Outcomes of Patients with Pulmonary Large Cell Neuroendocrine Carcinoma in I-IV Stage.

Background and Objectives: Large cell neuroendocrine cancer is characterised by poor prognosis. The standard of treatment is still not established. The aim of this study was to assess the predictive factors of overall survival (OS) and progression-free survival (PFS) of pulmonary large cell neuroendocrine carcinoma (LCNEC) and combined LCNEC. Materials and Methods: All patients had confirmed pathology stage I-IV disease recorded between period 2002-2018. Survival curves were estimated by Kaplan-Meier method. Uni- and multivariable analysis was conducted using Cox-regression analysis. Results: A total of 132 patients with LCNEC and combined LCNEC were included. Half of them had clinical stage IIIB/C-IV. Patients were treated with radical (n = 67, including surgery alone; resection with neo-adjuvant or adjuvant chemotherapy, radiochemotherapy, or adjuvant radiotherapy; patients treated with radiochemotherapy alone), palliative (n = 41) or symptomatic (n = 24) intention. Seventeen patients were treated with resection margin R1 or R2. Non-small cell carcinoma (NSCLC) chemotherapy (platinum-vinorelbine; PN schedule) and small-cell lung carcinoma (SCLC) chemotherapy approaches (platinum/carboplatinum-etoposide; PE/KE schedule) were administered in 20 and in 55 patients, respectively. The median (95% Confidence Interval (CI)) OS and PFS were 17 months (9.0-36.2 months) and 7 months (3.0-15.0 months), respectively. Patients treated with negative resection margin, with lower clinical stage, without lymph node metastasis, and with size of primary tumour ≤4 cm showed significantly better OS and PFS. The main risk factors with an adverse effect on survival were advanced CS and positive resection margin. Conclusions: Patients with LCNEC characterized poor prognosis. Independent prognostic factors influencing PFS were initial clinical stage and resection margin R0 vs. R1-2.

Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C.

BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.

Fibrin glue with gentamicin as an alternative to conventional surgery in experimental treatment of duodenal fistula in rats.

Duodenal fistula is a significant ongoing surgical problem. Minimal invasive treatment might be an alternative to conventional open surgery. This study aimed to investigate whether addition of gentamicin to fibrin adhesive can augment current surgical methods. Having established a fistula, the defect was closed using the following: simple suturing, suturing covered with fibrin sealant only, or suturing with fibrin sealant mixed with gentamicin. Bursting pressure and macroscopic and microscopic examination were evaluated on the second and sixth day after surgery. The study demonstrated there was no significant difference in overall outcome between the 3 groups. However, on macroscopic examination, the mixture of antibiotic and fibrin adhesive decreased formation of adhesions and abscesses. Microscopically, there was decreased inflammation, improved granulation, and earlier onset of fibrin filament deposition, possibly leading to enhanced wound healing. The addition of gentamicin to fibrin sealant can be a useful adjunct to standard surgical closure in duodenal fistula management.

Analysis of PI3K/AKT/mTOR signalling pathway in high risk neuroblastic tumours.

Neuroblastoma (NB) represents one of the most common paediatric tumours. Despite advance in NB research and treatment, the outcome of the patients from the high-risk group remains poor. PI3K/AKT/mTOR signalling pathway which is involved in oncogenesis and cancer progression of many tumours, in parallel constitutes the target for the biologically based oncological therapy. In this study we analyzed the status of PI3K/AKT/mTOR signalling route in the primary tumour tissue samples from a group of 39 high-risk NB. The pathway activation state was assessed immunohistochemically using antibodies with specificity towards PI3Kp85, PI3Kp110, phospho-AKT, phospho-mTOR, phospho-p70S6K and phospho-4EBP1. Moreover, expression of PTEN, bcl2 and cyclin D1 was examined. We found that most of tumours were positive for PI3Kp85 and PI3Kp110, as well as for p-AKT, p-mTOR and its downstream effectors p-p70S6K and p-4EBPI. PTEN was expressed in all cases, bcl2 and cyclin D1 staining was found in more than 90% of examined NB. Statistical analysis revealed that p-AKT expression was correlated with p-mTOR and strong cyclin D1 labelling. Furthermore, high expression of p-4EBP1 was significantly associated with p-p70S6K expression, high cyclin D1 and lower differentiation of the tumour. PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk NB and it seems that this group of patients may benefit from targeted therapy with kinase inhibitors.

Outcomes of Patients with Clinical Stage I-IIIA Large-Cell Neuroendocrine Lung Cancer Treated with Resection.

Large-cell neuroendocrine carcinoma (LCNEC) is a rare malignancy with poor prognosis. The rationale of the study was to determine the survival of LCNEC patients in I-IIIA clinical stages who underwent resection. A total of 53 LCNEC (89%) and combined LCNEC (11%) patients in stages I-IIIA who underwent surgery with radical intent between 2002-2018 were included in the current study. Overall survival (OS) and time to recurrence (TTR) were estimated. Uni- and multivariable analyses were conducted using Cox-regression model. Patients were treated with surgery alone (51%), surgery with radiochemotherapy (4%), with radiotherapy (2%), with adjuvant chemotherapy (41%), or with neoadjuvant chemotherapy (2%). The median (95% Confidence Interval (CI)) OS and TTR was 52 months (20.1-102.1 months) and 20 months (7.0-75.6 months), respectively. Patients treated in clinical stage I showed better OS than patients in stages II-IIIA (p = 0.008). Patients with R0 resection margin (negative margin, no tumor at the margin) and without lymph node metastasis had significantly better TTR. In the multivariate analysis, age was an independent factor influencing OS. Recurrence within 1 year was noted in more than half cases of LCNEC. R0 resection margin and N0 status (no lymph node metastasis) were factors improving TTR. Age >64 years was observed as a main independent factor influencing OS.

Identification of high-risk stage II colorectal tumors by combined analysis of the NDRG1 gene expression and the depth of tumor invasion.

BACKGROUND: Experiments on cancer cell lines and animal models indicated that alteration in expression of N-myc down-regulated gene 1 (NDRG1) is associated with development of colon cancer. However, few clinical data are available to assess the role of NDRG1 in progression of human colorectal cancer. This study was undertaken to reveal the prognostic and predictive usefulness of NDRG1 expression determination in colorectal cancer. METHODS: The expression of NDRG1 mRNA was investigated in 108 colorectal cancer tissues by real-time polymerase chain reaction. The level of NDRG1 protein was investigated by immunohistochemistry. RESULTS: Patients with lowered level of NDRG1 mRNA had a statistically significantly shorter 5-year survival rate compared with patients with unchanged expression of NDRG1 (P = .01). The overall survival time for patients with II tumor, node, metastasis system (TNM) stage disease and tumors displaying reduced expression of NDRG1 was significantly shorter compared with patients with preserved NDRG1 expression (P = .024). Moreover, the survival rate of patients with TNM stage II disease and T4 lesion was significantly lower (P = .0005) for patients with reduced level of NDRG1 expression compared with patients with unchanged NDRG1 expression. The stepwise multivariate regression analysis revealed that advanced TNM stage and lowered NDRG1 expression level were independent unfavorable prognostic factors for patient survival. CONCLUSIONS: The assessment of NDRG1 expression offers valuable prognostic information for patients with colorectal cancer, especially for those with stage II disease. We propose that NDRG1 expression level could be used to select patients with stage II disease who are at increased risk of unfavorable outcome, and who may benefit from adjuvant therapy.

High glucose suppresses expression of equilibrative nucleoside transporter 1 (ENT1) in rat cardiac fibroblasts through a mechanism dependent on PKC-zeta and MAP kinases.

Recently it was demonstrated that the elevated concentration of glucose but not lack of insulin is responsible for suppression of equilibrative nucleoside transporter (ENT1) in diabetic rat cardiac fibroblasts (CFs). The present study was undertaken to determine the signaling pathway utilized by glucose to regulate the expression of ENT1 in the primary culture of rat CFs. Pretreatment of CFs with Go 6983, an isozyme non-selective PKC inhibitor, prevented the high glucose (25 mM) effect on ENT1 mRNA level and nitrobenzylthioinosine (NBTI)-sensitive adenosine uptake. Similar effect was observed with a cell-permeable PKC-zeta pseudosubstrate, whereas Go 6976 a selective inhibitor of Ca(2+)-dependent PKC-alpha and PKC-beta isozymes had little effect on high glucose-induced suppression of ENT1 mRNA level. Incubation of CFs with nitric oxide (NO) donors (SNAPE, SNP) or NO synthase inhibitors (L-NAME, L-NMMA) prior to exposition of CFs to high glucose did not change the glucose effect on ENT1 mRNA level. The high glucose-induced suppression of ENT1 expression was blocked by PD9859 (an inhibitor of MEK), whereas neither wortmannin (an inhibitor of PI3K) nor rapamycin (an inhibitor of mTOR) affected the glucose action on ENT1 transcript level. Highly effective in preventing the high glucose effect on ENT1 mRNA level were GW 5074 (an inhibitor of Raf kinase) and SB 203580 (selective p38 MAPK inhibitor). These findings indicate that high glucose suppresses the expression of ENT1 in CFs by NO independent manner involving the signaling through PKC-zeta, Raf-1, MEK, and p38 MAPK pathways.

The possible role of factor H in colon cancer resistance to complement attack.

A soluble complement inhibitor factor H (FH) and its splice variant factor H-like protein (FHL) have been recently discovered to play a major role in malignant cell escape from complement-mediated cytotoxicity in lung-, ovarian- and glia-derived neoplasms. The role of FH in colon cancer has not yet been examined. Here, we studied immunocytochemically FH/FHL expression in tumor samples derived from 40 patients, with both primary colon adenocarcinoma and metastatic foci in the liver. FH/FHL immunoreactivity was present in stroma of both primary and metastatic tumors, in virtually all patients. The cellular immunoreactivity was observed infrequently. Importantly, when analyzed quantitatively, FH/FHL immunoreactivity was significantly increased in liver metastases when compared with the primary sites. In addition, we have analyzed FH and FHL expression in 5 colon cancer cell lines: SW480, SW620, HCT116, HT-29 and Lovo. FH mRNA and FH secretion were observed in SW620 and HT-29 cells, whereas FHL was produced only by HT-29 cell-line. By confocal and electron microscopy, FH immunoreactivity was associated with the plasma membrane and intracellular vesicular structures. Finally, we have analyzed the role of FH in the susceptibility of SW620 colon cancer cells to complement-mediated damage. When FH function was blocked, using specific antibody, the cells became more susceptible to lysis. Taken together, our results suggest an important role of FH/FHL in colon cancer cells defense against complement-mediated cytotoxicity, and in metastatic process.

Clinicopathological considerations on angiogenic potential in neuroblastoma Schwannian stroma - poor tumours.

The aim of the study was to determine microscopic angiogenic parameters of neuroblastoma (NB) Schwannian stroma-poor tumours. Furthermore the associations between vascular parameters and clinicopathological features of tumours and basic prognostic factors were analysed. Examined tissue samples from 62 NB came from 39 untreated and 23 chemotherapy pretreated tumours. The clinicopathological data comprised: patients' age, gender, survival, tumour site and stage, tumour histology and MYCN status.The morphological analysis of the angiogenic potential concentrated on examination of vascular patterns - classical type or pathological angiogenesis with mural microvascular proliferation (MVP). The quantitative study included semi-automatic assessment of vascular density (VD) in CD34 stained tumour sections. Pathologic angiogenesis with MVP, including simple and/or glomeruloid type, was encountered in 25 cases and was more frequent in differentiating histology subtype and extraadrenal tumours. VD value ranged from 56 to 385 vessels/mm2 (median 149). Higher VD was connected with younger patient's age. In untreated tumours VD was significantly higher in infants than in children over one year of age. Pathologic type angiogenesis and lower VD were found to be associated with shorter survival. Our study confirmed high vascularization of NB and revealed common occurrence of vascular pattern with MVP. Angiogenic potential in the analysed group showed diversity related to some clinicopathological tumour features. This points toward heterogeneity of NB tumours in vascular aspects, possibly affecting tumours' reactivity to antiangiogenic therapy.

[Carcinoma ex pleomorphic adenoma of major salivary glands--a clinicopathologic review]. / Rak w gruczolaku wielopostaciowym duzych gruczolów slinowych--analiza kliniczno-patologiczna.

BACKGROUND: Pleomorphic adenoma (PA) is the most common neoplasm of the major salivary glands. There are three subtypes of malignant PA: carcinoma ex pleomorphic adenoma (CXPA); carcinosarcoma (true malignant mixed tumor) and metastasizing pleomorphic adenoma. The most common subtype of malignant PA is CXPA which develops in primary or recurrent PA. For proper diagnosis of CXPA, a statement of coexistence of pleomorphic adenoma and carcinoma (or carcinoma after prior PA surgery) is needed. Own material is presented because of rarity and clinicopathologic specificity of this neoplasm. METHODS: Retrospective analysis of the medical data of 19 patients who were treated at our department because of CXPA from 1990 to 2002 was done. The following clinical factors were evaluated: age, sex, symptoms (time of lasting, evolution), tumor size, invasion of the adjacent structures and facial nerve, neck nodes, clinical stage, treatment outcome. One pathologist reviewed histological material of 18 out of 19 patients who had been operated and pathological factors such as sensitivity and accuracy of fine needle aspiration biopsy, grade, histology and proportion of malignant component in tumor, lymph nodes metastases were analyzed. RESULTS: There were 11 men and 8 women, the mean age was 57 years. In 15 cases, tumor was localized in the parotid and in 4 in the submandibular gland. Two patients had history of prior surgery of PA. Duration of symptoms of benign PA was from 2 to 40 years (mean 17.8 years). Symptoms of malignant transformation occurred in 15 patients, the most common were rapid enlargement of tumor, pain and facial nerve palsy. Tumor size varied from 2 to 20 cm with a mean of 6 cm. In 14 patients, the neck was evaluated clinically as No, in 5, examination identified enlarged lymph nodes. Adjacent structures were invaded by neoplasm in 5 cases. Sensitivity and accuracy of fine needle aspiration biopsy in detection of malignant character of PA were 60% and 46% respectively. 17 out of 18 tumors reviewed by the pathologist were high grade. Only in 6 patients, proportion of carcinoma in the mass was less than 50%. The most common malignant component in CXPA was adenocarcinoma (9 cases) and undifferentiated carcinoma (6 cases). Pathologic examination showed metastases to the lymph nodes in 7 out of 10 patients with prior neck dissection. 16 patients were treated surgically (12 of them had also radiation therapy) and 3 patients underwent only (chemo)radiotherapy. Determinate survival at 5 years was 73.6% and in the group treated surgically (alone or with postoperative irradiation) 87.5%. CONCLUSIONS: Malignant transformation of PA occurs in 5 to 25% untreated patients, usually after 15-20 years and warning symptoms are present in the most cases. Fine needle aspiration biopsy has insufficient sensibility and accuracy in detection of malignant character of PA. Clinical picture and histopathological examination determinate the diagnosis of CXPA. Proper histological classification of malignant component can be found difficult. Surgical treatment (alone or with postoperative irradiation), if possible, allows to achieve good locoregional control of CXPA. 5-years survival varied between 30 to 76%. The best method of prevention and treatment of CXPA is early and radical removal of all major salivary glands tumors.

[Noninvasive fungal sinusitis (fungus ball)--diagnostic difficulties]. / Nieinwazyjne grzybicze zapalenie zatoki (grzybniak)--trudnosci diagnostyczne.

Noninvasive fungal sinusitis (fungus ball) is usually found in one sinus and the most frequently is caused by Aspergillus. Diagnostic criteria are based on histopathology, and fungal cultures are frequently negative. The clinical symptomatology mimics chronic rhinosinusitis and radiology, specially CT and MRI are helpful for making decision of surgery. The authors present 4 cases of fungus ball of the paranasal sinus. In one case clinical symptoms, endoscopic examination of nasal cavity and CT scans suggested foreign body in the maxillary sinus. In other case clinical and radiological evidences made us to thing of neoplasmatic disease of the frontal sinus. In remaining two cases mycetoma was found in the sphenoid sinus. Surgical removal was the treatment in all cases and followed by systemic antifungal therapy in one case because of bone destruction. Histopathology revealed hyphae of Aspergillus without evidence of tissue invasion, fungal cultures in two cases were negative, an in other two Aspergillus fumigatus culture were obtained.

VEGF, Flt-1, and microvessel density in primary tumors as predictive factors of colorectal cancer prognosis.

Angiogenesis in the primary tumor is known to be necessary for tumor progression in adenocarcinomas of the colon. However, whether angiogenesis in the primary tumors of patients with colorectal cancer affects their prognosis has yet to be fully elucidated. The aim of the present study was to assess the association between selected pathoclinical parameters and overall survival of resectable colorectal cancer patients with the expression of angiogenesis-promoting factors, including vascular endothelial growth factor (VEGF) and Fms-like tyrosine kinase receptor (Flt-1), and microvessel density (MVD) in the primary tumor. VEGF and Flt-1 expression were assessed, as well as MVD (with anti-CD34) by immunohistochemistry in 139 archived primary colorectal cancer tissue samples. These results were compared with the overall survival of the patients and potential prognostic pathoclinical parameters. A higher MVD in the tumors expressing Flt-1 (P=0.04) was identified. However, there was no correlation between the pathoclinical parameters of colon cancer and Flt-1 expression, VEGF expression, or MVD in the tumor. Furthermore, the intensity of VEGF expression, Flt-1 expression and tumor MVD did not correlate with the overall survival of the patients. Therefore, although increased expression of VEGF and Flt-1 was correlated with an increased expression of MVD in the primary tumors of resectable colorectal cancer patients, these factors were not correlated with prognostic pathoclinical factors and overall survival.

Cerebellopontine angle tumours: radiologic-pathologic correlation and diagnostic difficulties.

A group of 119 cases of cerebellopontine angle (CPA) tumours was studied looking at the pathological composition, relative incidence of tumour types, their radiological features and the pathological-radiological correlations. Tumours with preoperative radiological diagnosis and verified pathologically were analyzed. Histopathologically the material consisted of 77 schwannomas and 42 non-acoustic tumours. Radiological retrospective evaluation of CT and/or MRI documentation was performed in 84 patients. The tumours were classified according to Koos's staging scale. Diagnostic discrepancies (histopathological vs radiological) according to the clinical stage of CPA tumours were analyzed. In our series non-acoustic tumours made up 37% of CPA lesions. Sharp tumour-pyramis angle and intracanalicular fraction are not exclusive features of schwannomas. Tumours in stage IV are the most heterogeneous and diagnostically difficult group.

Pregranulomatous phase of sarcoidosis: immunohistochemical diagnosis.

Histopathological confirmation of clinical suspicion of sarcoidosis is based on the finding of non-caseating granulomas in biopsy material, usually in prescalene lymph nodes or in transbronchial lung biopsies. Lymph node reactive sinus histiocytosis (RSH) seen in relation to various inflammatory and non-inflammatory diseases can mimic the pregranulomatous phase of sarcoidosis (PSH). Differentiation of sinus histiocytosis based on histopathological features alone is limited. The purpose of this study is immunohistochemical determination of lymph node cellular response in granulomatous sarcoidosis, the PSH and RSH using a immunohistochemistry employing a panel of antibodies. Patient groups under study each contained 25 patients and included: those with clinical picture of sarcoidosis and non-caseating granulomatous lymphadenitis; those with confirmed sarcoidosis and with sinus histiocytosis without granuloma formation in lymph nodes; and finally, those without sarcoidosis and with "reactive" sinus histiocytosis in lymph nodes. Lymph node biopsy tissue was fixed in buffered formaldehyde, routinely processed to paraffin wax blocks, cut into 4-microm-thick sections, stained with hematoxylin and eosin and immunohistochemically labelled using a triple-layer APAAP protocol with purified polyclonal antibodies directed against SP 70 and SP90 from Mycobacterium tuberculosis and monoclonal antibodies against CD22, CD4, CD8, CD56, and CD68. Intensity of immunolabelling was assessed semiquantitatively by two independent observers. An increased CD4:CD8 ratio, moderate increase of immunolabelling for CD68 and slight decrease in immunolabelling for CD20, CD56, and SP90 was indicative of PSH when compared with RSH. The most notable difference between the studied groups was a difference in immunoreactivity to SP70 and CD4 antibodies. Lymph nodes with pregranulomatous sinus histiocytosis labelled with both antibodies. This profile of immunolabelling can be used in the differentiation of this condition from reactive sinusoidal lesions.

Neutrophil engagement and septic challenge in acute experimental pancreatitis in rats.

AIM: To investigate the influence of neutrophil adhesion molecule blockade with monoclonal antibody (MoAb CD11b) and E. coli lipopolysaccharide (LPS) administration on experimental acute pancreatitis (AP). METHODS: AP was induced by four ip injections of cerulein (Cn) at 1-h intervals. MoAb CD 11b and LPS were administered at the beginning of the experiment. RESULTS: The neutrophil count and chemiluminescence were diminished at the beginning of AP. The oxidative stress parameters were found within the pancreatic gland. MoAb CD 11b used for AP resulted in a significant reduction of pancreatic infiltration and pancreatitis oxidative stress parameters. Serum interleukin-6 (IL-6) was not detected in AP animals, whereas high serum IL-6 concentration was noted only in animals receiving LPS. CONCLUSION: Neutrophils are involved in pancreatic damage in the early stage of AP. Neutrophil infiltration reduction protects the pancreatic gland from destruction during AP. LPS does not change the early course of Cn pancreatitis in rats.

Microvascular density in chronic pancreatitis and pancreatic ductal adenocarcinoma.

Chronic pancreatitis and pancreatic adenocarcinoma represent two pathologic phenomena with marked production of connective tissue stroma containing numerous small blood vessels. The aim of this study was to characterise quantitatively the vascular supply of pancreatic adenocarcinoma and fragments of the periductal tissue collected from patients with chronic pancreatitis. The study material included 18 cases of pancreatitis and 22 cases of pancreatic ductal adenocarcinoma. Microvessels were marked using monoclonal anti-CD34 antibodies. The number of blood vessels in the fibrous stroma was significantly higher in the chronic pancreatitis samples compared to the pancreatic carcinoma group (mean vessel count 298 and 194 vessel/mm2; median 251 and 187 vessel/mm2 respectively; p<0.01). Distributions of the vascular diameter in both studied groups were very similar. The obtained results suggest that the development of vascular network accompanying chronic pancreatitis is more effective in some parts of pancreas compared to angiogenic intensity in pancreatic adenocarcinoma.

Angiogenesis in glioblastoma--analysis of intensity and relations to chosen clinical data.

Microvascular proliferation (MVP) is one of the histopathological hallmarks of glioblastoma (GB). In this study angiogenic potential in GB was analysed according to the morphology of MVP and by assessment of vascular density. The analysis of relations of vascular parameters to chosen clinical features was performed. Tissue samples from 46 GB cases were examined. The clinical data included: patients' age (32-78 years), gender (17 women, 29 men), location (frontal lobe--13, temporal--18, parietal--14, two lobes--1) and tumour size in CT (2-9 cm). Tumour vascularisation was analysed morphologically and quantitatively. Histologically two types of MVP were distinguished: simple and glomeruloid. In vascular hot spots vessel density was assessed on sections immunostained for vWf. Simple type proliferation was found in all cases. Glomeruloid proliferation was found in 33 cases with mean age of patients 59.5 yrs, while in the group without glomeruloids mean age was 48 yrs (statistically significant difference, p < 0.01). Mean vascular density value in examined GB was 150.4 vessels/mm2 (median 141.5; SD--56.4) and younger age was related to higher vascular density (correlation coefficient R = -0.35; p = 0.017). Vascular parameters were related only to the patients' age among the analysed clinical data. The presented results show that morphologically microvascular proliferation is more intense in older GB patients, since higher vascular density is related to younger age. This observation may suggest the diversity of GB angiogenic potential depending on patients' age.

K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma.

The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival.

Transthoracic lung ultrasonography in pulmonary alveolar proteinosis - case report.

A pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an accumulation of surfactant components in lung alveoli. In diagnosis and monitoring of the disease high resolution computed tomography (HRCT) is usually used. Unfortunately, repeated exposure to CT scanning may be associated with an increased risk of radiation. We present a patient in whom repeated transthoracic lung ultrasonography (TLUS) brought parallel to HRCT data in assessing PAP extent. It may indicate that TLUS might be potentially a relevant tool in monitoring of PAP.

Main histologic types of non-small-cell lung cancer differ in expression of prognosis-related genes.

BACKGROUND: There is increasing evidence that suggests that particular histopathologic types of non-small-cell lung cancer (NSCLC) display distinct molecular characteristics. We analyzed, in lung squamous cell carcinoma (SCC) and adenocarcinoma (AC), the expression of 8 genes that constitute 2 previously reported prognostic expression signatures in NSCLC. METHODS: Fresh-frozen tumor and normal lung samples were obtained at surgery from 135 patients with stage I-III NSCLC (89 (65.9%) SCC, 46 (34.1%) AC). Expression of CSF1 (colony stimulating factor for macrophages), carbonic anhydrase 9 (CA9), epithelial growth factor receptor (EGFR), dual specificity phosphatase 6 (DUSP6), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), monocyte to macrophage differentiation-associated (MMD), lymphocyte-specific protein tyrosine kinase (LCK) and signal transducer and activator of transcription 1 (STAT1) was assessed in SCC, AC, and in normal lung by quantitative reverse transcriptase - polymerase chain reaction (qRT-PCR). Metastasis-free survival was analyzed according to the median value of gene expression in the entire NSCLC cohort and separately in SCC and AC. RESULTS: Expression of CA9, CSF1, DUSP6, STAT1, and MMD differed between NSCLC and normal lung. EGFR was more abundant in SCC compared with AC, whereas the reverse was true for DUSP6 and ERBB3. A high expression of CSF1 correlated with shorter metastasis-free survival in the entire NSCLC group (P = .016) and in SCC (P = .049) and AC (P = .034) cohorts. CONCLUSIONS: Several genes considered prognostic in NSCLC showed significantly different expression in SCC and AC, and thus should be analyzed separately in these 2 subtypes for their prognostic significance. CSF1 is similarly expressed in SCC and AC, and portends a poor outcome in the entire group of patients with NSCLC, and in SCC and AC when considered separately.