Detailed esophageal function and morphological analysis shows high prevalence of gastroesophageal reflux disease and Barrett's esophagus in patients with cervical inlet patch.

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.

A renewed insight into Barrett's esophagus: comparative histopathological analysis of esophageal columnar metaplasia.

Specialized intestinal metaplasia (SIM) is considered as a premalignant condition of the esophagus, but other types of esophageal metaplasia are commonly neglected. A standardized histopathological analysis was focused not only on SIM but also on the presence of metaplastic processes typical of additional glands. A morphological study using standardized histopathological tests was carried out between 2004 and 2007, with biopsies taken from esophageal mucosa of 826 consecutive patients. Mean age and male : female ratio of patients were 55.6 ± 14.7 and 1.1 : 1, respectively. Only 4.1% (n = 34) of all cases proved to have SIM. The remainder of the cases (n = 615; 74.4%) contained cardiac-fundic mucosa without SIM. Some samples exhibited superficial mucous glands, pancreatic acinar metaplasia (PAM), and ciliated metaplasia accounting for 24% (n = 198), 14.9% (n = 123), and 0.2% (n = 2), respectively. SIM was colocalized with superficial mucous glands (103/198 superficial mucous gland cases; P < 0.001). Low-grade dysplasia (n = 51; 6.2%) and high-grade dysplasia (n = 9; 1.1%) were found mainly in SIM (37/51; 9/9; P = 0.071) with male preponderance (3 : 1 at low-grade and 2 : 1 at high-grade dysplasia). PAM was found mainly in cases without dysplasia (103 of 123 pancreatic metaplasias; P < 0.001). SIM alone in the esophagus is rare, and its frequent association with cardiac mucosa-type metaplasia testifies to transition of mucinous-goblet cell through pseudogoblet cells. PAM rather indicates absence of dysplasia, but superficial mucous glands predicts that SIM follows dysplasia.

Helicobacter pylori induces the release of alpha-defensin by human granulocytes.

OBJECTIVES: Little information is available on the potential role of alpha-defensins derived from neutrophils during H. pylori infection, or the effect of H. pylori on the alpha-defensin release. The effects of H. pylori on human granulocytes were investigated in vitro by flow cytometry and ELISA. Additionally we sought to identify by immunohistochemistry the alpha-defensins within the gastric mucosa of patients infected with H. pylori. MATERIALS AND METHODS: The intracellular expression of alpha-defensin in human granulocytes and in mononuclear cells was determined by flow cytometry. Induction of alpha-defensin release from granulocytes, mononuclear cells, or from whole blood cultures by H. pylori was detected by measuring the HNP1-3 (alpha-defensin) concentrations in the supernatants by ELISA. Immunohistochemistry was used to identify HNP1-3 in infiltrating neutrophils in the gastric mucosa of eight patients. RESULTS: A considerable intracellular alpha-defensin staining was observed in granulocytes. Stimulation of granulocytes with H. pylori resulted in a decrease in intracellular staining which was due to the extracellular release of alpha-defensin. In whole blood cultures H. pylori infection resulted in significantly high alpha-defensin concentrations (131623 +/- 13986 pg/ml), which were mainly due to the activity of the granulocytes with only a minor amount furnished by the mononuclear cells. In H. pylori-infected mucosa, infiltrating neutrophils showed intense immunostaining with anti-HNP1-3. The intensity of alpha-defensin staining varied parallel with the density of H. pylori in the biopsy samples. CONCLUSIONS: H. pylori induce alpha-defensin release from granulocytes which may well be important in local host response to H. pylori infection in gastroduodenal diseases.

Detection of nanobacteria-like particles in human atherosclerotic plaques.

Recent and historical evidence is consistent with the view that atherosclerosis is an infectious disease or microbial toxicosis impacted by genetics and behavior. Because small bacterial-like particles, also known as nanobacteria have been detected in kidney stones, kidney and liver cyst fluids, and can form a calcium apatite coat we posited that this agent is present in calcified human atherosclerotic plaques. Carotid and aortic atherosclerotic plaques and blood samples collected at autopsy were examined for nanobacteria-like structures by light microscopy (hematoxylin-eosin and a calcium-specific von Kossa staining), immuno-gold labeling for transmission electron microscopy (TEM) for specific nanobacterial antigens, and propagation from homogenized, filtered specimens in culture medium. Nanobacterial antigens were identified in situ by immuno-TEM in 9 of 14 plaque specimens, but none of the normal carotid or aortic tissue (5 specimens). Nanobacteria-like particles were propagated from 26 of 42 sclerotic aorta and carotid samples and were confirmed by dot immunoblot, light microscopy and TEM. [3H]L-aspartic acid was incorporated into high molecular weight compounds of demineralized particles. PCR amplification of 16S rDNA sequences from the particles was unsuccessful by traditional protocols. Identification of nanobacteria-like particles at the lesion supports, but does not by itself prove the hypothesis that these agents contribute to the pathogenesis of atherosclerosis, especially vascular calcifications.

Recovery of exocrine pancreas six months following pancreatitis induction with L-arginine in streptozotocin-diabetic rats.

The aim of the present work was to investigate the laboratory and morphologic alterations in the pancreas 6 months after pancreatitis induction with L-arginine (Arg) in normal and streptozotocin (STZ)-diabetic rats. The amylase content of the pancreas was significantly decreased in the Arg-treated groups vs. the control group. No significant changes were observed in the DNA, soluble protein and lipase contents of the pancreas. In the STZ-treated groups, the serum glucose level was significantly elevated, whereas the serum immunoreactive insulin (IRI) level was significantly decreased vs. the control group. In these treated groups, the amylase content of the pancreas was also significantly decreased, but that of trypsinogen was significantly elevated vs. the control group. Histologic sections revealed periductal fibroses, adipose tissue and tubular complexes in the Arg-treated rats, but centroacinar hyperplasia was not observed in these groups. No alterations were observed on histological examination in the diabetic rats vs. normal rats 6 months following pancreatitis induction. In conclusion, a major restitution of the pancreatic enzyme content, but moderate histologic alterations were detected 6 months following pancreatitis induction with Arg. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this long-term study, but not to modify the recovery of the exocrine pancreas 6 months following Arg-induced pancreatitis.

The pathogenesis of L-arginine-induced acute necrotizing pancreatitis: inflammatory mediators and endogenous cholecystokinin.

This study was aimed at an assessment of the role of oxygen-derived free radicals, cytokines and endogenous cholecystokinin (CCK) in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat. We measured the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn- and Cu, Zn-SOD) in pancreatic tissue, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and CCK, and evaluated the protective effect of the xanthine oxidase inhibitor allopurinol and a novel CCK receptor antagonist KSG-504. Acute pancreatitis was induced in male Wistar rats by injecting 2x 250 mg/100 g body weight of Arg intraperitoneally in an 1-h interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. 200 mg x kg(-1) allopurinol 30 min before the first Arg treatment or 50 mg x kg(-1) KSG-504 30 min before and 6, 18 and 36 h after the first Arg injection was administered subcutaneously. Rats were killed at 6, 12, 24 and 48 h following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 h after the Arg injection (30,800 +/- 3,813 versus 6,382 +/- 184 U x L(-1) in the control) and normalized at 48 h. The tissue concentration of MDA was significantly elevated at 24 h, and reached the peak value at 48 h (5.00 +/- 1.75 versus 0.28 +/- 0.05 nM x mg(-1) protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 h, and the Cu, Zn-SOD activity was significantly lower at 12 h after the Arg injection as compared with the controls. Both the TNF-alpha and the IL-6 levels were already elevated significantly at 12 h and peak at 24 h versus the controls (19.1 +/- 7.9 U x mL(-1) and 57.6 +/- 11.2 pg x mL(-1) versus 3.1 +/- 0.8 U x mL(-1) and 15.2 +/- 3.1 pg x mL(-1), respectively). No significant changes in plasma CCK levels were observed. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 +/- 2.257 U x L(-1) at 24 h), prevented the increase in tissue MDA concentration (0.55 +/- 0.09 nM x mg(-1) protein at 48 h) and significantly ameliorated the pancreatic edema, necrosis and inflammation at 48 h after Arg administration. KSG-504 administration did not exert any beneficial effect on the development of histopathological changes neither modified the serum amylase or cytokine levels. Oxygen-derived free radicals and cytokines are involved, while endogenous CCK does not seem to play a role in the pathogenesis of Arg-induced acute pancreatitis.

Surgical intervention for pulmonary tuberculosis: analysis of indications and perioperative data relating to diagnostic and therapeutic resections.

OBJECTIVE: To analyze the data on patients operated on for pulmonary tuberculosis (TB) with (Group I) or without (Group II) a correct TB diagnosis and preoperative anti-TB treatment. METHODS: Between 1980 and 1997, 144 resections for TB (Groups I+II) were performed. The 80 patients in Group I underwent therapeutic resections: 32 cases involved recurrent cavities or tuberculomas, three involved post-TB bronchiectasis, 13 involved progression of cavities or tuberculomas, and 32 involved persistent tuberculomas after 6 months of anti-TB therapy. The 64 patients in Group II were operated on for a suspicion of malignancy in 49 cases, for cavitary lesions with haemophthysis in six cases, for multiple lesions in seven cases, and for recurrent hydrothorax in two cases. RESULTS: Groups I and II included 0 and five pneumonectomies, 32 and 29 lobectomies, 48 and 20 wedge resections, 0 and nine videothoracoscopic biopsies, and 0 and one hilar lymphadenectomy, respectively. In Groups I and II, the mean duration of postoperative hospitalization was 13.2 and 10.4 days, and the frequency of postoperative pneumothorax was 11.25 and 4.6%, respectively. The incidence of bronchopleural fistula was 1.25 and 0%, the mortality was 0 and 3.1%, and the morbidity was 53.7 and 35.9% in Groups I and II, respectively. Two patients with active disease died in Group II. Pathology demonstrated that the frequency of acid-fast bacilli in Groups I and II was 40 and 25%, respectively. CONCLUSIONS: Patients without a correct preoperative TB diagnosis underwent more extensive parenchyma resection. Postoperative complications increased when acid-fast bacilli were present. The lack of preoperative anti-TB treatment did not involve a higher risk of minor complications, but death occurred only in this group.

Multiple primary intracranial tumors and association of intra- and extracranial tumors. An autopsy study.

In 37504 autopsies performed during the last 3 decades at the Department of Pathology of Albert Szent-Györgyi Medical University (Szeged, Hungary) gliomas were found in 498 cases. These gliomas were associated with other types of intra- or extracranial tumors in 1.2-3.2% of the cases. Despite the male predominance observed in other types of multiple tumors, the multiple intracranial tumors and the intracranial tumors associated with extracranial malignancies were more frequent in females (possible role of hormonal influences). A relatively frequent association of various intracranial tumors with gastrointestinal carcinomas and in one quarter of the cases with extracranial benign tumors indicates that genetic factors may be involved in the pathomechanism.

Leiomyosarcoma of the larynx. Review of the literature and report of two cases.

Leiomyosarcoma of the larynx is an extremely rare malignancy. Until now, only 35 cases have been reported, and only 19 were reported in English. We present 2 new cases observed in the last 3 years at our department. Correct histologic diagnosis can only be made on immunohistochemical and electron microscopic grounds. A 65-year-old man previously treated for a premalignant vocal cord lesion and a 31-year-old woman who previously underwent operation on a benign vocal cord lesion are presented. Only surgical treatment (total laryngectomy and endolaryngeal laser resection) was performed. Thirty-six and 22 months after the initial surgical intervention, both patients are alive and well, with no evidence of local recurrence or distant metastasis.

Chronic recurrent transverse myelitis or multiple sclerosis.

The simultaneous occurrence of multiple sclerosis and transverse myelitis is known in the literature. Apart from the spinal symptoms, other neurological signs of brain involvement are usually found and magnetic resonance imaging (MRI) reveals disseminated foci in the brain. The positive evoked responses, the immunological abnormalities of the cerebrospinal fluid (CSF), and the oligoclonality together prove the presence of multiple sclerosis. In these cases the symptoms of transverse myelitis can separately precede other signs of multiple sclerosis, or appear as a relapse. Recurrent transverse myelitis as an independent entity, with negative MRI and CSF immunology, is an exciting topic in terms of the etiological factors and therapeutic considerations. The view in the literature is that the occurrence of transverse myelitis as an independent entity is rather rare. The present article reports the case of a female patient with recurrent spinal cord signs, and negative MRI and CSF immunology. During a ten-year follow-up observation period, symptoms of multiple sclerosis did not develop. Further studies of such cases are needed in order to clarify the etiological factors, the pathomechanism and the therapeutic considerations relating to this relatively new and probably independent clinical entity.

Thoracic core needle biopsy using ultrasound guidance.

This article demonstrates the usefulness of ultrasound (US)-guided core needle biopsy in the diagnosis of thoracic lesions. Between January 1997 and June 2000, 45 US-guided core needle biopsies were performed in the department of radiology. This method was chosen in every case when the lesion abutted the chest wall. Conventional histologic examinations supplemented by immunohistochemical methods were performed. The location and size of the mass, the number of samplings, the needle size, the histologic results, and any complications were recorded. Twenty-two lesions reached the anterior, six reached the lateral, and 14 reached the posterior chest wall. Biopsies were performed on three masses from the supraclavicular region. The mean diameter was 4.5 cm and the number of passes was 1.8; 18-G, 16-G, and 14-G needles were used in 41, two, and two cases, respectively. In 43 of the 45 cases (95.68%), an exact histologic diagnosis could be provided. In two cases, only necrotic tissue was seen in the biopsy sample. No major complications occurred. Minor complications, including pain and collaptiform weakness, were documented in four patients. Ultrasound-guided core needle biopsy of thoracic lesions is a safe, quick, and accurate method. For diagnosing thoracic lesions, a single sample with an 18-G biopsy needle is sufficient to achieve a final diagnosis when using appropriate histologic methods.

[Splenic metastases]. / A lépáttétekröl.

Splenic metastases were found in 58 cases (3.1%) at autopsy out of 1842 widely disseminated solid tumors: melanomas, carcinomas of the lung those of the breast, uterus and liver being the most common primary tumors. This rare hematogenous metastatic spread could develop due to portal congestion.

[Stomach cancer metastasizing into a solitary adenomatous colonic polyp]. / Gyomorrák áttéte soliter adenomatosus colonpolypban.

A 69-year-old man with known diffuse type gastric stump carcinoma was found at autopsy to have widely disseminated metastasis of this cancer. Metastasis also occurred in the adenomatous polyp of the cecum. This is the third report, to our knowledge, in the literature and the first Hungarian publication of a metastasis to an adenomatous polyp of the colon.

[Multiple primary malignant tumors involving the liver]. / A májat is érintö többszörös elsödleges rosszindulatú daganatok.

In the autopsy material of the Department of Pathology of Albert Szent-Györgyi Medical University 167 primary liver cancers were observed in 30 years, from which 13 patients (7.8%) had also other primary malignancies. The tumour-associations were mainly synchronously, there was strong male predominance. In 9 cases the hepatocellular carcinoma originated in cirrhotic liver. The most frequent extrahepatic tumours were found in the lungs (5 cases), smoking was among the anamnestic data.

[Malignant tumors associated with thyroid cancer in an autopsy material]. / Pajzsmirigyrákhoz társuló malignus tumorok autopsziás anyagban.

In the Department of Pathology of Albert Szent-Györgyi Medical University at Szeged in Hungary 37,504 autopsies were performed in the last 30 years and double multiple primary malignant tumours were found in 385 cases (4.2%). In thyroid cancer cases the tumours of other organs were more frequent (22.7%), and these tumour-associations were observed mainly simultaneously, there were no important sex differences. In the most of cases the thyroid cancer was only a side diagnosis beside other malignancies, in the more rare metachronous cases the thyroid cancer was secondary following postoperative irradiation of the first tumour (4 cases of 5). We have seen thyroid cancers most frequently together with lung, breast and digestive system tumours.

[The pattern of p53 oncoprotein expression in gastric cancer patients]. / A p53 onkoprotein elöfordulásának sajátosságai gyomorrákos betegekben.

The p53 gene mutation or p53 oncoprotein overexpression are the most common genetic alterations in human tumors. Its expression is known to be present in a number of tumors however, its prognostic value in gastric cancer is uncertain. The authors studied the pattern of p53 oncoprotein expression in 45 advanced gastric cancer cases. Statistically, the correlation between p53 expression and histologic type of the tumors was significant (p < 0.001): 84% of the intestinal type tumors showed positivity, in half of those (15/31, 48.3%) the positivity involved almost all of the nuclei. This is much higher than any other data in the literature. Moreover, significant correlation was found between tumor stages pT2-3 and p53 oncoprotein expression. There was no significant correlation between lymph node involvement, as one of the most important prognostic factors, and p53 expression. Their results show that the pattern of p53 gene mutation in these gastric cancer patients differs from international data, which might be caused by certain carcinogenic effects: e.g. nutritional customs characteristic of Hungary.

[Multiple primary malignant tumors involving the liver]. / A tüdöt is érintö multiplex primer malignus tumorok.

In the Department of Pathology of the Albert Szent-Györgyi Medical University in Szeged during the last 30 years 1770 (19.4% of the cancers) primary malignant lung tumours were observed in autopsy material, from which 86 patients (4.9%) had other malignancies as well. In 81 cases other extrapulmonary and in 5 cases other primary lung tumours were observed. The male predominance in these cases was significant. All of the patients were heavy smokers. Amongst these synchronous tumour-associations the most frequent extrapulmonary tumours arose in the urogenital tract, in the head and neck, relatively frequently also in the breast, liver, stomach, intestine and thyroid. These cases caused diagnostic dilemmas both for the clinician and even for the pathologist. Several signs help to distinguish a new primary tumour from a metastasis. Multiplicity itself does not mean poorer prognosis. Each cancer should possibly receive adequate treatment.

[Multiple urologic tumors in autopsy material]. / Urológiai multiplex tumorok autopsiás anyagban.

In autopsy material of the Department of Pathology at the Albert Szent-Györgyi Medical University in 16.8% of kidney cancers, in 12.5% of urinary bladder cancers and in 21.8% of prostatic cancers were second primary malignant tumours observed in the urinary system or in other organs. The cause of the relatively frequent tumour-associations can partly be explained with the high average age (72 years). The uropoetic cancers were in association with lung cancers (role of tobacco smoking?), gastrointestinal tumours (role of genetic or dietary factors?); and the prostatic carcinomas with urinary bladder cancer and hematologic malignancies. In our material testicular cancers were never associated with other malignancies.