Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer.

BACKGROUND: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. METHODS: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive lung cancer patients with brain metastases. RESULTS: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p < 0.001 and p < 0.001, respectively). There was a positive correlation between the size of metastasis and the thickness of peritumoral brain edema (p < 0.001). It was thicker in supratentorial tumors (p = 0.019), in younger patients (≤50 years) (p = 0.042), and in females (p = 0.016). The time to development of brain metastasis was shorter in central than in peripheral lung cancer (5.3 vs. 9.0 months, p = 0.035). Early brain metastasis was characteristic for adenocarcinomas. A total of 135 patients had brain only metastases (N0 disease) characterized by peripheral lung cancer predominance (p < 0.001) and a longer time to development of brain metastasis (9.2 vs. 4.4 months, p < 0.001). OS was longer in the brain only subgroup than in patients with N1-3 diseases (p < 0.001). CONCLUSIONS: The clinicopathological characteristics of lung cancer are related to the development and radiographic features of brain metastases. Our results might be helpful in selecting patients who might benefit from prophylactic cranial irradiation.

[Soft tissue-cutting law, i.e. the career concept of an autopsy assistant]. / Lágyrészbe vágó jog, avagy egy boncmester-életpálya koncepciója.

Practical experience shows that the autopsy assistant society is fairly divided. There are some people who would have needed a thorough basic training, and there are those who - due to their diligence and the close cooperation with physician colleagues - would deserve an opportunity for further progress due to their extensive knowlegde. As regards the autopsy assistant profession the training, and the training system as well has changed significantly, and it requires further changes. Examining the issue in a wide spectrum, the aim of the authors is, as much as possible, to promote the formation of an "Autopsy assistant career," in which they want to create a predictable way for the members of the profession from the phase of becoming a student (competency, training, exams, vocational training, single note) to obtaining the master's degree. The authors would like to provide a summary about their experience and plans regarding this issue.

Role of duties related to COVID-19 suspected, probable and confirmed fatality cases / [Elhunytakkal kapcsolatos teendok COVID­19-gyanús, valószínusített és megerosített esetekben]

The outbreak caused by SARS-CoV-2 beta-coronavirus, first identified in Wuhan, China, was declared a pandemic by the World Health Organization on 11th March, 2020. In Hungary, the first confirmed COVID-19 case was reported on 4th March, 2020, and on 15th March, the first fatality related to the infection was announced. At the moment of the latter event, there was no central, standardized guideline, which could explain the necessary precautions, and provide an unequivocal description on how to handle the dead body. The procedure of transportation, storage, occurent autopsy or final disposition of the deceased raise a lot of questions, especially on how to carry out these tasks. Legislation related to infectious diseases and decedent management in general do not provide enough information on how to perform duties in a COVID-19 fatality case. The chief medical officer suspended the execution of autopsies, except in cases of unnatural death, since 19th March, however, the transportation and storage of fatalities can still be a problem. The Department of Pathology of the Healthcare Professional College of the Ministry of Human capacities published a procedure on recommended post-mortem duties on 21st March, but the suggested protocols only represent a narrow spectrum of international recommendations. Therefore supplementation may be necessary. Sadly, post-mortem protocols, in spite of their importance, are also underrepresented in the international literature. A further problem, wich makes adoptability difficult, is that available foreign guidelines and algorithms are optimized for different legislation, and organisations, resources not available in our country. In this article, besides providing a summary of literature, we would also like to make practical recommendations which may increase the safety of healthcare providers participating in the treatment or pathological duties with COVID-19 suspected, probable and confirmed cases. Orv Hetil. 2020; 161(17): 713­722.

Distinct claudin expression profile in histologic subtypes of lung cancer.

PURPOSE: Claudins are the main constituents of tight junctions. Little is known about their expression and localization in the normal bronchial epithelium and in lung cancer. PATIENTS AND METHODS: One hundred four lung cancer tissue blocks were studied including 46 adenocarcinomas (ADC), 30 squamous cell carcinomas (SCC), 15 small cell lung cancers (SCLC), 8 typical and 5 atypical carcinoids. All slides contained normal bronchial mucosa as well. Immunohistochemistry using antibodies against claudins-1, -2, -3, -4, and -7 proteins, as well as semi-quantitative estimation were performed. RT-PCR analysis was also carried out in 22 immunohistochemically representative tumor samples. RESULTS: Normal bronchial epithelial cells expressed all the examined claudin proteins. When compared, SCLCs and carcinoids showed striking differences in regard to claudins-1, -3, and -4 expressions (p<0.0001, p<0.0001, and p<0.0004, respectively), whereas ADCs and SCCs revealed significant differences in claudins-3, -4, and -7 expressions (p<0.0001, p<0.0001, and p<0.0053, respectively). However, comparison of ADCs with SCLCs revealed significant difference only in claudin-2 expression (p<0.0002). The comparison of ADCs and carcinoids resulted in significant differences regarding claudins-1, -3, and -4 expressions (p<0.0006, p<0.0001, and p<0.0001, respectively). SCCs and SCLCs varied in respect to claudin-2, -3, and -4 expressions (p<0.0009, p<0.0001, and p<0.0019, respectively), whereas SCCs and carcinoids showed different claudins-1 and -4 expressions (p<0.0076 and p<0.0045, respectively). RT-PCR analysis revealed parallel changes in the mRNA and protein expression of certain claudins. CONCLUSIONS: The observed distinct claudin expression profile within the non-small cell lung cancer group, further, the marked differences between SCLCs and carcinoids may have differential diagnostic impact, and the overexpression of certain claudins might have therapeutic implications.

Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases.

The aim of the study was to investigate the correlation between claudin (CLDN) protein expression and clinicopathological parameters as well as survival in histological subtypes of non-small cell lung cancer. Archived surgical resection specimens of 137 pathologic stage I primary bronchial cancers including 49 adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative estimation (IHC scores 0-5) were performed. Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p = 0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0.001, respectively) and SCC (CLDN1: p < 0.001, CLDN3: p < 0.001, CLDN7: p < 0.001, respectively). Highly significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L-ADC (p < 0.001 in both), which was not observed in SCC (p = 0.131). ADC and SCC showed no correlation with smoking, whereas in case of L-ADC heavier smoking correlated with higher CLDN3 expression (p = 0.020). Regarding claudin expression and survival, in SCC significant correlation could be demonstrated between CLDN1 IHC positivity and better survival (p = 0.038). In NSCLC as a whole, high CLDN2 expression proved to be a better prognostic factor when compared with cases where CLDN2 IHC score was 0-1 vs. 2-5 (p = 0.009), however, when analyzed separately, none of the histological subgroups showed correlation between CLDN2 expression and overall survival. The claudin expression pattern was significantly different not only between the SCC-ADC and SCC-L-ADC but also between the L-ADC and ADC histological subgroups, which strongly underlines that L-ADC represents a distinct entity within the ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but only in the SCC subgroup.

Domain interactions direct misfolding and amyloid formation of yeast phosphoglycerate kinase.

There are proteins that are built of two structural domains and are deposited full-length in amyloid plaques formed in various diseases. In spite of the known differences in the mechanisms of folding of single- and multidomain proteins, no published studies can be found that address the role of the domain-domain interactions during misfolding and amyloid formation. By the discovery of the role of domain-domain interactions, here we provide important insight in the submolecular mechanism of amyloid formation. A model system based on yeast phosphoglycerate kinase was designed. This system includes the wild-type yeast phosphoglycerate kinase and single-tryptophan mutants of the individual N and C terminal domains and the complete protein. Electron microscopic measurements proved that amyloid fibrils grow from all mutants under identical conditions as for the wild-type protein. Misfolding and amyloid formation was followed in stopped-flow and manual mixing experiments on the 1 ms to 4 days timescale. Tryptophan fluorescence was used for selective detection of conformational changes accompanying the formation of the amyloidogenic intermediates and the growth of amyloid fibrils. The interactions between the polypeptide chains of the two domains direct the misfolding process from the early steps to the amyloid formation, and influence the final structure. The kinetics of misfolding is different for the individual domains, pointing to the significance of the amino acid sequence. Misfolding of the domains within the complete protein is synchronized indicating that domain-domain interactions direct the misfolding and amyloid formation mechanism.

Intra and postoperative evaluations of microcirculation and micro-rheological parameters in a rat model of musculocutaneous flap ischemia-reperfusion.

PURPOSE: To examine how the ischemia-reperfusion injury of latissimus dorsi-cutaneous maximus (LDCM) musculocutaneous flap affects the microcirculatory (flap's skin surface) and hemorheological parameters, and whether an intraoperative deterioration would predictively suggest flap failure in the postoperative period. METHODS: Ten healthy male rats were subjected to the study. In Group I the left flap was sutured back after 2-hour, while the contralateral side was right after its elevation. In Group II the same technique was applied, but the pedicle of the left flap was atraumatically clamped for 2-hour. The contralateral side was left intact. On the flap skin surface laser Doppler tissue flowmetry measurements were done before and after and during the protocols applied in the groups. Microcirculatory and hemorheological examinations were done postoperatively. RESULTS: The microcirculatory parameters significantly decreased during immobilization and ischemia. Afterwards, all the regions showed normalization. In the retrospective analysis there was a prominent difference between the microcirculatory parameters of necrotic and survived flap during the early postoperative days (1-3) in Group II. Erythrocyte aggregation and deformability showed only slight differences. CONCLUSIONS: Two-hour ischemia and reperfusion caused deterioration in latissimus dorsi-cutaneous maximus flap microcirculation. Predicting the possible postoperative complication, the intraoperative laser Doppler measurement can be informative.

Silicone oil in the subarachnoidal space--a possible route to the brain?

Using this case report, we sought evidence that silicone oil may infiltrate the subarachnoidal space. Vitrectomy combined with silicone oil implantation was performed on the right eye of a 72-year-old woman. The silicone oil was removed 2 months later, because the patient had developed elevated intraocular pressure. The blind and painful eye was subsequently enucleated. By light microscopy, presumed silicone oil bubbles were identified in the optic nerve and the subarachnoidal space of the enucleated eye. These vacuoles were examined by energy-dispersive X-ray analysis (EDAX). In addition, in the vacuoles, immunohistochemistry was used to test for the presence of CD 68-positive macrophages. Silicone oil infiltration sites in the optic nerve, in the central retinal artery, and in the subarachnoidal space were located by light microscopy and confirmed by EDAX. CD 68-positive macrophages were found in the silicone-filled vacuoles. Silicone oil used for endotamponade may infiltrate the optic nerve and even the subarachnoidal space. This supports the assumption that silicone oil, under special circumstances, may even migrate into the brain.

[Role of osteopontin in the formation of microcalcifications in breast cancer]. / Az osteopontin szerepe a microcalcificatiók kialakulásában emlócarcinomákban.

INTRODUCTION: Osteopontin, a non-collagen, Ca-binding phosphoprotein, plays roles in both physiological and pathological mineralisation processes. Its expression may be severely altered in malignant tumours. AIM: To investigate the presence of this protein in breast tumours showing mammographic microcalcifications. MATERIAL: In this study the authors investigated immunohistochemically the osteopontin expression in 26 breast tumours. The elemental composition of the microcalcifications of the same tumours was also examined with energy dispersive spectrometer linked to a scanning electron microscope. RESULTS: Osteopontin expression was found within the tumours in the tumour cells, in vascular smooth muscle cells, in the myoepithelial cells of the normal ducts, and in macrophages. Extracellular osteopontin positivity was seen around calcified foci. There was no correlation between osteopontin positivity and the examined prognostic factors: grade, type and size of the tumour, axillary lymph nodes status, or age. Two types of microcalcifications were seen: 1. Ca-phosphate only, 2. Those composed of various other elements. CONCLUSION: The presence of osteopontin in the vicinity of calcified foci and in the vessel walls seems to support the hypothesis that osteopontin takes part in calcification process.

[Familial adenomatous polyposis coli--case report]. / A familiaris adenomatosus polyposisról egy eset kapcsán.

The authors report the case of a young 35 year-old male patient, investigated due to thrombocytosis for three years. First the diagnosis of chronic myeloproliferative disease was made. The diagnosis of familial adenomatous polyposis was only evident in advanced stage of the disease. Upper abdominal US, abdominal CT, double-contrast barium enema examination and colonoscopy proved advanced synchronous colorectal cancers (sigmoid and descending colon) with liver metastases along with polyposis throughout the whole large bowel. Days after the diagnosis was made the patients condition deteriorated rapidly and he died with septic symptoms suggesting bowel perforation and pneumonia. Beside the case report the authors try to give a short overview of the current literature of relatively rare but potentially fatal hereditary colon cancer syndromes to awake the attention of the clinicians to investigate more cautiously the background of unexplained clinical-laboratory signs in young adults.

Intra and postoperative evaluations of microcirculation and micro-rheological parameters in a rat model of musculocutaneous flap ischemia-reperfusion

PURPOSE:To examine how the ischemia-reperfusion injury of latissimus dorsi-cutaneous maximus (LDCM) musculocutaneous flap affects the microcirculatory (flap's skin surface) and hemorheological parameters, and whether an intraoperative deterioration would predictively suggest flap failure in the postoperative period.METHODS: Ten healthy male rats were subjected to the study. In Group I the left flap was sutured back after 2-hour, while the contralateral side was right after its elevation. In Group II the same technique was applied, but the pedicle of the left flap was atraumatically clamped for 2-hour. The contralateral side was left intact. On the flap skin surface laser Doppler tissue flowmetry measurements were done before and after and during the protocols applied in the groups. Microcirculatory and hemorheological examinations were done postoperatively.RESULTS: The microcirculatory parameters significantly decreased during immobilization and ischemia. Afterwards, all the regions showed normalization. In the retrospective analysis there was a prominent difference between the microcirculatory parameters of necrotic and survived flap during the early postoperative days (1-3) in Group II. Erythrocyte aggregation and deformability showed only slight differences.CONCLUSIONS: Two-hour ischemia and reperfusion caused deterioration in latissimus dorsi-cutaneous maximus flap microcirculation. Predicting the possible postoperative complication, the intraoperative laser Doppler measurement can be informative.

Chlamydophila pneumoniae and human cytomegalovirus in atherosclerotic carotid plaques--combined presence and possible interactions.

The aim of our study was to investigate the combination of Chlamydophila pneumoniae and human cytomegalovirus (HCMV) as a pathogenic factor in atherosclerosis. Accordingly, we tested by means of PCR and immunohistochemistry the presence of these pathogens in the same atherosclerotic carotid specimen. The histology of the samples and the patients' antibodies against these pathogens were evaluated. Further, we examined the impact of C. pneumoniae and HCMV infection on the gene expression of the human monocytic cell line U937. Six of the 22 samples contained only C. pneumoniae, 4 contained only HCMV, 7 contained both C. pneumoniae DNA and/or antigens of both pathogens, and 5 samples were negative. No correlation was found between the presence of these microbes and either the cellular structure of the plaques, or the serostatus of the patients. The infection of U937 cells with HCMV and especially C. pneumoniae induced inflammation and atherosclerosis-related genes. Furthermore, the doubly-infected cells produced higher levels of the mRNA of pro-platelet basic protein and fatty acid binding protein 4. In conclusion, C. pneumoniae is often present in combination with HCMV in atherosclerotic carotid lesions. The in vitro coinfection model reveals that the doubly-infected monocytes are potent expressors of proatherosclerotic genes, suggesting that this coinfected population may accelerate the process of atherosclerosis.

Role of angiotensin II, sympathetic stimulation and salt in the development of structural vascular changes in rat kidney.

1. Functional and structural vasoconstriction of renal cortical arteries is the earliest change leading to hypertension. In the present study, the interaction of a subpressor dose of angiotensin (Ang) II, a 2% NaCl diet and sympathetic stimulation in the form of overnight cold exposure was investigated in the development of renal structural vascular changes in male Sprague-Dawley rats. 2. Morphometric measurements of renal cortical resistance arteries and volume density measurements of renal cortical components were performed in eight groups of rats after 12 weeks of treatment: AngII; 2% NaCl diet; cold exposure (5 degrees C); AngII plus 2% NaCl diet; AngII plus cold exposure; cold exposure plus 2% NaCl diet; ANG II plus 2% NaCl diet plus cold exposure; and sham operation and treatment (control). 3. The average weekly systolic blood pressure of AngII-treated plus salt-fed rats was increased, whereas that of cold-stressed plus salt-fed rats at room temperature decreased compared with controls. The blood pressure rise of the former group was accompanied by an increased wall-to-lumen ratio (WLR) of cortical resistance arteries and decreased glomerular volume, whereas the reduction in blood pressure in the latter group was accompanied by a decreased WLR of cortical resistance arteries and increased volume density of cortical renal tubules. There were no changes in either the blood pressure or renal structure of the other groups. 4. There is a parallel relationship between changes in preglomerular structural vascular resistance and changes in blood pressure in rats. It remains to be determined whether renal cortical structural changes are the cause of, or are compensatory for, chronic changes in blood pressure.