Texture features of primary tumor on 18F-FDG PET images in non-small cell lung cancer: The relationship between imaging and histopathological parameters. / Características de textura del tumor primario en imágenes de 18F-FDG PET en cáncer de pulmón de células no pequeñas: la relación entre parámetros de imágenes y parámetros histopatológicos.

OBJECTIVES: The aims of this study were to evaluate the relationships between textural features of the primary tumor on FDG PET images and clinical-histopathological parameters which are useful in predicting prognosis in newly diagnosed non-small cell lung cancer (NSCLC) patients. MATERIAL AND METHODS: PET/CT images of ninety (90) patients with NSCLC prior to surgery were analyzed retrospectively. All patients had resectable tumors. From the images we acquired data related to metabolism (SUVmax, metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) and texture features of primary tumors. Histopathological tumor types and subgroups, degree of Ki-67 expression and necrosis rates of the primary tumor, mediastinal lymph node (MLN) status and nodal stages were recorded. RESULTS: Among the 2histologic tumor types (adenocarcinoma and squamous cell carcinoma) significant differences were present regarding metabolic parameters, Ki-67 index with higher values and kurtosis with lower values in the latter group. Textural heterogeneity was found to be higher in poorly differentiated tumors compared to moderately differentiated tumors in patients with adenocarcinoma. While Ki-67 index had significant correlations with metabolic parameters and kurtosis, tumor necrosis rate was only significantly correlated with textural features. By univariate and multivariate analyses of the imaging and histopathological factors examined, only gradient variance was significant predictive factor for the presence of MLN metastasis. CONCLUSIONS: Textural features had significant associations with histologic tumor types, degree of pathological differentiation, tumor proliferation and necrosis rates. Texture analysis has potential to differentiate tumor types and subtypes and to predict MLN metastasis in patients with NSCLC.

Correction to: Demineralized bone matrix and hydroxyapatite/tri-calcium phosphate mixture for bone healing in rats.

The first name of one author is missing in the published article. The correct abbreviation: H.C. Gemalmaz.

Relationship between primary lesion metabolic parameters and clinical stage in lung cancer.

OBJECTIVES: The relation of PET-derived parameters as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV) with clinical stage in lung cancer and correlation of SUVmax of primary tumor and that of metastatic lesion was studied in lung cancer patients. MATERIALS AND METHODS: Patients with lung cancer who were referred for FDG PET/CT were included in the study. RESULTS: PET/CT scans and pathology reports of 168 patients were assessed. A total of 146 (86.9%) of these patients had a diagnosis of non-small cell lung cancer (NSCLC) and 22 (13.1%) had small cell lung cancer (SCLC). Metabolic parameters such as SUVmax, TLG and MTV showed significant differences in all the stages in NSCLC patients (p<0.001). However, after tumors sizes <25 mm were excluded, no significant differences in SUVmax between stages were observed. No significant differences were found between these metabolic parameters and limited or extended disease SCLC. Tumor diameter correlated with primary tumor SUVmax and significant correlations between primary lesion SUVmax and metastatic lesion SUVmax were found. CONCLUSIONS: Although differences were found regarding indices between stages of NSCLC cases, SUVmax differences between stages seem to be caused by underestimation of SUVmax in small lesions. Other glucose metabolism indexes such as MTV and TLG show promising results in terms of prognostic stratification. Future studies are needed for better understanding of their contribution to clinical cases.

Expression and clinical significance of Ki-67, oestrogen and progesterone receptors in acoustic neuroma.

OBJECTIVE: The objective was to assess the presence of Ki-67, and oestrogen and progesterone hormone receptors as well as their clinical correlates in acoustic neuroma. METHODS: Medical records of 59 patients who were operated on for acoustic neuroma between 1995 and 2003 were evaluated retrospectively. Formaldehyde-fixed paraffin-embedded archival acoustic neuroma specimens of the patients were used for immunohistochemical assessments of oestrogen and progesterone hormone receptors, and Ki-67 proliferative marker. RESULTS: Tumour sizes were small (40 mm) in 21, 35 and 3 patients, respectively. On immunohistochemistry, all samples were (+) for progesterone receptor and (-) for oestrogen receptor staining. Ki-67 staining was encountered in 34 of 59 (57.6 per cent) patients, and Ki-67 values ranged from 0 per cent to 10.9 per cent (mean 1.36 per cent). There was no correlation between Ki-67, gender, tumour size and symptoms of the patients (p > 0.05). CONCLUSION: Oestrogen is not an important hormone in acoustic neuroma due to the absence of oestrogen receptor expression in the tissue samples. Since the progesterone receptor is expressed in all acoustic neuroma samples, further studies are necessary to find out about the inhibitory effect of antiprogesterone treatment on acoustic neuroma growth, which may be important particularly in elderly people or high-risk patients. Although Ki-67 is expressed in the majority of acoustic neuromas, it is not an important marker in clinical practice due to a lack of any correlation with the clinical parameters.

Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma.

The aim of this study was to compare vascular endothelial growth factor (VEGF), CD 34, and endoglin expressions as markers of angiogenesis in proliferative endometrium (PE), endometrial hyperplasia (EH), and endometrial carcinoma (EC) and to find the possible impact of angiogenesis on malign transformation. Formalin-fixed, paraffin-embedded tissues from 12 patients with PE, 23 patients with simple EH and complex EH with atypia, and 31 patients with EC were included. A semiquantitative scoring system was used to assess the intensity and degree of staining of VEGF. Microvessel density (MVD) was assessed with endoglin and anti-CD 34 in most vascular areas. VEGF expression was significantly higher in EC and EH than PE, but there was no difference between EC and EH. According to CD 34 staining, there were no differences in MVD between groups. However, mean MVD counts assessed by endoglin were significantly higher in EC than PE and EH. Although VEGF expression in EC was significantly higher, it did not correlate with other measures of angiogenesis. MVD using endoglin seemed to reflect neoplastic angiogenesis better than CD 34.

Demineralized bone matrix and hydroxyapatite/tri-calcium phosphate mixture for bone healing in rats.

PURPOSE: Hydroxyapatite/tri-calcium phosphate (HA/TCP) mixture is an osteoconductive material used as a bone graft substitute, and demineralised bone matrix (DBM) is an osteoinductive material. A combination of DBM and HA/TCP mixture would probably create a composite with both osteoconductive and osteoinductive properties. The purpose of this study was to determine the effect of the combination of DBM and HA/TCP mixture on healing of rat radius segmental defects. METHODS: Twenty-four adult male Wistar rats were used. Bilateral radial defects were created in each animal. Radial defects were implanted with DBM, HA/TCP mixture and a combination of both substances. Control defects were left unfilled. Ten weeks after implantation, the animals were sacrificed, and the radii were evaluated by radiograhic and histopathological studies. RESULTS: The use of DBM alone demonstrated improved healing on radiographic and histological studies compared to other groups and the control group. There were no differences between the other two groups and the control group. CONCLUSION: The DBM group showed the best healing response. Combined use of DBM and HA/TCP mixture did not improve bone healing, and the osteoinductive properties of DBM were inhibited by HA/TCP mixture.

Presentation of interleukin-12/-23 receptor beta1 deficiency with various clinical symptoms of Salmonella infections.

Clinical disease caused by weakly pathogenic mycobacterial species, Mycobacterium bovis Bacille Calmette-Guérin (BCG) and non-tuberculous environmental mycobacteria (EM), which is known as Mendelian susceptibility to mycobacterial disease (MSMD), is a rare entity defined recently. Infections with the more virulent Mycobacterium species, M. tuberculosis, may have largely gone unnoticed in these patients due to early death. Mutations in five proteins (IFNgammaR1, IFNgammaR2, IL-12/IL-23Rbeta1, IL-12/IL-23p40 and STAT1) have been found in MSMD. These patients are prone to surprisingly few other infectious diseases mainly to salmonellosis. Here we present three IL-12/IL-23Rbeta1 deficient patients from three different families and with different genetic mutations, who presented exclusively with Salmonella infections. Bacteremia and lymph node involvement were common clinical expressions. Leukocytoclastic vasculitis developed in one of these patients. Two patients were not inoculated with BCG, the third patient did not develop BCG infection although BCG vaccine had been given twice at ages of 1 and 7 years. All three patients responded well to antibiotic treatment. In conclusion, patients with chronic, recurrent or complicated Salmonella infections should be screened for MSMD, particularly for IL-12/IL-23p40/IL-12R/-23Rbeta1 deficiency. Conversely, in patients with genetic IL-12/-23Rbeta1 deficiency a full evaluation for Salmonella infection is required. IL-12/IL-23p40/IL-12R/IL-23Rbeta1 deficiency seem to be underdiagnosed in patients with salmonellosis, and since such patients need prolonged therapy, diagnosis is important.

A patient with occult breast cancer presenting with an axillary lymph node metastasis and a synchronous contralateral breast cancer.

Detection of a breast mass accompanied by a contralateral axillary lymphadenopathy presents a dilemma because of the possible presence of an occult breast cancer on the same side as the axillary lymphadenopathy. A patient presented with an axillary lymphadenopathy from an occult breast cancer and a synchronous contralateral breast cancer, for which the differential diagnosis was established through a significant difference in estrogen and progesterone receptor levels. The patient was treated with neoadjuvant chemotherapy followed by bilateral modified radical mastectomy, adjuvant chemotherapy, and adjuvant radiation therapy. She is alive and free of disease 1.5 years after the diagnosis.

Epididymal metastasis from gastric signet ring cell adenocarcinoma.

We report a 55 year old man complaining of painless left testicular swelling that developed over 2 months. The imaging studies revealed an epididymal mass separate from the testicle. The patient underwent left radical orchiectomy. The histopathological examination of the orchiectomy specimen revealed poorly differentiated signet cell metastatic adenocarcinoma.

Acute necrotizing tubulointerstitial nephritis due to systemic adenoviral infection.

To date, all the reported cases of acute necrotizing tubulointerstitial nephritis (TIN) secondary to systemic adenovirus infection have occurred in individuals with primary or secondary immunodeficiency, and have resulted in renal failure and death. We present the case of a 12-year-old, immunologically competent girl who developed acute necrotizing TIN with acute renal failure (ARF), hepatitis and meningoencephalitis secondary to a systemic adenoviral infection who completely recovered with supportive care.

Positive effect of low molecular weight dextrans on the early graft function.

This study evaluates the effect of the low molecular weight dextrans as a perfusion solution on early graft function of twenty living donor kidneys. Ten kidneys were perfused with +4 degrees C Ringer lactate after nephrectomy while other ten with +4 degrees C Ringer lactate + 10% Dextran. Immediate and delayed kidney function, blood creatinine, postoperative hemodialysis requirement, Doppler US and renal scintigraphy, third month graft survival and number of removed grafts were examined postoperatively as well as kidney biopsies. No statistical difference was found between the groups regarding the post-transplant ATN period. But the microscopic examinations demonstrated less damage-more function in Ringer lactate+Dextran group compared to Ringer lactate alone.

A case of multiple synchronous localized fibrous tumor of the pleura.

We report a patient with two synchronous distinct masses in the same hemithorax both of which got the diagnosis of benign localized fibrous tumor of the pleura. The plain chest X-ray was rather obscured due to a large left-sided pleural effusion, but her subsequent computerized chest tomography revealed a heterogeneous hypodense soft tissue mass, which was pleural in origin, sitting on the diaphragm bathed in fluid. At thoracotomy, we detected two distinct masses in the left hemithorax, both arising from the visceral pleura via their vascular pedicles.

Clinical importance of correlations between p53 immunoreactivity and clinicopathological parameters in lung carcinoma.

Many studies have revealed the frequency of p53 abnormalities in lung cancer. However, clinico-pathological studies of p53 abnormalities have yielded conflicting results. We examined the p53 immunoreactivity and studied the correlations of p53 status and clinicopathological parameters in 76 primary lung cancers. By using DO-7 antibody, different degrees of p53 immunoreactivity was detected in 8 of 30 small cell lung cancer (SCLC, 26.6%) and 22 of 46 non-small cell lung cancer (NSCLC, 47.8%), 6 of 19 adenocarcinoma, 16 of 27 epidermoid carcinoma cases. In the whole group, no correlation was detected between the p53 status and the histological types of tumor, local tumor invasion, nodal status, and distant metastasis and patient characteristics, such as age, gender or smoking habit. P53 status was also found to have no effect on survival. However, in the NSCLC group, there was a significantly higher p53 immunoreactivity in well- and moderately-differentiated tumors (p<0.05). Patients with p53 immunoreactivity had a poor therapeutic response in the whole group. We concluded that, although p53 immunreactivity may be found in NSCLC, this does not correlate with clinicopathological parameters except therapeutic response. In SCLC p53 immunreactivity can be negligible.

P53 and proliferating cell nuclear antigen (PCNA) expression in non-tumoral liver diseases.

The tumor suppressor gene p53 is known to be involved in the negative regulation of cell growth. Proliferating cell nuclear antigen (PCNA), which is a nuclear protein and a component of the DNA replication process, is also involved in growth regulation. Both have been studied as progression markers in various tumors including hepatocellular carcinoma. In the present study, the aberrant p53 protein and PCNA expressions in non-tumoral liver diseases were investigated. Using monoclonal antibodies anti-p53 (D07-DAKO) and anti-PCNA (PC10-DAKO), 149 samples were stained, including 10 normal and 10 tumoral control liver tissues. p53 Overexpression was detected in 52 specimens (35%) whereas PCNA positivity was found in 96 (64%). There were 21 different pathological entities but most of the positive samples could be grouped into four types of diseases; namely, non-specific reactive hepatitis, steatohepatitis, chronic hepatitis and cirrhosis. Statistical analyses performed on these groups revealed that p53 positivity was found to be significantly higher in steatohepatitis (P < 0.05), while PCNA positivity did not show any statistical significance. The number of samples showing both p53 and PCNA positivity was 42 but their coexistence was not found to be significant. Certain cytological alterations like nuclear pleomorphism, steatosis and cholestasis, in addition to necroinflammatory activity, were evaluated for their possible impact on p53 and/or PCNA positivity. Necroinflammatory activity in steatohepatitis and steatosis in chronic hepatitis was found to be significant for p53 positivity (P < 0.05). In contrast, nuclear pleomorphism in non-specific reactive hepatitis was found to be significant for PCNA positivity (P < 0.05).

Henoch Schönlein purpura and amebiasis.

The pathogenesis of Henoch Schönlein purpura (HSP) is unknown but is believed to result from an immune complex reaction to various antigenic stimuli, such as infectious agents. However, its association with Entamoeba histolytica has not been reported before. We present an 11-year-old boy with HSP, confirmed by the demonstration of leukocytoclastic vasculitis from skin and diffuse endocapillary proliferative glomerulonephritis, together with immunoglobulin A and complement component C3 deposition from renal biopsies. Cysts and trophozoites of Entamoeba histolytica were detected from the stool of the patient at the same time and disappeared after the treatment with metranidasole. The temporal association of these two disorders is either coincidental or due to a causal relationship between them.

Effect of nordihydroguaretic acid and fluconazole on the LTC4/PGE2 ratio in the kidney of mice damaged by Candida albicans.

The kidney is a major target organ in generalized candidiasis. When mice were infected with C.albicans, prostaglandin E2 (PGE2)-like activity was found to be significantly decreased while leukotriene C4 (LTC4)-like activity increased in the kidneys within 10 days. The aim of this study is to investigate the effect of nordihydroguaretic (NDGA) and fluconazole on the LTC4/PGE2 ratio in the mice kidneys infected by proteinase (+) C. albicans. The LTC4/PGE2 ratio was found to be significantly decreased both in NDGA and fluconazole-pretreated groups. These results indicate that pretreatment with the lipoxygenase inhibitor NDGA and the antifungal drug fluconazole, protect the kidney against C. albicans infection. These results also indicate a possible role of arachidonic acid metabolites (increase LTC4 and decrease PGE2) in kidney damage due to C. albicans infection.