Detection of prostate cancer by radio-frequency near-field spectroscopy in radical prostatectomy ex vivo specimens.

BACKGROUND: The aim of radical prostatectomy (RP) is the complete removal of the prostate gland with negative surgical margins. The presence of cancer at the surgical margin is associated with higher probability of disease progression. Current methods of intraoperative margin assessment are inaccurate or time-consuming.The study goal was to evaluate the ability of a novel device (Dune Medical Devices) to differentiate between cancer and BPH. METHODS: A total of 49 patients undergoing RP in four medical centers between November 2007 and May 2008 were enrolled in this study.The device was applied to numerous intra- and extra-capsular sites of freshly excised RP specimens. Measurement sites were accurately marked and analyzed histologically. The ability of the device to differentiate between malignant and nonmalignant sites was assessed. RESULTS: A total of 15,156 measurements from 45 patients were analyzed. Differentiation of the intra-capsular malignant sites from extra-capsular nonmalignant sites (bladder neck and apex regions) depends on the cancer feature size. Differentiation was achieved with sensitivity and specificity of 93.6 (95% confidence interval (CI): 88-98) and 94.1 (95% CI: 93-95), respectively, at feature sizes at or >0.8 mm in diameter. The device was able to discriminate between all intra-capsular malignant (with feature sizes down to a few cells) and nonmalignant measurement sites, with sensitivity and specificity of 80.8 (95% CI: 73-87) and 68.4 (95% CI: 67-69), respectively. CONCLUSIONS: First results from a radio-frequency near-field spectroscopy sensor look promising for differentiation between cancer and benign prostate tissue. The sensor's dimensions (radius of ~ 1 mm) and design enable use in open, laparoscopic and robotic RP to evaluate the surgical margins intraoperatively.

Nitric oxide synthase immunoreactivity in human bladder carcinoma.

AIMS: To study the expression of the endothelial and inducible isoforms of nitric oxide synthase (eNOS and iNOS, respectively) in human bladder carcinoma and schistosomal bladder disease, and to compare it with normal adult and fetal urothelium. Nitric oxide is thought to play a complex role in human carcinogenesis, but has only recently been investigated in bladder cancer. METHODS: Immunohistochemistry was performed on paraffin wax embedded sections of 33 human bladder carcinomas and five bladder carcinoma cell lines; in addition, seven schistosomal bladder cases and normal and fetal urothelium were investigated. In the cell lines enzymatic activity was examined by the NADPH diaphorase reaction. RESULTS: Immunoreactivity for eNOS was present in most cells of all 31 cases examined. Immunoreactivity for iNOS was less abundant and was seen in 23 of 25 cases. Similar findings were noted in schistosomal bladder cancer. In the normal bladder mucosa, eNOS immunoreactivity was found only in the superficial cell layer and iNOS was not expressed, whereas in the fetal urothelium immunoreactivity for both isoforms was seen in all cell layers. Enzymatic activity and immunoreactivity for eNOS and iNOS were evident in the five bladder carcinoma cell lines. CONCLUSIONS: It is possible that NOS plays a role in the differentiation of the transitional epithelium in fetal life, has a biological function in the adult bladder mucosa, and is involved in bladder carcinogenesis. eNOS and iNOS immunoreactivity do not differ in schistosomal and non-schistosomal bladder carcinoma, but resemble the pattern of expression typical of fetal urothelium.

Detection of human herpesvirus-8 DNA in kidney allografts prior to the development of Kaposi's sarcoma.

Human herpesvirus-8 (HHV-8) DNA was identified in kidney allografts in 2 of 3 transplant recipients prior to the development of Kaposi's sarcoma, and increase in viral antibody titer was found in the third. Combined genotypic and serologic analyses could be used to identify patients at risk and suggest that the kidney may be a site of HHV-8 latency.

The imprinted H19 gene is a marker of early recurrence in human bladder carcinoma.

AIMS: To investigate the expression of the imprinted oncofetal H19 gene in human bladder carcinoma and to examine the possibility of using it as a tumour marker, similar to other oncofetal gene products. METHODS: In situ hybridisation for H19 RNA was performed on 61 first biopsies of bladder carcinoma from Hadassah Medical Centre in Jerusalem. The intensity of the reaction and the number of tumour cells expressing H19 in each biopsy were evaluated in 56 patients, excluding biopsies with carcinoma in situ. The medical files were searched for demographic data and disease free survival. RESULTS: More than 5% of cells expressed H19 in 47 of the 56 (84%) biopsies. There was a decrease in the number of cells expressing H19 with increasing tumour grade (loss of differentiation) (p = 0.03). Disease free survival from the first biopsy to first recurrence was significantly shorter in patients with tumours having a larger fraction of H19 expressing cells, controlling for tumour grade. This was also supported by the selective analysis of tumour recurrence in patients with grade I tumours. CONCLUSIONS: It might be possible to use H19 as a prognostic tumour marker for the early recurrence of bladder cancer. In addition, for the gene therapy of bladder carcinoma that is based on the transcriptional regulatory sequences of H19, the expression of H19 in an individual biopsy could be considered a predictive tumour marker for selecting those patients who would benefit from this form of treatment.

Similarity measurement method for the classification of architecturally differentiated images.

A similarity measurement method for the classification of architecturally differentiated image sections is described. The strength of the method is demonstrated by performing the complex task of assigning severity grading (Gleason grading) to histological slides of prostate cancer. As shown, all that is required to employ the method is a small set of preclassified images. The images can be real world images acquired by means of a camera, computer tomography, etc., or schematic drawings representing samples of different classes. The schematic option allows a quick test of the method for a particular classification problem.

Primary presacral adenocarcinoma. Report of a case.

A rare of a patient who presented with a presacral tumor is described. The tumor, after complete resection, was shown to be a primary adenocarcinoma. After potential sources such as gastrointestinal, pancreas, or prostate were eliminated, the diagnosis of primary presacral adenocarcinoma was made. Possible origins of this unusual tumor are discussed.

The product of the imprinted H19 gene is an oncofetal RNA.

AIMS/BACKGROUND: The H19 gene is an imprinted, maternally expressed gene in humans. It is tightly linked and coregulated with the imprinted, paternally expressed gene of insulin-like growth factor 2. The H19 gene product is not translated into protein and functions as an RNA molecule. Although its role has been investigated for more than a decade, its biological function is still not understood fully. H19 is abundantly expressed in many tissues from early stages of embryogenesis through fetal life, and is down regulated postnatally. It is also expressed in certain childhood and adult tumours. This study was designed to screen the expression of H19 in human cancer and its relation to the expression of H19 in the fetus. METHODS: Using in situ hybridisation with a [35S] labelled probe, H19 mRNA was detected in paraffin wax sections of fetal tissues from the first and second trimesters of pregnancy and of a large array of human adult and childhood tumours arising from these tissues. RESULTS: The H19 gene is expressed in tumours arising from tissues which express this gene in fetal life. Its expression in the fetus and in cancer is closely linked with tissue differentiation. CONCLUSIONS: Based on these and previous data, H19 is neither a tumour suppressor gene nor an oncogene. Its product is an oncofetal RNA. The potential use of this RNA as a tumour marker should be evaluated.

Granulocytic sarcoma of the chest wall at site of Hickman catheter tract.

Insertion of a Hickman central venous catheter before administration of induction chemotherapy is a common practice in treatment of patients with acute myeloblastic leukemia (AML). Granulocytic sarcoma associated with AML may be the initial clinical manifestation of newly diagnosed or relapsed AML, heralding systemic involvement by weeks to months. A case of granulocytic sarcoma of the chest wall occurring as subcutaneous nodules along a scar of a previous Hickman catheter tract in a 45 year old female patient with AML is described. The patient who was in first complete remission, developed granulocytic sarcoma simultaneously with complaints associated with leukemic CNS infiltration. This is the second case described of granulocytic sarcoma of the chest wall at the site of a Hickman catheter tract. The simultaneous CNS and chest wall manifestations raise the interesting question whether both sites behaved as sanctuaries for resistant leukemic cells, in this case.

Hepatitis C virus viremia in SCID-->BNX mouse chimera.

Chimpanzees are currently the only nonhuman animal model for reproducible propagation of hepatitis C virus (HCV). A chimeric mouse model was used for the induction of hepatitis C viremia, using BNX (beige/nude/X-linked immunodeficient) mice preconditioned by total body irradiation and reconstituted with SCID mouse bone marrow cells. HCV-infected liver fragments from patients with HCV RNA-positive sera were transplanted under the kidney capsule of the chimeric mice. HCV-specific RNA sequences were detected by reverse transcriptase nested polymerase chain reaction (RT-PCR) in serum of approximately 50% of grafted animals. In addition, normal liver specimens were incubated with HCV serum and transplanted into chimeric mice, leading to viremia in approximately 25% of animals. Sequential histologic evaluation of the liver implants, from day 2 to week 14 after transplantation, revealed loss of lobular architecture within the implants. However, viremia persisted for 10-50 days after transplantation. These results offer a new HCV model.

Malignant neuroepithelioma of the colon.

A rare case of malignant peripheral neuroepithelioma originating from the right colon is presented. The patient underwent right hemicolectomy followed by combination chemotherapy and there has been no evidence of tumour recurrence or metastases during three years of follow up. Emphasis is given to the extremely unusual location of this tumour and the favorable clinical outcome.

The imprinted H19 gene as a tumor marker in bladder carcinoma.

OBJECTIVES: Genomic imprinting is a newly discovered mechanism in genetics that is involved in tumorigenesis. H19 is an imprinted gene in the human, expressed from the maternal allele. It is extensively transcribed in fetal life but is not translated and functions as an RNA molecule. It has been suggested as a candidate tumor suppressor gene. We studied the expression of H19 in human cancer arising from tissues expressing H19 in fetal life, one of which is bladder mucosa. METHODS: In situ hybridization for H19 mRNA on paraffin sections of bladder carcinoma in different histologic grades. RESULTS: Low-grade (grade 1 of 3), noninvasive (Ta) papillary transitional cell bladder carcinoma did not express H19, but prominent expression was disclosed in higher grades, invasive transitional cell carcinomas (T1-T3/4). Expression was also evident in in situ bladder carcinoma (Tis), which tends to progress rapidly to invasive cancer. CONCLUSIONS: We suggest that H19 can be used as a tumor marker in human bladder carcinoma, where its expression indicates a more malignant potential.

Hepatitis B virus infection associated with hematopoietic tumors.

Hepatitis B virus (HBV) infection and replication have been linked to the development of hepatocellular carcinoma. Bone marrow-derived cells, as well as mesenchymal and epithelial cells, were recently shown to support HBV replication. We hypothesize that the mechanism that links HBV infection and liver tumors might also promote tumor development in tissues permissive for HBV replication. Between 1980 and 1993 we retrospectively identified 22 patients who were hepatitis B surface antigen (HBsAg) carriers and had extra-hepatic malignancies. These patients had 25 tumors, of which 22 were bone marrow derived. HBsAg was detected by immunohistochemistry in bone marrow cells of leukemia patient and of 3 of 10 lymphoma patients. In addition, in 4 of 10 patients with lymphoma, including 2 patients in which HBsAg stained bone marrow cells, HBsAg was also detected in the endothelial cells of blood vessels of the tumor tissue. These results suggest that the identification of an HBV gene product in endothelial cells might point to a role of HBV infection in the development of certain hematopoietic tumors, possibly through activation of cytokines or growth factors, which may eventually lead to bone marrow cell proliferation.

Colchicine induced remission in amyloid nephrotic syndrome.

An unusual case of reversible reactive amyloidosis (AA) is described. A patient in the course of lobar pneumonia developed acute transient nephrotic syndrome and renal failure. Renal and liver biopsy showed amyloidosis and positive immunohistochemistry stains for amyloid A protein. The nephrotic syndrome resolved completely following 6 months of colchicine treatment and the urine is protein free after 6 years of follow-up.

Influence of capsular penetration on progression following radical prostatectomy: a study of 196 cases with long-term followup.

We studied 196 radical prostatectomy cases performed for clinical stage B prostate cancer with capsular penetration; in all cases seminal vesicles and lymph nodes were free of tumor. The mean followup in patients who showed no evidence of progression was 5 years. Focal capsular penetration was seen in 93 cases. There was no difference in progression in this group, irrespective of whether margins were negative or positive. High grade tumors (Gleason score 7 or more) had a significantly higher risk of progression compared to lower grade tumors (p = 0.0002). Established capsular penetration was seen in 103 tumors. Cancers with established capsular penetration had a higher risk of progression than those with focal capsular penetration. Established capsular penetration tumors were stratified into 3 groups with increasing risks of progression: 1) margins were negative and grade was low, 2) margins were positive or grade was high yet both adverse features were not present or 3) margins were positive and grade was high. The differences in progression among these 3 groups were statistically significant. Because of the negligible influence of positive margins in patients with focal capsular penetration the status of capsular margins should not influence the decision on whether to administer immediate postoperative adjuvant therapy. To evaluate the efficacy of adjuvant therapy following radical prostatectomy, tumors with capsular penetration should be stratified into groups having similar risks of progression according to the extent of capsular penetration, surgical margins of resection and grade.

Correlation of pathologic findings with progression after radical retropubic prostatectomy.

BACKGROUND: This study was performed to evaluate the effect of positive margins, Gleason grade, and capsular penetration on progression after radical prostatectomy. METHODS: The authors followed 507 men with totally embedded retropubic prostatectomy specimens performed for clinical Stages A and B prostate cancer for a mean of 3.9 years. RESULTS: Fifty-nine percent of the specimens had negative margins, 37% had focally positive margins, and 4% had extensive positive margins. Although some positive margins were the result of extensive and/or high-grade tumor, in many cases, the tumors only focally reached the capsular margin such that positive margins resulted from an inability to remove additional soft tissue surrounding the prostate. Gleason sum 7 tumors had a significantly higher progression rate compared with Gleason sum 5 or 6 ones, although historically Gleason sum 5-7 lesions had been considered together as intermediate-grade tumors. In a multivariate analysis, positive margins and Gleason sum strongly correlated with progression, whereas capsular penetration did not. Only approximately 50% of patients with positive margins experienced disease progression during 5 years of follow-up. The most common single sites of positive margins were distal (22%), posterior (17%), and posterolateral (14%); 22% of positive margins were extensive. Only four patients (0.8% of the total) had positive margins only in the region of the spared neurovascular bundle and experienced progression. CONCLUSIONS: The most likely explanation for the discrepancy between margins and progression is that some of these margins represented artifactually positive margins caused by the unique problems with handling and assessing radical prostatectomy specimens. Radical prostatectomy provided excellent local control, with only 8% of patients exhibiting local recurrence. Sixty-one percent of men with progression had an elevated serum prostate-specific antigen level as their only manifestation of progression. The significance of isolated elevated serum prostate-specific antigen levels is uncertain, and long-term morbidity and mortality will depend on whether these patients have local disease or occult distant metastases.

Histological comparison of suction capsule and endoscopic small intestinal mucosal biopsies in children.

Small intestinal biopsies are part of the routine evaluation of children with chronic diarrhea and malabsorption, and are commonly performed via suction capsule. Because this technique entails x-ray exposure, longer procedure time, and technical failures, most small intestinal biopsies in adults are currently obtained via endoscopy. Endoscopy is believed to yield morphologically inferior specimens, and, therefore, its use for obtaining small intestinal biopsies in children has remained limited. The histological adequacy of biopsy specimens obtained in 30 children by endoscopy and in 30 children by suction capsule was compared. Biopsies were assessed for quality of orientation, size (length and depth), presence of Brunner's glands and crush artifact, and for the ability to confirm or exclude a mucosal abnormality. Small intestinal biopsies obtained via endoscopy were shown to yield tissue specimens that are histologically comparable to those obtained by suction capsule, and that are equally suitable for interpretation.