Munehisa Ueno

Differential Diagnosis of Primary Benign and Malignant Retroperitoneal Tumors

Background:

The Predictive Value of C-reactive Protein for Prognosis in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Multi-institutional Study

BACKGROUND Few studies have discussed the prognostic impact of serum C-reactive protein (CRP) level in upper tract urothelial carcinoma (UTUC). OBJECTIVE To investigate whether the perioperative level of CRP provides additional prognostic information following radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS A total of 564 patients with UTUC from a retrospective multi-institutional cohort were included. The median follow-up was 32 mo. INTERVENTION All patients underwent RNU without neoadjuvant chemotherapy, while 106 patients (18.8%) received adjuvant chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associations between perioperative CRP level and outcome were assessed using multivariate analysis. A serum CRP level >0.50mg/dl was defined as elevated. RESULTS AND LIMITATIONS Preoperative CRP (pre-CRP) level was elevated in 136 patients (24.1%). Multivariate analysis showed that pre-CRP elevation was an independent predictor of subsequent disease recurrence (hazard ratio [HR]: 1.47 for CRP 0.51-2.00; HR: 1.89 for CRP >2.00). Five-year recurrence-free survival rates were 69.2% in patients with pre-CRP levels ≤ 0.50 mg/dl, 54.3% in patients with pre-CRP levels between 0.51 and 2.00 mg/dl, and 35.4% in patients with pre-CRP levels >2.00 mg/dl (p<0.001). Similar results were found in cancer-specific mortality, showing that pre-CRP elevation was an independent predictor of worse outcome (HR: 1.74 for CRP 0.51-2.00; HR: 2.31 for CRP >2.00). In a subgroup analysis of the elevated pre-CRP group, postoperative normalisation of CRP level was an independent predictor of better outcome. This study is limited by its retrospective nature as well as its heterogeneous group of patients and variable follow-up protocols resulting from the multi-institution design. CONCLUSIONS Serum CRP may become a possible biomarker in UTUC, suggesting that patients with an elevated pre-CRP level could be predicted to have subsequent disease recurrence and cancer-specific mortality, while postoperative normalisation of CRP level was an independent predictor for prognosis.

Laparoscopic treatment of retroperitoneal benign schwannoma

Purpose/Methods: We report on a case of retroperitoneal benign schwannoma treated by laparoscopic surgery.

Ectopic thyroid in an adrenal mass: a case report

BackgroundIt is difficult to explain ectopic thyroid beneath the diaphragm because during the development the thyroid descends from the tongue to the anterior of the trachea. A few cases of ectopic lesions have been reported in the literature for abdominal organs including the adrenal glands, but the mechanism by which the thyroid components migrate into the abdomen has been poorly understood.Case presentationA 54-year-old woman was diagnosed as having an adrenal mass. Laparoscopic adrenalectomy was carried out. Microscopically, the mass was composed of normal adrenal and ectopic thyroid tissues.ConclusionWe herein describe the fourth case reported of ectopic thyroid in the adrenal gland.

Enhanced diagnostic accuracy for quantitative bone scan using an artificial neural network system: a Japanese multi-center database project

BackgroundArtificial neural network (ANN)-based bone scan index (BSI), a marker of the amount of bone metastasis, has been shown to enhance diagnostic accuracy and reproducibility but is potentially affected by training databases. The aims of this study were to revise the software using a large number of Japanese databases and to validate its diagnostic accuracy compared with the original Swedish training database.MethodsThe BSI was calculated with EXINIbone (EB; EXINI Diagnostics) using the Swedish training database (n = 789). The software using Japanese training databases from a single institution (BONENAVI version 1, BN1, n = 904) and the revised version from nine institutions (version 2, BN2, n = 1,532) were compared. The diagnostic accuracy was validated with another 503 multi-center bone scans including patients with prostate (n = 207), breast (n = 166), and other cancer types. The ANN value (probability of abnormality) and BSI were calculated. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) analyses were performed.ResultsThe ROC analysis based on the ANN value showed significant improvement from EB to BN1 and BN2. In men (n = 296), the area under the curve (AUC) was 0.877 for EB, 0.912 for BN1 (p = not significant (ns) vs. EB) and 0.934 for BN2 (p = 0.007 vs. EB). In women (n = 207), the AUC was 0.831 for EB, 0.910 for BN1 (p = 0.016 vs. EB), and 0.932 for BN2 (p < 0.0001 vs. EB). The optimum sensitivity and specificity based on BN2 was 90% and 84% for men and 93% and 85% for women. In patients with prostate cancer, the AUC was equally high with EB, BN1, and BN2 (0.939, 0.949, and 0.957, p = ns). In patients with breast cancer, the AUC was improved from EB (0.847) to BN1 (0.910, p = ns) and BN2 (0.924, p = 0.039). The NRI using ANN between EB and BN1 was 17.7% (p = 0.0042), and that between EB and BN2 was 29.6% (p < 0.0001). With respect to BSI, the NRI analysis showed downward reclassification with total NRI of 31.9% ( p < 0.0001).ConclusionIn the software for calculating BSI, the multi-institutional database significantly improved identification of bone metastasis compared with the original database, indicating the importance of a sufficient number of training databases including various types of cancers.

Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

BackgroundTypical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI) patients.Case presentationA male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: < 0.7 pmol/l (1.1 – 6.9); Parathyroid hormone-related protein (PTHrP): 2.3 pmol/l (0.7 – 1.8). Ultrasound scan of urinary bladder showed mixed echogenicity, which was diagnosed as debris. CT of pelvis was interpreted as vesical abscess. Urine cytology: Transitional cells showing mild atypia. Bladder biopsy: Inflamed mucosa lined by normal urothelial cells.A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later.ConclusionThis case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs.

SN-38 Induces Cell Cycle Arrest and Apoptosis in Human Testicular Cancer

OBJECTIVE CPT-11 is one of the most widely used camptothecin analogues and is converted to form the active metabolite SN-38. Clinical trials are ongoing to better characterize its spectra of clinical activity, to determine the optimal schedules of administration, and to define the usage in combination with other chemotherapeutic compounds. MATERIALS AND METHODS KU-MT, an AFP-producing testicular carcinoma cell line, was exposed to SN-38, etoposide, or cisplatin for 24 h, and the resulting cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay. This paper describes the effects of SN-38 on the cell proliferation and cell cycle of testicular tumor cells in culture. RESULTS SN-38 was shown to inhibit KU-MT cell growth more potently than either etoposide or cisplatin. A marked decrease in the percentage of S phase cells was accompanied by the enhancement of cyclin E levels. In concentrations of >30 nmol/l, SN-38 arrested the cell cycle in G2 and induced cell death via apoptosis. The apoptosis was promoted by Bax and p53 protein, which were both shown to be present by flow cytometric and Western blot analyses. CONCLUSION These results suggest that CPT-11, a pro-drug of SN-38, may be clinically useful for the treatment of testicular cancer, and that the mechanism of this agents cytotoxicity consists of cell cycle arrest and concomitant apoptosis.

Simultaneous production of granulocyte colony-stimulating factor and parathyroid hormone-related protein in bladder cancer

A case of bladder cancer with simultaneous production of granulocyte colony‐stimulating factor (G‐CSF) and parathyroid hormone‐related protein (PTHrP) is reported. An 81‐year‐old male patient was admitted to the Saitama Medical School for treatment of gross hematuria, leukocytosis and hypercalcemia and diagnosed as having advanced bladder cancer. Immediately after a cystectomy was carried out, his white cell count and serum calcium levels returned to normal. However, the tumors recurred locally and the recurrence was accompanied by an increase in the serum G‐CSF and PTHrP levels with a recurrent elevation of white cell count and the serum calcium level. The production of G‐CSF and PTHrP in the tumor cells was confirmed by immunohistochemistry.

The Impact of HIF1α on the Per2 Circadian Rhythm in Renal Cancer Cell Lines

In mammals, the circadian rhythm central generator consists of interactions among clock genes, including Per1/2/3, Cry1/2, Bmal1, and Clock. Circadian rhythm disruption may lead to increased risk of cancer in humans, and deregulation of clock genes has been implicated in many types of cancers. Among these genes, Per2 is reported to have tumor suppressor properties, but little is known about the correlation between Per2 and HIF, which is the main target of renal cell carcinoma (RCC) therapy. In this study, the rhythmic expression of the Per2 gene was not detectable in renal cancer cell lines, with the exception of Caki-2 cells. In Caki-2 cells, HIF1α increased the amplitude of Per2 oscillation by directly binding to the HIF-binding site located on the Per2 promoter. These results indicate that HIF1α may enhance the amplitude of the Per2 circadian rhythm.

Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A randomized, double-blind, multicentre phase II/III study.

BACKGROUND Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis. METHODS Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition. Effectiveness was evaluated by setting the primary endpoint to sensitivity. Safety was also analyzed. Moreover, clinically recommended doses of 5-ALA was also investigated as an investigator-initiated multicenter cooperative clinical trial in which five medical institutions participated. RESULTS All 62 enrolled patients completed the clinical trial. The sensitivities of PDD were higher (84.4 and 75.8% in the 10 and 20 m g/kg-groups, respectively) than those of conventional endoscopic diagnosis (67.5 and 47.6%, respectively) (p = 0.014 and p < 0.001, respectively). Five episodes of serious adverse events developed in four patients; whereas a causal relationship with the investigational agent was ruled out in all episodes. CONCLUSION This investigator-initiated clinical trial confirmed the effectiveness and safety of PDD for NMIBC following oral administration of 5-ALA. Both doses of 5-ALA may be clinically applicable; however, the rate of detecting tumors only by PDD was higher in the 20 mg/kg-group suggesting that this dose would be more useful.