Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter.

H+/peptide transporter, PEPT1, is functionally expressed in some human cancer cell lines and might be a candidate molecular target for detection of cancers in vivo using PET. The aim of the present study was to establish a novel tumor-imaging technology using a PET tracer targeted to H+/peptide transporter(s). We also compared the tracer with 18F-FDG, focusing on the specificity of their accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into athymic mice transplanted with human pancreatic, prostate, and gastric cancer cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing mice, and in mice with inflammatory tissue, were assessed by imaging with a positron planar imaging system (PPIS). Tissue distributions of tracer radioactivity were also measured. The expression levels of PEPT1 and PEPT2 (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58 available cancer cell lines were quantified by means of real-time polymerase chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of 11C-Gly-Sar increased in a time-dependent manner and were much higher than unity. Most of the radioactivity found in the tumor tissue was recovered as the intact tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG was highly accumulated, with the values of the selectivity index being >25.1 and 0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a promising tumor-imaging agent and is superior to 18F-FDG for distinguishing between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed in various types of tumor cells examined, 11C-Gly-Sar could be useful for the detection of many types of cancers.     

Risk factors for invasive aspergillosis in living donor liver transplant recipients.

Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P = 0.02) and preoperative steroid administration (P = 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT.     

Lymphoepithelioma-like carcinoma of the trachea.

Lymphoepithelioma is a lymphocyte-rich, poorly differentiated and non-keratinizing squamous cell carcinoma of the nasopharynx. Tumors arising outside the nasopharynx are rare and are designated as lymphoepithelioma-like carcinomas (LELCs). This is the third reported case of LELC of the trachea. A 27-year-old woman was referred to our hospital on suspicion of bronchial asthma on August 2000. A polypoid tumor of the cervical trachea was recognized on neck X-ray, neck computed tomography (CT) scan, and fiberoptic bronchoscopy. The protruding tumor was resected endoscopically by an electrosurgical snare. Histological and immunohistochemical examinations demonstrated large irregular polygonal cells extending in an islet or trabecular pattern among lymphoid stroma. These polygonal cells showed non-keratinization, atypia and prominent nucleoli. In situ hybridization showed these cells were infected with the Epstein-Barr (EB) virus. The infiltrating lymphocytes consisted of both T-and B-lymphocytes with no atypia. Thus the tumor was diagnosed as LELC. Blood examination revealed a past EB viral infection. Sphenoid resection of the tracheal cartilaginous portion was performed for residual tumor. We gave 50 Gy postoperative radiation, and she has been disease free in the 6-year follow-up period.     

A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.     

ENDOSCOPIC OBSERVATION OF MUCOSAL SPREAD LESION OF CHOLANGIOCARCINOMA USING PERORAL CHOLANGIOSCOPY WITH NARROW BAND IMAGING

A 69‐year‐old man was admitted to Toho University Omori Medical Center complaining of icterus. Abdominal computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were suspicious of cholangioma of inferior bile duct. Peroral cholangioscopy using narrow band imaging (NBI) was performed and it was possible to diagnose the mucosal spread lesions of cholangioma. Histological findings reflected the endoscopic findings. Mucosal spread lesions of cholangiocarcinoma were successfully diagnosed using the CHF‐B260 for NBI.     

A pilot study of the assessment of the quality of life, functional results, and complications in patients with an ileal neobladder for invasive bladder cancer

OBJECTIVE: To assess the functional results, health-related quality of life (QOL) outcomes, and complications in patients with an ileal neobladder in comparison to those with cutaneous diversion (ileal conduit and cutaneostomy). METHODS: Between September 1992 and February 2003, we consecutively performed an ileal neobladder (the Studer method) in 30 patients and cutaneous diversion in 38 patients. In August 2004, questionnaires were mailed to 54 patients. The questionnaire included the validated health-related quality of life (QOL) questionnaire, SF-36 General Health Survey, and a urinary incontinence questionnaire. We also evaluated the functional results in patients with an ileal neobladder and the postoperative complications in patients with both urinary diversions. RESULTS: The data from 41 patients (21 ileal neobladder procedures and 20 cutaneous diversions) were available for the analysis. No differences in the overall QOL were observed between the two groups. Complete daytime and night-time urinary continence was achieved in the 21 patients (100%) and 13 patients (61.9%), respectively. The mean value of the maximum flow rate was 15 +/- 12 mL/min in the 21 neobladder patients. There were 19 early complications in 18 patients (60.0%) and seven late complications in six patients (20.0%) with an ileal neobladder. However, there were 15 early complications in 14 patients (36.8%) and eight late complications in six patients (15.8%) with cutaneous diversions. CONCLUSION: The findings regarding the health-related QOL and the frequency of complications in the neobladder group and those in the cutaneous diversion group were similar. However, the functional results and the status of urinary continence in the neobladder patients were satisfactory.     

Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study

PURPOSE: To determine the effect of an interposition nerve graft on sexual function after radical prostatectomy. METHODS: This study includes 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted. Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the three groups. RESULTS: In the age-matched analysis, the postoperative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months postoperatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months postoperatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of comorbidities were different between the UNG and UNS groups. CONCLUSIONS: The difference of the SXF score between the UNG and UNS groups increased with time after 6 months postoperatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.     

Detection of urinary polyamine by a new enzymatic differential assay. (II). Comparison with conventional method

A new method of determining urinary polyamine concentration was compared with other techniques, namely, high pressure liquid chromatography (HPLC) and a polyamine test-enzyme kit. The values obtained by the new method, HPLC, and polyamine test-enzyme kit correlated well for all the fractions: diamine, spermidine and spermine. The correlation between the new method and the polyamine test-enzyme kit gave r = 0.9702, y = 1.1359x + 5.1266 (n = 48).