Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity.

Pulmonary adenocarcinomas (pADCs) with an ALK rearrangement are a rare cancer subtype, necessitating comprehensive molecular investigations to unravel their heterogeneity and improve therapeutic strategies. In this pilot study, we employed spatial transcriptomic (NanoString GeoMx) and proteomic profiling to investigate seven treatment-naïve pADCs with an ALK rearrangement. On each FFPE tumor slide, 12 smaller and 2-6 larger histopathologically annotated regions were selected for transcriptomic and proteomic analysis, respectively. The correlation between proteomics and transcriptomics was modest (average Pearson's r = 0.43 at the gene level). Intertumoral heterogeneity was more pronounced than intratumoral heterogeneity, and normal adjacent tissue exhibited distinct molecular characteristics. We identified potential markers and dysregulated pathways associated with tumors, with a varying extent of immune infiltration, as well as with mucin and stroma content. Notably, some markers appeared to be specific to the ALK-driven subset of pADCs. Our data showed that within tumors, elements of the extracellular matrix, including FN1, exhibited substantial variability. Additionally, we mapped the co-localization patterns of tumor microenvironment elements. This study represents the first spatially resolved profiling of ALK-driven pADCs at both the gene and protein expression levels. Our findings may contribute to a better understanding of this cancer type prior to treatment with ALK inhibitors.

The genomic imprint of cancer therapies helps timing the formation of metastases.

A retrospective determination of the time of metastasis formation is essential for a better understanding of the evolution of oligometastatic cancer. This study was based on the hypothesis that genomic alterations induced by cancer therapies could be used to determine the temporal order of the treatment and the formation of metastases. We analysed the whole genome sequence of a primary tumour sample and three metastatic sites derived from autopsy samples from a young never-smoker lung adenocarcinoma patient with an activating EGFR mutation. Mutation detection methods were refined to accurately detect and distinguish clonal and subclonal mutations. In comparison to a panel of samples from untreated smoker or never-smoker patients, we showed that the mutagenic effect of cisplatin treatment could be specifically detected from the base substitution mutations. Metastases that arose before or after chemotherapeutic treatment could be distinguished based on the allele frequency of cisplatin-induced dinucleotide mutations. In addition, genomic rearrangements and late amplification of the EGFR gene likely induced by afatinib treatment following the acquisition of a T790M gefitinib resistance mutation provided further evidence to tie the time of metastasis formation to treatment history. The established analysis pipeline for the detection of treatment-derived mutations allows the drawing of tumour evolutionary paths based on genomic data, showing that metastases may be seeded well before they become detectable by clinical imaging.

Tumor necrosis correlates with PD-L1 and PD-1 expression in lung adenocarcinoma.

Background: Predictive biomarkers for immunotherapy in lung cancer are intensively investigated; however, correlations between PD-L1/PD-1 expressions and clinical features or histopathological tumor characteristics determined on hematoxylin and eosin stained sections have not extensively been studied. Material and methods: We determined PD-L1 expression of tumor cells (TC) and immune cells (IC), and PD-1 expression of IC by immunohistochemistry in 268 lung adenocarcinoma (LADC) patients, and correlated the data with smoking, COPD, tumor grade, necrosis, lepidic growth pattern, vascular invasion, density of stromal IC, and EGFR/KRAS status of the tumors. Results: There was a positive correlation between PD-L1 expression of TC and IC, as well as PD-L1 and PD-1 expression of IC. Tumor necrosis was associated with higher PD-L1 expression of TC and PD-1 expression of IC. A negative correlation was observed between lepidic growth pattern and PD-L1 expression of TC and PD-L1/PD-1 expression of IC. EGFR mutation seemed to negatively correlate with PD-1 expression of IC, but this tendency could not be verified when applying corrections for multiple comparisons. No significant effect of the KRAS mutation on any of the studied variables could be established. Conclusion: Here we first demonstrate that the presence of necrosis correlates with higher PD-L1 expression of TC and PD-1 expression of IC in LADC. Further studies are required to determine the predictive value of this observation in LADC patients receiving immunotherapy.

Comparative endoscopic anatomic description of the mitral valvular complex: a cadaveric study.

BACKGROUND: We compared the aortic, left atrial, and apical approaches to visualize the mitral valve with the goal to investigate the endoscopic anatomy and give exact step-by-step descriptions of these views. MATERIALS AND METHODS: The mitral valvular complex of human cadaveric fresh hearts was investigated from three approaches using 0, 30, and 70 degrees rigid endoscopic optics. In 30 cases after the removal of the hearts, the endoscopes were introduced directly into the aortic root through an aortotomy, left atrium through a standard atriotomy, and apex of the heart through a transmural incision. In 10 cases, the in situ visualization was performed using standard surgical approaches, such as partial upper ministernotomy, right and left minithoracotomy. The investigation was performed first with the mitral valve open, then the left ventricle was filled with saline, and the valve was closed by clamping the aorta. RESULTS: For the visualization of ventricular surfaces of the mitral leaflets and the subvalvular apparatus, the apical approach was most optimal. The aortic approach had limitations at the posterior leaflet. Using the atrial approach, we did not obtain any direct visual information about the subvalvular apparatus with the valve closed. The atrial surfaces of the leaflets were best visible using both the atrial and apical approaches with the mitral valve open. In the case of a closed valve, the apical approach did not allow for an investigation of the atrial surfaces. The aortic approach was useful to visualize the atrial surface of the posterior leaflet with an opened valve. CONCLUSION: In mitral valve repairs through the left atrium, an additional aortic or apical view could be useful to obtain functional information about the subvalvular apparatus by the sealing probe.

Autopsy findings in cancer patients infected with SARS-CoV-2 show a milder presentation of COVID-19 compared to non-cancer patients.

COVID-19, caused by SARS-CoV-2, manifests with differing severity across distinct patient subgroups, with outcomes influenced by underlying comorbidities such as cancer, which may cause functional and compositional alterations of the immune system during tumor progression. We aimed to investigate the association of SARS-CoV-2 infection and its complications with cancer in a large autopsy series and the role of COVID-19 in the fatal sequence leading to death. A total of 2641 adult autopsies were investigated, 539 of these were positive for SARS-CoV-2. Among the total number of patients analyzed, 829 had active cancer. Overall, the cohort included 100 patients who simultaneously had cancer and SARS-CoV-2 infection. The course of COVID-19 was less severe in cancer patients, including a significantly lower incidence of viral and bacterial pneumonia, occurring more frequently as a contributory disease or coexisting morbidity, or as SARS-CoV-2 positivity without viral disease. SARS-CoV-2 positivity was more frequent among non-metastatic than metastatic cancer cases, and in specific tumor types including hematologic malignancies. COVID-19 was more frequently found to be directly involved in the fatal sequence in patients undergoing active anticancer therapy, but less frequently in perioperative status, suggesting that the underlying malignancy and consequent surgery are more important factors leading to death perioperatively than viral disease. The course of COVID-19 in cancer patients was milder and balanced during the pandemic. This may be due to relative immunosuppressed status, and the fact that even early/mild viral infections can easily upset their condition, leading to death from their underlying cancer or its complications.

Neurochemical mapping of the human hippocampus reveals perisynaptic matrix around functional synapses in Alzheimer's disease.

Perineuronal matrix is an extracellular protein scaffold to shape neuronal responsiveness and survival. Whilst perineuronal nets engulf the somatodendritic axis of neurons, axonal coats are focal extracellular protein aggregates surrounding individual synapses. Here, we addressed the chemical identity and subcellular localization of both perineuronal and perisynaptic matrices in the human hippocampus, whose neuronal circuitry is progressively compromised in Alzheimer's disease. We hypothesized that (1) the cellular expression sites of chondroitin sulphate proteoglycan-containing extracellular matrix associate with specific neuronal identities, reflecting network dynamics, and (2) the regional distribution and molecular composition of axonal coats must withstand Alzheimer's disease-related modifications to protect functional synapses. We show by epitope-specific antibodies that the perineuronal protomap of the human hippocampus is distinct from other mammals since pyramidal cells but not calretinin(+) and calbindin(+) interneurons, neurochemically classified as novel neuronal subtypes, lack perineuronal nets. We find that cartilage link protein-1 and brevican-containing matrices form isolated perisynaptic coats, engulfing both inhibitory and excitatory terminals in the dentate gyrus and entorhinal cortex. Ultrastructural analysis revealed that presynaptic neurons contribute components of perisynaptic coats via axonal transport. We demonstrate, by combining biochemical profiling and neuroanatomy in Alzheimer's patients and transgenic (APdE9) mice, the preserved turnover and distribution of axonal coats around functional synapses along dendrite segments containing hyperphosphorylated tau and in amyloid-ß-laden hippocampal microdomains. We conclude that the presynapse-driven formation of axonal coats is a candidate mechanism to maintain synapse integrity under neurodegenerative conditions.

Anatomical changes in occipitalization: is there an increased risk during the standard posterior approach?

PURPOSE: The purpose of this study was to examine the anatomic changes in a case of occipitalization of the atlas. METHODS: Occipitalization of the atlas was found accidentally in a 64-year-old male cadaver. Anatomic dissection was carried out to examine the posterior aspect of the upper cervical region and craniocervical junction. The occipitalized atlas was then harvested and macerated to study the bony anomaly. RESULTS: In this case of occipitalization, fusion was observed at both lateral masses and at the left posterior hemiarch of the atlas. We found the following soft tissue changes: the rectus capitis posterior minor muscle was lacking on the left side and was atrophic on the right, the obliquus capitis superior muscle was present on both sides showing moderate atrophy and fatty changes. The posterior atlanto-axial membrane was thinner and asymmetric, had a free edge on the right side. Lateral to this edge the dura was lying free. We believe that these changes of the posterior atlanto-axial membrane together with the increased distance between the fused posterior arch of the atlas and the lamina of the axis could cause the observed "dura bulge" at this level. The vertebral artery was entering the skull through a canal on the left side. CONCLUSIONS: In our case, occipitalization considerably changed the anatomy of the upper cervical spine and craniocervical junction. Special care must be taken when using the posterior approach to avoid neurovascular injury in cases with occipitalization.

The lower nasal base: an anatomical study.

Currently, most rhinoplasty surgeons focus their analysis and operative techniques on the upper nasal base, with its alar cartilages. They tend to minimize the lower nasal base, composed of the columellar base, nostril sills, and alar lobules. The requisite operative techniques are often considered ancillary techniques. In this article, the authors describe anatomical composition of the columellar base, nostril sill, and alar lobule; discuss the presence of a distinct lower nasal base; and reevaluate the nasal musculature and the nasal superficial muscular aponeurotic system in an anatomical cadaver model. They also discuss the results of both a detailed literature review (for articles related to the levator labii superioris alaeque nasalis, orbicularis oris, depressor septi nasalis, myrtiformis, and dilator naris) and the results of their own dissection of 45 fresh cadavers.

Early histopathological changes of secondary degeneration in the spinal cord after total MCA territory stroke.

Previous research has not demonstrated secondary degeneration of the spinal cord (SpC) motoneurons after cerebral infarct. The aim of the present study is to investigate the involvement of the anterior horn cells (AHC) in the early post-stroke period using histomorphological and immunohistochemical methods. Post-mortem analysis of the 6th cervical segment was performed in 7 patients who had total MCA stroke within 1 month before death. Nissl-stained sections were used for morphometry, while CD68 and synaptophysin (SYP) immunohistochemistry to monitor microglial activation and synaptic changes in the anterior horn (AH), respectively. Contralateral to the cerebral lesion (contralesional side), cells were smaller after 3 days and larger after 1 week of stroke, especially regarding the large alpha motoneurons. CD68 density increased mainly on the contralesional Rexed's IX lamina of the SpC. SYP coverage of the large motoneurons was reduced on the contralesional side. Early microglial activation in the AH and electrophysiological signs has suggested the possibility of impairment of anterior horn cells (AHC-s). Our study supported that early microglial activation in the contralesional side of the SpC may primarily affect the area corresponding to the location of large motoneurons, and is accompanied by a transient shrinkage followed by increase in size of the large AHC-s with a reduction of their synaptic coverage. After MCA stroke, early involvement of the SpC motoneurons may be suspected by their morphological and synaptic changes and by the pattern of microglial activation.

Liver alterations and detection of SARS-CoV-2 RNA and proteins in COVID-19 autopsies.

The most severe alterations in Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection are seen in the lung. However, other organs also are affected. Here, we report histopathologic findings in the liver and detection of viral proteins and RNA in COVID-19 autopsies performed at the Semmelweis University (Budapest, Hungary). Between March 2020 through March 2022, 150 autopsies on patients who died of COVID-19 were analyzed. Cause-of-death categories were formed based on the association with SARS-CoV-2 as strong, contributive, or weak. Samples for histopathologic study were obtained from all organs, fixed in formalin, and embedded in paraffin (FFPE). Immunohistochemical study (IHC) to detect SARS-CoV-2 spike protein and nucleocapsid protein (NP), CD31, claudin-5, factor VIII, macrosialin (CD68), and cytokeratin 7, with reverse transcriptase polymerase chain reaction (RT-PCR), and in situ hybridization (ISH, RNAscope®) for SARS-CoV-2 RNA were conducted using FFPE samples of livers taken from 20 autopsies performed ≤ 2 days postmortem. All glass slides were scanned; the digital images were evaluated by semiquantitative scoring and scores were analyzed statistically. Steatosis, single-cell and focal/zonal hepatocyte necrosis, portal fibrosis, and chronic inflammation were found in varying percentages. Sinusoidal ectasia, endothelial cell disruption, and fibrin-filled sinusoids were seen in all cases; these were assessed semiquantitatively for severity (SEF scored). SEF scores did not correlate with cause-of-death categories (p = 0.92) or with severity of lung alterations (p = 0.96). SARS-CoV-2 RNA was detected in 13/20 cases by PCR and in 9/20 by ISH, with IHC demonstration of spike protein in 4/20 cases and NP in 15/20. Viral RNA and proteins were located in endothelial and Kupffer cells, and in portal macrophages, but not in hepatocytes and cholangiocytes. In conclusion, endothelial damage (SEF scores) was the most common alteration in the liver and was a characteristic, but not specific alteration in COVID-19, suggesting an important role in the pathogenesis of COVID-19-associated liver disease. Detection of SARS-CoV-2 RNA and viral proteins in liver non-parenchymal cells suggests that while the most extended primary viral cytotoxic effect occurs in the lung, viral components are present in other organs too, as in the liver. The necrosis/apoptosis and endothelial damage associated with viral infection in COVID-19 suggest that those patients who survive more severe COVID-19 may face prolonged liver repair and accordingly should be followed regularly in the post-COVID period.

Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections.

Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.

Rare abdominal bleeding from the branches of the splenic vein during pregnancy / Ritka hasuri vérzés a vena lienalis ágrendszerébol várandósság alatt.

Összefoglaló. Az "akut has", mint kórkép, a várandósság során mind diagnosztikailag, mind terápiásan nagy kihívást jelent a szülész számára a megváltozott anatómiai viszonyok és a képalkotó eljárások korlátozott használhatósága miatt. Közleményünkben bemutatjuk egy harmadik trimeszterbeli gravida hasi vérömlenyének az esetét, melynek vérzésforrása irodalmi ritkaság, a vérzés típusát a felkeresheto irodalomban még nem írták le terheseknél. Az esettanulmány megírása a páciens orvosi dokumentációi és az ellátásában résztvevo klinikusok, patológusok leletei és beszámolói alapján történt. A várandósságának 33. hetében járó gravida akut hasi tünetegyüttessel jelentkezett klinikánkon, anamnézisébol trauma kizárható volt. Az anya romló kardiorespiratorikus állapota miatt sürgosségi császármetszéssel élo, koraszülött magzatot segítettünk világra. A mutét során kb. 1500 ml vért találtunk a hasüregben, melynek okát általános sebész bevonásával kerestük. Aktív vérzésforrásként a lép ereinek területérol vénás jellegu szivárgó vérzést találtunk, ezért splenectomia mellett döntöttünk. Az eltávolított szervkomplexum teljes szövettani feldolgozása helyenként a kisebb léphilusi vénaágak izomfalának felrostozódását és fokozatos eltunését igazolta, a patológus a vérzés okát a meggyengült érfal endothelen keresztüli vérszivárgásának véleményezte, definitív érfalszakadásra utaló elváltozás nem volt azonosítható. A haemoperitoneum várandósság alatt kifejezetten ritka kórkép, azonban mortalitása mind az anyára, mind a magzatra nézve rendkívül magas. Irodalmi adatok alapján a vérzésforrás leggyakrabban a kismedencei szervek területén jelentkezik. Ritkán a lépartéria aneurysmájának rupturája is elofordul terhességben, a lépvénás eredetu vérzés viszont irodalmi ritkaságnak számít, és az összes feldolgozott és közölt esetben az ér szakadásos sérülése volt a fo ok, az esetünkben leírt, ismeretlen etiológiájú, érfalvesztéses hemorrhágiát sehol nem említik. A várandósunk ellátásánál ellátásánál kulcsfontosságú volt a gyorsan elvégzett exploratív laparotomia, mely a kórkép okát felderítette és megszüntette, lehetové téve az anya és gyermeke túlélését és felépülését. Esetünk rámutat arra, hogy a várandóssági hasuri vérömlenyek kóroktana akár irodalmi ritkaságokat is rejthet, azaz a pontos ok kiderítésével, lumenes vérzésforrás keresésével nem szabad szükségtelen idot veszteni az édesanya és gyermeke életmento ellátásának rovására. Orv Hetil. 2022; 163(8): 328-332. Summary. Acute abdomen during pregnancy is a major challenge for physicians, due to the altered anatomical conditions and the limited use of medical imaging. We present a pregnant woman with a rare form of abdominal bleeding. This case study is based on the patient's medical documentations and interviews with her physicians. A woman in the 33rd week of her pregnancy was admitted to our department with acute abdomen, trauma was ruled out. Due to the deteriorating cardiorespiratory status we performed an emergency caesarean section delivering a living premature newborn. A general surgeon was present, and 1500 ml of blood was evacuated from the abdomen. Active venous type bleeding was present from the splenic vessels, therefore we performed a splenectomy. The histopathological analysis of the whole organ complex showed that the media layer segmentally and progressively disappeared in the splenic hilar veins, giving rise to the high probability that the bleeding was caused by a diathesis-type leakage through the endothelium and to the weakened media layer in the absence of a luminal-type vessel rupture. Hemoperitoneum during pregnancy is an exceptionally rare condition, however its mortality rate is high both for the mother and the fetus. The bleeding usually originates from the pelvis. On rare occasions the bleeding occurs from the splenic vessels although most of them are arterial bleedings from an aneurysm.In our case the emergency laparotomy was essential for the correct diagnosis and the treatment, which resulted in saving and recovering both the mother and the fetus. Orv Hetil. 2022; 163(8): 328-332.

A COVID-19-association-dependent categorization of death causes in 100 autopsy cases.

From March through December 2020, 100 autopsies were performed (Semmelweis University, Budapest, Hungary), with chart review, of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrated by real-time reverse-transcription polymerase chain reaction testing (mean age, 74.73 years, range 40-102 years; 50 males, mean age 71.96 years, and 50 females, mean age 77.5 years). Classified by the date of death, 21 cases were from the pandemic's "first wave" (March through July) and 79 from the "second wave" (August through December). Three mortality categories were defined by relevance of SARS-CoV-2 infection: (1) "strong" association (n=57), in which COVID-19 was primary responsible for death; (2) "contributive" association (n=27), in which a pre-existing condition independent of COVID-19 was primary responsible for death, albeit with substantial COVID-19 co-morbidity; (3) "weak" association (n=16), in which COVID-19 was minimally or not at all responsible for death. Distributions among categories differed between the first wave, in which the "contributive" association cases dominated (strong: 24%, contributive: 48%, weak: 28%), and the second wave, in which the "strong" association cases dominated (strong: 66%, contributive: 21%, weak: 13%). Charted co-morbidities included hypertension (85 %), cardiovascular diseases (71 %), diabetes (40 %), cerebrovascular diseases (31 %), chronic respiratory diseases (30 %), malignant tumors (20 %), renal diseases (19 %), diseases of the central nervous system (15 %), and liver diseases (6 %). Autopsy evaluation analyzed alterations on macroscopy as well as findings on microscopy of scanned and scored sections of formalin-fixed, paraffin-embedded tissue samples (50-80 blocks/case). Severity of histological abnormalities in the lung differed significantly between "strong" and "contributive" (p<0.0001) and between "strong" and "weak" categories (p<0.0001). Abnormalities included diffuse alveolar damage, macrophage infiltration, and vascular and alveolar fibrin aggregates (lung), with macro- and microvascular thrombi and thromboemboli (lung, kidney, liver). In conclusion, autopsies clarified in what extent COVID-19 was responsible for death, demonstrated the pathological background of clinical signs and symptoms, and identified organ alterations that led to the death. Clinicopathologic correlation, with conference discussions of severity of co-morbidities and of direct pathological signs of disease, permitted accurate categorization of cause of death and COVID-19 association as "strong," "contributive," or "weak." Lung involvement, with reduced ventilatory capacity, was the primary cause of death in the "strong" and "contributive" categories. Shifts in distribution among categories, with "strong" association between COVID-19 and death dominating in the second wave, may reflect improved clinical management of COVID-19 as expertise grew.

The diagnosis, morphological particularities, and surgical technique in a case of intravascular leiomyoma extended to the right heart chambers.

Intravenous leiomyoma is a benign smooth muscle cell tumor of uterine origin that may grow into the pelvic veins and the inferior vena cava. It usually affects premenopausal women and the majority (90%) are parous. Because cardiac involvement is present in up to 10% of cases, it may be misdiagnosed as a primary cardiac tumor or a venous thrombus-in-transit. We describe a case of intravascular leiomyomatosis with cardiac extension and the morphological particularities of the removed tumor.

Pigmented papillary carcinoma: a rare tumor of the male breast.

Primary melanin pigment containing tumors of the breast are rare. We report a pigmented papillary carcinoma of a 60-year-old male patient who presented a firm mass 1.7 cm in diameter with an ill defined border on ultrasonography behind the mamilla. To the best of our knowledge this is the third case report of this type of tumor in male breast.

[Removal of sessile recidive rectal polyp with endoscopic submucosal dissection. Case report and review of the literature]. / Sessilis recidív rectumpolip miatt végzett endoszkópos submucosus dissectio.Esetismertetés és irodalmi áttekintés.

UNLABELLED: With the development of flexible endoscopy, removal of the large sessile polyps and superficial malignant tumors that do not exceed the layer muscular mucosa has become today's major challenge. Earlier in various types of mucosectomy performed with such indication it was difficult to control the depth and the lateral margin of the resection surface. Tumors larger than 20 mm could only be removed with the application of the piecemeal technique. PATIENT AND METHOD: 64-year-old female patient's large sessile polyp had been removed earlier with piecemeal technique followed by mucosectomy. On the area of these interventions a recidiv adenoma was found and for this reason endoscopic submucosal dissection was applied. RESULT: The procedure took 55 minutes, and only small volume of bleeding was detected during the intervention. The postoperative period was uneventful, one day later the patient left the hospital. Vertical and lateral resection surface were free of tumor histologically. CONCLUSION: The endoscopic submucosal dissection is suitable for the removal of the large sessile polyp, which could not be successfully removed with earlier techniques.

[Crohn's disease of the duodenum. Clinical signs, diagnosis, conservative and surgical treatment]. / A duodenum Crohn-betegsége, klinikai jelek, diagnosztika, gyógyszeres és sebészi kezelés.

UNLABELLED: Duodenal localization of Crohn's disease is rare, accounting for only 0.5-4% of all cases. Most common complaints are gastric outlet obstruction and weight loss. Histologic findings of endoscopic biopsy are frequently not definitive, making differentiation from other, benign structures complicated. There are also no standard guidelines regarding indications for surgical management. PATIENTS AND METHODS: We reviewed the cases of three surgically managed patients with duodenal Crohn's disease at the 1st Department of Surgery, Semmelweis University of Medicine, Budapest, during a 5-year period (2002-2007). All three patients had persistent symptoms of stomach emptying disorder despite medical therapy and had severe weight loss (13-30 kg). In two cases resection of the stenotic duodenum was performed successfully using Billroth II method. Gastro-jejunal bypass was performed in one case, where the descendent duodenum was inflamed. RESULTS: All patients have been asymptomatic since surgery (9-45 months of follow-up) and recovered their earlier bodyweight. The postoperative period was uneventful. CONCLUSIONS: There is indication of surgery in cases of stenosing duodenal Crohn's disease, when medical therapy is not successful, but long-standing malnutrition should be treated preoperatively. We found perioperative morbidity to be similar in patients with duodenal Crohn's and in those with Crohn's disease of other intestinal locations.

[Investigation of prostate specific antigen in the first decade of its use, in our clinic (1994-2004)]. / A prosztataspecifikus antigén-vizsgálat elso évtizede klinikánkon (1994-2004).

INTRODUCTION AND AIMS: Prostate cancer is the most common malignant tumor in male; its diagnostic algorithm and therapy were investigated. The goal of the study was to compare the data from the first year of clinical use of prostate specific antigen (1994) and the data of 2004. RESULTS: During the first decade, the number of prostate biopsies has increased 4.5-fold times. In 1994, 36.2%, while in 2004, 47.5% of the biopsies demonstrated cancer. The average age of the patients, who underwent biopsy, decreased from 69.7 to 62.3 years; however, the average age of patients who suffered from prostate cancer remained constant (70.8 vs. 71.3 years old). CONCLUSION: In 2004, along with the earlier used PSA level, the free-PSA and PSA-density was also involved in the diagnostic algorithm. The prostate biopsy is guided by a transrectal US, in contrast to the earlier used blind or transperineal method. Consequently, the effectiveness of the prostate biopsy has improved, but the earlier diagnosis and identification are not assured. The Gleason score of the diagnosed prostate cancer was lower; therefore, more patients were selected for curative surgery. The increased average PSA level reflected a higher number of patients at an advanced stage, which could only be treated palliatively.

Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases.

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy.

Detection of Chlamydia pneumoniae in liver transplant patients with chronic allograft rejection.

BACKGROUND: Chlamydia pneumoniae is one of the possible pathogenetic factors of atherosclerotic processes. Foam cell arteriopathy is a generally accepted pathologic feature of chronic liver allograft rejection and has several similarities to the early lesions of atherosclerosis. The aim of the authors' study was to show any existing correlation between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers with chronic rejection. METHODS: Ten liver samples from patients with chronic liver rejection including foam cell arteriopathy and 10 liver samples from healthy individuals were analyzed for the presence of Chlamydia pneumoniae by specific immunohistochemistry and polymerase chain reaction (PCR). Liver samples from two transplant patients with chronic liver rejection without any evidence of foam cell arteriopathy and nine patients with acute liver allograft rejection were also investigated by PCR. RESULTS: In all 10 rejected liver samples, Chlamydia pneumoniae was detected by PCR, whereas only one of the healthy control samples and one of the samples with acute rejection were found to be positive. Immunohistochemistry showed similar results. The positive signals of Chlamydia pneumoniae were localized mainly in the hepatocytes, sinusoidal and perisinusoidal cells, and the cells of portal tracts, whereas most of the altered hepatic arteries showed no or very weak positivity. CONCLUSIONS: The results strongly suggest an association between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers.