAID, lansoprazole) may act as triggers for an immune-mediated process. CC is characterized clinically by chronic watery, nonbloody diarrhea with normal endoscopic appearance and without radiological abnormalities, but specific microscopic changes in the colon. Histopathology is featured by the presence of a thickened subepithelial collagen band adjacent to the basal membrane. Up to 40% of patients with CC have associated diseases of autoimmune or inflammatory origin, such as thyroid disease, coeliac disease, rheumatoid arthritis, diabetes mellitus, Sjögren's syndrome, CREST syndrome, scleroderma, pernicious anemia, and sarcoidosis. Prurigo nodularis is a chronic condition characterized by intensely pruritic, lichenified, or excoriated papules and nodules of unknown etiology. It is assumed to represent a cutaneous reaction pattern to repeated scrubbing or scratching caused by pruritus. We report a case of CC and prurigo nodularis. To our knowledge, this association has not been reported earlier.

Elevated insulin-like growth factor 1 receptor, hepatocyte growth factor receptor and telomerase protein expression in mild ulcerative colitis.

OBJECTIVE: The risk of development of colorectal carcinoma is elevated in chronic, long-standing ulcerative colitis (UC). The changes in regenerative and immortalizing pathways caused by the inflammatory process, and that have been proved to be carcinogenic in other human tissues, have not been fully and uniformly described. We assayed the expression alterations of regenerative signal receptors and cell-aging inhibitory systems within colonic crypts by considering the histological activity of the disease. METHODS: I-type insulin-like growth factor receptor (IGF1R), hepatocyte growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on biopsy specimens from 11 mild, 11 moderate and 12 severe active inflammation of UC cases and from 10 normal colonic tissue cases. Independent colonic biopsies from 5 healthy and 7 severe UC cases were used for TaqMan real-time RT-PCR validation. RESULTS: In mild inflammation, all observed parameters showed significantly elevated epithelial protein expression (IGF1R: 22.3 +/- 9.46%; HGFR: 35.3 +/- 22.8%; TERT/TP-1: 2.1 +/- 1.87%/2 +/- 1.32%) compared to normal (p < 0.005). In moderately active inflammation, only IGF1R expression was significantly higher (50.2 +/- 8.6%) compared to normal and mild inflammation (p < 0.005). In severe inflammation, all parameters showed decreased epithelial expression; IGF1R showed decreased mRNA expression, while HGFR was overexpressed and TERT showed a decreased tendency. CONCLUSIONS: The epithelial expression of IGF1R, HGFR and TERT/TP-1 is elevated in mildly active UC. This phenomenon may allow the epithelial cells that collected genetic defects during severe inflammatory episodes pathologically to survive and proliferate.

[Successfully treated case of postoperative mesenteric panniculitis]. / A posztoperatív mesenterialis panniculitisrol egy sikerrel kezelt eset kapcsán.

Mesenteric panniculitis can develop in every patient after abdominal surgery. The clinical and pathological signs are usually vague, so different therapeutic approaches are recommended at various stages of the disease. While some authors suggest that these stages are different manifestations of the the same disease, others claim that the various stages represent the progression of a single entity. We report a case of a 65 year-old male patient with mesenteric panniculitis and fibrosis, which developed after laparoscopic sigmoid resection first, and required a Hartmann's procedure finally. The disease developed once again after the elective reconstruction of the colon. This time surgical intervention was not possible and he was treated conservatively with intravenous steroids, antibiotics, parenteral nutrition and continuous nasogastric tube. The patient gradually recovered in three weeks time. We report this successful treatment, and review the relevant literature.

Matrix metalloproteinase-9 expression in the normal mucosa-adenoma-dysplasia-adenocarcinoma sequence of the colon.

It has been proposed that matrix metalloproteinases (MMPs) play a role in tumor invasion. We determined protein expression of matrix metalloproteinase-9 (MMP-9) in colorectal cancer (CRC), corresponding normal mucosa and colorectal adenomas. For confirmation of immunohistochemical results MMP-9 TaqMan RT-PCR analysis was performed. Expression of MMP-9 was determined on paraffin embedded biopsy sections by immunohistochemistry in 31 CRC patients (from cancer tissue and corresponding normal mucosa) and in 30 patients with adenoma (nine adenomas with high grade of dysplasia). MMP-9 immunostaining was determined semi-quantitatively. For Taqman RT-PCR analyses normal mucosa (n = 5), adenoma without (n = 6) and with high grade dysplasia (n = 7) and CRC (n = 10) were investigated. Statistical analysis with ANOVA, LSD test and correlation analysis were performed. P value of <0.05 was considered significant. The MMP-9 expression in CRC was significantly higher compared to adenomas or the normal mucosa (P = 0.001). Significantly higher expression of MMP-9 has been observed in adenomas with high grade dysplasia compared to other adenomas or normal colon (P < 0.001). Diffuse strong MMP-9 expression was present in tumor as well as in stromal cells. In adenoma samples, dysplastic epithelial cells showed moderate intensive cytoplasmic MMP-9 expression, with a clear-cut differentiation between dysplastic and non-dysplastic areas. Staining intensity correlated with the grade of CRC. We demonstrate a significantly higher expression of MMP-9 in adenoma with high grade dysplasia-CRC sequence as compared to normal tissue. The over-expression of MMP-9 strongly suggests its association with colorectal carcinogenesis.

Helicobacter pylori and antrum erosion-specific gene expression patterns: the discriminative role of CXCL13 and VCAM1 transcripts.

BACKGROUND AND AIMS: Chronic Helicobacter pylori infection affects approximately half of the world, leads to chronic gastritis and peptic ulceration, and is linked to gastric carcinoma. Our aims were to compare the gene expression profile (GEP) of H. pylori-positive and H. pylori-negative gastric erosions and adjacent mucosa to explain the possible role and response to H. pylori infection and to get erosion-related mRNA expression patterns. METHODS: Total RNA was extracted, amplified, and biotinylated from gastric biopsies of patients with H. pylori-positive and H. pylori-negative antrum erosions (ER) (8/8) and adjacent macroscopically normal mucosae (8/8). The GEP was evaluated using HGU133plus2.0 microarrays. Two independent normalizations (MAS5.0, RMA), PAM feature selection, hierarchical cluster analysis, and discriminant analysis were done. The expression of 14 genes was also measured by real-time-polymerase chain reaction. VCAM-1 and CXCL13 immunohistochemistry (IHC) was done. RESULTS: In H. pylori infection, significant overexpression of MHC class II antigen-presenting genes, interleukin-7 receptor, ubiquitin-D, CXCR4, lactoferrin immune response-related genes, CXCL-2 and -13, CCL18 chemokine ligand, and VCAM-1 genes were established. In erosive gastritis, increased proliferation (MET) and transport (UCP2, SCFD1, KPNA4) were found, while genes associated with adhesion (SIGLEC11), transcription regulation (ESRRG), and electron and ion transport (ACADM, CLIC6) were down-regulated. Discriminant analysis successfully classified all samples into four groups (HP+ER-, HP+ER+, HP-ER+, HP-ER-) using a reduced gene set (20). Significant overexpression of VCAM-1 and CXC13 protein was detected by IHC in HP+ samples (p < .05). CONCLUSIONS: Whole genomic microarray analysis yielded new H. pylori infection and erosion-related gene expression changes. Discriminative genes can be used in mRNA-based diagnostic classification of gastric biopsies.

Automated virtual microscopy of gastric biopsies.

BACKGROUND: Automated virtual microscopy of specimens from gastrointestinal biopsies is based on cytometric parameters of digitized histological sections. To our knowledge, cytometric parameters of gastritis and of adenocarcinoma have yet to be fully characterized. Our objective was to classify gastritis and adenocarcinoma based on cytometric parameters. We hypothesized that automated virtual microscopy using this novel classification can reliably diagnose gastritis and adenocarcinoma. METHODS: Routinely processed hematoxylin-and-eosin-stained histological sections from specimens that showed normal mucosa (14 cases), gastritis (35 cases), and adenocarcinoma (30 cases) diagnosed by conventional optical microscopy were scanned and digitized at high resolution. Thirty-eight cytometric parameters based on density and morphometry were applied to glands and superficial epithelium. Twelve cytometric parameters based on cytologic detail were applied to individual cells. RESULTS: Statistically significant differences in cytometric parameters for normal mucosa, gastritis, and adenocarcinoma were found. The most discriminatory parameter was the ratio of the total number of cells to the number of interstitial cells. These differences correctly classified adenocarcinoma at 100% accuracy and overall correctness was 86%. CONCLUSIONS: We describe a novel method of analyzing gastric mucosal histology based on cytometric parameters. Automated virtual microscopy can be used to classify gastric mucosa as normal, gastritis, or adenocarcinoma with reasonable accuracy. Further research is necessary to determine whether automated virtual microscopy can subclassify gastric mucosal histology in greater detail.

Smad signal and TGFbeta induced apoptosis in human lymphoma cells.

Transforming growth factor beta1 (TGF beta1) has antiproliferative and/or apoptotic effect on lymphoid cells. In certain lymphomas exogenous TGF beta1 is able to induce apoptosis, however many lymphoid malignancies are resistant to the endogenous TGF beta1 production. We studied the expression and the activity of TGF beta1 signalling components in B cell lymphoma cell lines (e.g. HT 58 cells) and in isolated human peripheral mononuclear cells (PBMCs) from healthy individual's and B-CLL patient's blood. We found that all signal transducer Smads (Smad2,-3; Smad4) and at least one of the inhibitory Smads (Smad6,-7) were expressed in non-treated lymphoma cells, but the inhibitory Smads did not in normal/control PBMCs. However, after TGF beta1 treatment Smad6 disappeared, while the expression of Smad7 increased in HT 58 cells. The activity of Smad signals was proved by phosphorylation of Smad2, nuclear translocation of Smad2/3, and the increased expression of Smad-dependent gene, TIEG in TGF beta1 treated lymphoma cells. These results showed that Smad signaling is available in certain different human lymphoma cells, however ISmads expression could inhibit the signal transmission. This findings indicates that the lost sensitivity of lymphoma cells toward a physiological regulatory factor could be reversed.

Growth in epithelial cell proliferation and apoptosis correlates specifically to the inflammation activity of inflammatory bowel diseases: ulcerative colitis shows specific p53- and EGFR expression alterations.

PURPOSE: Epithelial cell turnover related differences between ulcerative colitis, Crohn's colitis, and aspecific colitis are not known yet. METHODS: Totally 345 formalin-fixed, paraffin-embedded biopsy specimens from 33 ulcerative colitis, 26 Crohn's colitis, 30 aspecific colitis, and 10 healthy patients were observed with the TdT-mediated dUTP nick end labeling method and proliferating cell nuclear antigen-, p53-, and epithelial growth factor receptor immunohistochemistry. Because of epithelial growth factor receptor positivity of subepithelial cells epithelial growth factor receptor and CD45, CD68, or CD83 double fluorescence immunohistochemistry were performed on 16 freshly frozen samples from 8 severely active ulcerative colitis and 8 severely active Crohn's colitis patients to describe lamina propria's mononuclear cells, respectively. RESULTS: The epithelial growth factor receptor expression was significantly lower in each inflammatory group compared with normal (P < 0.005) and decreased significantly in mild ulcerative colitis compared with mild Crohn's colitis or aspecific colitis (P < 0.005). Numerous epithelial growth factor receptor and CD45 double-positive submucosal mononuclear cells were observed in moderate-severe inflammations. The p53-expression was significantly higher in each inflammatory group compared with normal (P < 0.05). Significant differences were found between mildly, moderately, and severely inflamed samples in ulcerative colitis (P < 0.05) compared with Crohn's colitis or aspecific colitis. Apoptotic/proliferative rates increased significantly in line with the inflammatory process (P < 0.0001/0.05), but the TdT-mediated dUTP nick end labeling and proliferating cell nuclear antigen-labeling characteristics did not show disease type specificity. CONCLUSIONS: Based on our results, the alterations of epithelial growth factor receptor and p53 expression show ulcerative colitis specificity, whereas the rate of epithelial apoptosis and proliferation are determined by the histologic activity of the inflammation. The increased epithelial growth factor receptor expression by the lamina propria's mononuclear cells in inflammation may suggest its role as an autoantigen.

[Ileocecal intussusception caused by Burkitt lymphoma, cause of mechanical ileus]. / Ileocoecalis intussusceptiót elóidézó Burkitt-lymphoma, mint mechanikus ileus oka.

A 39-year-old man was admitted to our Medical Department, because of regular abdominal cramps. At physical examination a palpable mass was detected in the ileocoecal region with tenderness. Examinations proved ileocoecal intussusception. Emergency operation was performed. At histology the cause of small-bowel invagination was Burkitt-lymphoma. After the complex haematological examination chemotherapy was started. Six month after surgery the patient is symptomless.

[Massive gastrointestinal bleeding in Henoch-Schoenlein purpura in an adult]. / Masszív gasztrointesztinális vérzés felnóttkori Schónlein-Henoch purpurában.

Henoch-Schoenlein syndrome in an adult patient, localised only to the gastrointestinal system is very rare. A 50 year old male was treated in our Intensive Department because of acute respiratory distress syndrome (ARDS) and renal failure. After temporary improvement massive gastrointestinal bleeding developed with shock. Blood was found in the descending duodenum without evident pathology at endoscopy. Angiogram showed bleeding at the hepatic flexure of the colon, which was successfully treated by a coil and bleeding was also present in the terminal part of the small intestine. The catheter was left in situ and the bleeding part of the bowel was painted intraoperatively, so we could resect the stained part of the intestine. Because of rebleeding, bowel resection was performed an other two occasions in the same way. The histology of the bowel showed Henoch-Schoenlein syndrome in each specimen. Our patient was totally non-responsive to treatment, which is usually successful in this disease. After the resections the bleeding stopped temporarily, but as the underlying disease was unmanageable the patient died but we have not found any surgical complication at autopsy. We think that this method in the surgical treatment of massive intestinal bleeding is very useful and effective.

Detection of Drug-induced Apoptosis by Flow Cytometry after Alkaline Extraction of Ethanol Fixed Cells.

A new flow cytometric method was developed to detect apoptotic cells with fragmented DNA and to determine cell cycle distribution of viable cells, in the same sample, by propidium iodide staining. Apoptosis, in HT58 human B lymphoma cells, was induced by etoposide and/or by staurosporine. Using appropriate alkaline solutions (between 1-10 mN NaOH in 150 mM saline) followed by neutralization with buffer solution, the fragmented DNA can be extracted quantitatively from ethanol fixed cells. Further, good resolution of the cell cycle distribution can be obtained in unimpaired cells without RNase treatment. Furthermore, unlike the widely used hypotonic-detergent extraction of unfixed cells, the suggested extraction method can prevent drug-induced disintegration of dead cells when karyorrhexis occurs.

Eosinophils and Mast Cells in Helicobacter Pylori Infected Gastric Mucosa.

Although Helicobacter pylori (HP) is frequently associated with chronic active gastritis and peptic ulcers, its exact pathogenic role or the pathomechanism is still unclear. Here, we describe a striking, statistically significant increase of eosinophils in HP infected gastric mucosa compared to HP negative gastritis with similar activity. In both cases, the mean number of the mast cells in the mucosa was comparable, although the individual values showed wide distribution. The source and role of eosinophilia in HP infected mucosa, the potential link between the degree of eosinophilia and the clinical progression, as well as between eosinophils and mast cells require further study.