Naoki Kawamura

Identification of a 1-cM Region of Common Deletion on 4q35 Associated With Progression of Hepatocellular Carcinoma

To identify the location of one or more of the putative tumor suppressor genes (TSG) on chromosome arm 4q that may be involved in hepatocellular carcinoma (HCC), we examined 96 primary HCCs for their patterns of allelic loss at 39 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 71 (74%) HCCs. Detailed deletion mapping identified two distinct commonly deleted regions; one was located within a 1‐cM interval flanked by D4S1534 and D4S2929 at 4q21–22, the other in the 1‐cM interval flanked by D4S2921 and D4S2930 at 4q35. Of the tumors for which clinical data were available, allelic loss at 4q35 was more frequent in poorly or moderately differentiated tumors than in well‐differentiated tumors (3/15, 20%, vs. 14/21, 67%, P = 0.008); in tumors larger than 2 cm in size (2/11, 18%, vs. 34/62, 55%, P = 0.046); and in tumors that arose from liver cirrhosis as opposed to HCCs arising from chronic hepatitis (25/42, 60%, vs. 9/27, 33%, P = 0.048). The association of allelic losses on 4q35 with larger tumor size and aggressive histological type implies that loss or inactivation of TSG located within the 1‐cM interval of 4q35 identified here contribute to progression of HCCs. Genes Chromosomes Cancer 25:284–289, 1999.

PTEN/MMAC1 mutations in hepatocellular carcinomas: somatic inactivation of both alleles in tumors.

Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1‐bp insertion at codon 83–84 in exon 4 and two 4‐bp deletions, both at codon 318–319 in exon 8; two C‐to‐G transversion mutation, both at ‐9 bp from the initiation codon in the 5’non‐coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors.

Identification of a 1-Mb common region at 16q24.1-24.2 deleted in hepatocellular carcinoma.

To identify the location of one or more putative tumor suppressor genes that may be involved in hepatocellular carcinoma (HCC), we examined 96 such tumors for their patterns of allelic loss at 21 microsatellite marker loci distributed along chromosome arm 16q. Allelic loss at one or more loci was observed in 58 (60%) of these tumors. Detailed deletion mapping identified a distinct commonly deleted region located within an interval flanked by D16S534 and D16S3091 at 16q24.1–24.2. By constructing a physical map consisting of a YAC contig across the region, the extent of the deleted region was determined to be less than 1 Mb. Among the tumors for which clinical data were available, allelic loss at 16q24.1–24.2 was more frequent in tumors arising from liver cirrhosis compared to HCCs arising from chronic hepatitis (30/42, 71%, vs. 13/33, 39%; P = 0.0054). Additionally, allelic loss at 16q24.1–24.2 was frequently observed in small tumors and early‐stage tumors as well as in tumors of more advanced phenotype. Genes Chromosomes Cancer 28:38–44, 2000.

Clinical Application of Video Image Flexible Ureteronephroscope for Diagnosis of Upper Urinary Tract Disorders

Ureteroscopy has become the diagnostic and therapeutic procedure of choice for many conditions of the upper urinary tract. Technology is progressing rapidly in endourology, facilitating both goals. As reported previously, we developed a 2F video image flexible ureteronephroscope. This instrument is the smallest caliber of all ureteronephroscopes available to date. Because of the small diameter the device can be inserted into the ureter cystoscopically in a manner similar to catheter insertion. The procedure is done with the patient under local anesthesia. We performed ureteronephroscopic procedures on 79 patients using mainly a 6F passively deflecting flexible ureteronephroscope, which consists of the aforementioned 2F video image flexible ureteronephroscope and a 3F working channel. The area to be viewed was accessed successfully in 41 of 43 patients (95%). Over-all, diagnostic maneuvers were successful in 64 of 79 patients (87%). We suggest that the 2F and 6F flexible ureteronephroscopes would be indicated when conclusive diagnosis for upper urinary disease is not obtained by other means.

Is it safe to continue antithrombotic agents before prostate biopsy

Background Whether antithrombotic agents should be stopped before prostate biopsy is unsettled. We investigated the impact of antithrombotic agents on bleeding complications after prostate biopsy. Materials and methods Among the patients who underwent transrectal ultrasound-guided prostate biopsy from June 2006 to December 2013 at Ebina General Hospital, Kanagawa, Japan, 1817 cases were retrospectively assessed. Patients were divided into two groups: those not taking antithrombotic agents (control group) and those taking them (experimental group). The frequency and severity of bleeding complications after the procedure were compared. The severity of bleeding events was graded using the Common Terminology Criteria for Advanced Events vol. 4.0. Results Hemorrhagic complications were classified into grades 1 to 3. Patients with complications of Grade 2 and above needed treatment. As for the Grade 1 event, there were no differences between two groups. The frequency of more than Grade 2 bleeding events was 1.7% and 3.5% in the control and experimental group, respectively; the odds ratio was 2.18 (P = 0.039). Grade 3 events occurred in seven patients of the control group (0.5%) and four patients of the experimental group (1.2%). Conclusions The present study showed that continuation of antithrombotic agents increased the frequency of hemorrhagic complications requiring intervention. It suggests that attention should be paid to the patients taking antithrombotic agents before prostate biopsy.

MP77-02 THE ANTITHROMBOTIC AGENTS DO NOT NEED TO DISCONTINUE PRIOR TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BIOPSY: A SINGLE CENTER EXPERIENCE.

INTRODUCTION AND OBJECTIVES: The natural history of prostatic lesions identified on multiparametric MRI (mpMRI) is unknown. We aimed to describe changes observed over time on serial mpMRI, and to determine especially how these influenced management of men on active surveillance (AS). METHODS: Between January 2008 and October 2014, 754 men underwent mpMRI, of whom 65 had 2 studies. Imaging findings and corresponding clinico-pathologic parameters were compared and related to the discontinuation of AS. RESULTS: Serial mpMRIs were performed for AS monitoring in 42 men and for suspicion of prostate cancer in 23 men. Collectively, there were 93 lesions on 1st mpMRI and 143 on 2nd mpMRI for analysis. The median time between scans was 19.7 months (IQR 13.529.5). New lesions were seen in 34 of 65 (52.3%) patients. The Median (IQR) number of lesions seen per patient increased from 1 (1-2) to 2 (13). Lesion size increased in 29.4% (mean 3.0 mm/yr) and decreased in 18.5% (mean -2.1mm/yr ). The ADC value decreased in 47.9 % of lesions (>300 unit decrease in 15%) between scans and increased in a further 25 %. Three of 47 (6%) lesions moved from ADC>600 to ADC <600. Forty-nine (53%) lesions were scored PIRADS 3 on first MRI, of which 5 (10%) converted to PIRADS 4. There were 21 de novo PIRADS 4/5 lesions identified in 15 patients (23%). Overall, 10 (24.3%) men on AS chose to undergo definitive therapy following an increase in suspicion of cancer on their MRI. Eight of the 10 men were confirmed to have pathological progression on biopsy. Four of these developed a new PIRADS 4 lesion, and 2 had conversion of PIRADS 3 to PIRADS 4. Two additional patients had an increase in lesion size between scans. CONCLUSIONS: In general, serial mpMRI demonstrates small changes in lesion appearance over time. However, new lesions are common, and changes in lesion characteristics between MRIs significantly influenced the management of men on AS.