Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology.

PURPOSE: The nonthermal irreversible electroporation (NTIRE) is a novel potential ablation modality for renal masses. The aim of this study was the first evaluation of NTIRE's effects on the renal urine-collecting system using intravenous urography (IVU) and urinary cytology in addition to histology and magnetic resonance imaging (MRI). METHODS: Eight percutaneous NTIRE ablations of the renal parenchyma, including the calyxes or pelvis, were performed in three male swine. MRI, IVU, histology, and urinary cytology follow-ups were performed within the first 28 days after treatment. RESULTS: MRI and histological analysis demonstrated a localized necrosis 7 days and a localized scarification of the renal parenchyma with complete destruction 28 days after NTIRE. The urine-collecting system was preserved and showed urothelial regeneration. IVU and MRI showed an unaltered normal morphology of the renal calyxes, pelvis, and ureter. A new urinary cytology phenomenon featured a temporary degeneration by individual vacuolization of detached transitional epithelium cells within the first 3 days after NTIRE. CONCLUSIONS: This first urographical, urine-cytological, and MRI evaluation after porcine kidney NTIRE shows multifocal parenchyma destruction while protecting the involved urine-collecting system with regenerated urothelial tissue. NTIRE could be used as a targeted ablation method of centrally located renal masses.

Synthesis and localization of trefoil factor family (TFF) peptides in the human urinary tract and TFF2 excretion into the urine.

Trefoil factor family (TFF) peptides promote regeneration and repair processes of mucous epithelia. They also probably play a key role in the remarkable regenerative capacity of the urinary tract epithelia. We have localized TFF1, TFF2, and TFF3 expression systematically in surgical specimens from the urinary tract by reverse transcription with the polymerase chain reaction, Western blot analysis, and immunohistochemistry. Urine samples from patients suffering from nephrolithiasis have been investigated and compared with those of healthy controls. TFF synthesis is detectable along the entire urinary tract epithelia. TFF3 synthesis is the most pronounced followed by TFF1, whereas TFF2 synthesis is occasionally detectable but only in trace amounts. In contrast, TFF2 is the predominant TFF peptide excreted into the urine, and significantly increased urinary TFF2 levels (together with occasionally raised TFF3 levels) have been observed in patients suffering from nephrolithiasis. Thus, we consider that TFF3 plays a major part in regeneration and restitution processes in urinary tract epithelia. TFF2 and probably also TFF3 are candidate biomarkers for nephrolithiasis and possibly other inflammatory conditions of the urinary tract.

Meconium-induced periorchitis.

A testicular tumour-like lesion or a solid extratesticular mass are serious postnatal problems with a broad spectrum of inflammatory or tumorous causes and possible differential diagnoses. In this case report, an extraordinary case of a newborn boy with a rare cause of a periorchitis is described.A premature boy infant (25-year-old mother with obesity) was diagnosed as having a disturbance of prosperity. A plain film of the abdomen showed a dilated intestine (no pathological findings in abdominal ultrasound, in particular, no ascites). After 3 postnatal months of clinical observation at the hospital including temporary parenteral nutrition, hydrocele at both sides was diagnosed. Therefore, the boy underwent surgical exploration. Intraoperatively, the processus vaginalis peritonei was surprisingly filled with meconium; because of that, the situs was extensively rinsed. In addition, the boy underwent an operation for the right and left hydrocele. The testes were preserved (on follow-up investigation there were no further problems).Pathohistological investigation confirmed meconium periorchitis, which is a rare postnatal disease and which can only develop in cases of former meconium peritonitis and if the processus vaginalis peritonei is open. The precise details of cause and pathophysiology in this case may significantly help in avoiding unnecessary orchiectomy.

Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer.

A critical region of loss of heterozygosity on human chromosome 13q14 harbors the tumor suppressor gene DICE1 (DDX26). To elucidate the reduced DICE1 expression in tumor cells, the putative promoter sequence upstream of the DICE1 gene was analysed. This sequence shows a high GC content and is rich in CpG sites and binding sites of transcriptional factors. Promoter activity was identified within three overlapping fragments of the 800 bp sequence upstream of the DICE1 gene. A 13 bp deletion polymorphism detected in the DICE1 promoter region showed a decreased activity compared with the undeleted variant. However, this 13 bp deletion was seen in male control samples and patients with prostate cancer or benign prostatic hyperplasia at similar rates. A reduced DICE1 expression was observed in prostate cancer cell lines DU145 and LNCaP. This downregulation is associated with hypermethylation of the DICE1 promoter. Treatment of both prostate cancer cell lines with 5-azacytidine leads to upregulation of DICE1 expression. Hypermethylation of CpG sites of the DICE1 promoter was observed in four of eight analysed prostate cancers. This study suggests that transcriptional repression of DICE1 is caused by hypermethylation of the DICE1 promoter region in prostate cancer cells.

Metastatic adrenal neuroblastoma in an adult.

BACKGROUND: Neuroblastoma (NB) is a common malignancy in children, but rarely occurs in adults. Accepted unfavourable prognostic factors include age > 1 year, low histologic grade and advanced stage, MYCN amplification, chromosomal aberrations, elevations of neuron specific enolase and lactate dehydrogenase, and increased catecholamine metabolites in urine or serum. In adults, abdomen/retroperitoneum are the primary sites and in children the adrenal gland. CASE REPORT: A 51- year-old man was admitted to our hospital with hypertension and a large right retroperitoneal mass. Clinically, phaeochromocytoma was suspected. Tumour resection revealed adrenal NB grade III. Chemotherapy according to the paediatric German Neuroblastoma Trial (NB97) was started. Follow-up computed tomography showed regression of the enlarged mediastinal and retroperitoneal lymph nodes. Because of local and systemic progression palliative radiochemotherapy was started. The patient died 9 months after diagnosis. CONCLUSION: To the best of our knowledge this is the oldest NB patient registered so far in Germany. Currently there are no standard treatment guidelines for patients with NB in adulthood. Collection and evaluation of data in adult patients with this tumour are warranted in order to optimise treatment strategies.

Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia.

BACKGROUND: Evidence is accumulating that several proteases are involved in prostate cancer progression. A locus which is often amplified in prostate cancer is the chromosomal region 20q13. Interestingly, one of the genes encoding the cysteine protease cathepsin X maps to this region. The aim of this study was to assess the expression pattern of cathepsin X in malignant and non-malignant prostatic tissue samples. METHODS: Matched malignant and non-malignant tissue specimens were obtained from 56 men after radical prostatectomy. Cathepsin X was quantified at both protein and mRNA levels using several detection methods: Western blotting, immunohistochemistry, quantitative RT-PCR, and in situ hybridization. Furthermore, genomic DNA was analyzed by PCR for possible gene amplification. RESULTS: Immunohistochemical analysis of formalin-fixed, paraffin-embedded sections of radical prostatectomy specimens was performed utilizing a polyclonal antibody against human procathepsin X and revealed staining of acinar basal cells in normal prostate glands. Prostatic intraepithelial neoplasias (PINs) and prostate carcinomas stained highly positive for cathepsin X, showing a significant difference to the staining of normal prostate glands. In contrast, relatively weak and heterogeneous staining was observed for cathepsins F, B, and L. Up-regulation of cathepsin X at the protein level was confirmed by Western blotting. No statistically significant difference was observed at the mRNA level. PCR of genomic DNA revealed that cathepsin X up-regulation most likely occurs in the absence of genomic amplification. CONCLUSIONS: The high expression levels of cathepsin X both in PIN and invasive adenocarcinomas of the prostate suggest that cathepsin X may play a role in the early tumorigenesis of prostate cancer. Further studies are needed to define the utility of this cysteine protease as a diagnostic marker for the early detection of prostate cancer.

Retention of the arginine allele in codon 72 of the p53 gene correlates with poor apoptosis in head and neck cancer.

The allele constitution at codon 72 of the p53 gene (CGC-arginine or CCC-proline) plays a major role in inducing apoptosis in p53 mutant cells. To verify this, we determined GC-status, p53-mutations, and p53-loss of heterozygosity (LOH) in a group of 54 squamous cell carcinomas of the head and neck (SCCHN). A novel approach, using a one-step real-time PCR analysis with fluorescent hybridization probes, was applied to detect the GC status in tumors and corresponding blood samples. p53 mutations in exons 4 to 8 were detected by PCR-SSCP-sequencing analysis. Apoptosis was determined immunohistochemically using antibodies against Fas, FasL, p53, Bcl2, and terminal deoxy-transferase-mediated dUTP nick end labeling (TUNEL) staining. The overall frequency of p53-LOH in SCCHN was 45.2%. In cases of LOH, there was a preferential loss of the proline allele, which was associated with an up-regulation of Bcl2 and lack of co-expression of Fas/FasL and, thus, impaired apoptosis (P < 0.001). Apoptosis was not observed in tumors carrying the arginine allele. p53 mutations were detected in 29.6% of SCCHN and preferentially occurred at the arginine allele (P = 0.01). p53 alterations were more frequently observed in tumors of the oral cavity, oropharynx and hypopharynx, whereas they were rare in larynx carcinomas (P = 0.07). The p53-LOH status was not found to be significantly correlated with sex, age, TNM-status, or tumor grading. We conclude that apoptosis is correlated with the allelic status of codon 72 in SCCHN. Homozygous proline 72 appears to be an important regulator of apoptosis via the Fas/FasL pathway in SCCHN.

Rhinoscleroma associated with Rosai-Dorfman reaction of regional lymph nodes.

Rhinoscleroma is an uncommon chronic, destructive infection of the respiratory mucosa caused by Klebsiella rhinoscleromatis. This coccobacillus can be found in the typical histiocytes, the Mikulicz cells. Extranasal and nodal involvement in this disease is rare, but documented. Rosai-Dorfman disease or sinus histiocytosis with massive lymphadenopathy is also a rare, non-hereditary disorder. Bilateral cervical lymphadenopathy with emperipolesis, as the main histological characteristic, is the most common presentation. It can also occur extranodally. We report a case of rhinoscleroma occurring in a 62-year-old woman since 1984, who developed parotid gland and lymph node involvement. The changes in the nasal mucosa and the parotid gland showed chronic inflammation with Mikulicz cells. In the lymph nodes, features characteristic of Rosai-Dorfman disease were seen. Taking into consideration the literature dealing with both of these diseases, we discuss that Rosai-Dorfman disease could be a special type of lymph node reaction and is not necessarily an entity of its own. Therefore, it should be known as Rosai-Dorfman lymph node reaction. Furthermore, there seems to be an interconnection between Rosai-Dorfman disease and rhinoscleroma.

Prognostic value of MMP-2, -9 and TIMP-1,-2 immunoreactive protein at the invasive front in advanced head and neck squamous cell carcinomas.

In head and neck cancer as well as in other carcinomas, tumor expansion and spread to distant sites require the secretion of destructive enzymes that degrade the extracellular matrix. A variety of proteases contribute to matrix destruction. Characteristics of the invasive tumor front may reflect tumor prognosis better than do other parts of the tumor. Therefore, it was the aim of the present study to (i) compare central and peripheral tumor zones for differences in the expression of matrix-metalloproteinases (MMP) -2 and -9 and their naturally occurring inhibitors (tissue inhibitor of matrix-metalloproteinases (TIMP) -1 and -2), (ii) examine the morphological potential of malignancy, and (iii) correlate these findings with clinicopathological parameters. The study population consisted of 106 surgical specimens of advanced head and neck squamous cell carcinomas. The invasive front was graded for malignancy, and immunohistochemical staining with MMP-2, MMP-9, TIMP-1 and TIMP-2 antibodies was performed. Both MMP-2 and MMP-9 were found to be significantly overexpressed at the tumor front. The MMP-2-positive invasive front exhibited diminished overall survival times. In multivariate analysis, MMP-2 expression retained its correlation with overall survival in addition to nodal status and total malignancy score. Expression of TIMP-2 correlated with local tumor invasion. We conclude that the expression of MMP-2 at the invasive front is a marker of poor survival and appears to be associated with early recurrence in initially lymph node-negative patients.

[Manifestation of Cushing syndrome and osteoporotic fractures in pregnancy in a patient with Carney complex]. / Manifestation eines Cushing-Syndroms und osteoporotischer Frakturen in der Schwangerschaft einer Patientin mit Carney-Komplex.

HISTORY AND CLINICAL FINDINGS: In a 31-year-old patient a conventional X-ray was performed due to persistent pain at the lumbar spine level after a cesarean section. It revealed compression fractures of L2 and L3. Besides very clear clinical signs of hypercortisolism, multiple hyperpigmentations and naevi in the patient's face including the lips and the conjunctiva of the right eye were visible, suggesting a Carney complex. INVESTIGATIONS: Insuppressible cortisol levels confirmed an adrenal origin of hypercortisolism. A selective catheterization of adrenal veins supported the presence of bilateral adrenal cortisol production. The computed tomography showed nodular lesions in the right and a hyperplasia of the left adrenal gland. TREATMENT AND COURSE: A bilateral adrenalectomy was performed and a primary pigmented nodular adrenal hyperplasia was confirmed histologically. Clinical signs of hypercortisolism rapidly resolved after adrenalectomy. CONCLUSIONS: The diagnosis of Cushing's syndrome as a part of Carney complex was diagnosed at the end of a pregnancy although signs of hypercortisolism were present a long time before. The rare diagnosis of Carney complex should be considered in patients exhibiting symptoms of hypercortisolim and the typical clinical signs (hyperpigmentations).