Sniffer mice discriminate urine odours of patients with bladder cancer: A proof-of-principle study for non-invasive diagnosis of cancer-induced odours.

Similar to fingerprints, humans have unique, genetically determined body odours. In case of urine, the odour can change due to variations in diet as well as upon infection or tumour formation. We investigated the use of mice in a manner similar to "sniffer dogs" to detect changes in urine odour in patients with bladder cancer. We measured the odour discrimination thresholds of mice in a Y-maze, using urine mixtures from patients with bladder cancer (Stage I) and healthy volunteers (dietary variations) as well as occult blood- or antibiotic drug metabolite-modulated samples. Threshold difference indicated that intensities of urinary olfactory cues increase in the following order: dietary variation < bladder cancer < occult blood < antibiotic drug metabolites. After training with patient urine mixtures, sniffer mice discriminated between urine odours of pre- and post-transurethral resection in individual patients with bladder cancer in an equal-occult blood diluted condition below the detection level of dietary variations, achieving a success rate of 100% (11/11). Furthermore, genetic ablation of all dorsal olfactory receptors elevated the discrimination thresholds of mice by ≥ 105-fold. The marked reduction in discrimination sensitivity indicates an essential role of the dorsal olfactory receptors in the recognition of urinary body odours in mice.

[Multi-institute survey on actual conditions of urologic management for severe bladder dysfunction after hysterectomy].

We conducted a multi-institute survey on the conditions related to urologic management of severe voiding dysfunction after hysterectomy for uterine cancer with or without postoperative irradiation. Our first study population was a group of adult female patients currently managed by urologists, using clean intermittent catheterization (CIC). Of the 287 patients in this group, 99 (34%) had suffered from uterine cancer. Of these patients, 94 underwent hysterectomy for this disease; 44 and 30 were treated with or without postoperative radiation, respectively, while postoperative irradiation status was unknown for 20. Median follow-up after surgery was 21 (0.2-52) years and median interval from operation to the introduction of CIC was 4.0 (0-49) years. CIC tended to be introduced later for patients with postoperative radiation than those without it. Seventy-four patients, who required invasive urologic interventions other than CIC for voiding dysfunction after hysterectomy, are the second study population. Most of these (82%) had received postoperative irradiation. Continuous Foley catheter placement was the most frequent procedure. Long-term follow-up and urologic management for voiding dysfunction is required for patients undergoing hysterectomy.

[A multi-center prospective study for antibiotic prophylaxis to prevent perioperative infections in urologic surgery].

In order to assess the ability of our protocol for antibiotic prophylaxis to prevent perioperative infections in urologic surgery, 1,353 operations of open and laparoscopic urologic surgery conducted in 21 hospitals between September 2002 and August 2003 were subjected to analyses. We classified surgical procedures into four categories by invasiveness and contamination levels: Category A; clean less invasive surgery, Category B; clean invasive or clean-contaminated surgery, Category C; surgery with urinary tract diversion using the intestine. Prophylactic antibiotics were administrated intravenously according to our protocol, such as Category A; first or second generation cephems or penicillins on the operative day only, Category B; first and second generation cephems or penicillins for 3 days, and Category C; first, second or third generation cephems or penicillins for 4 days. The wound conditions and general conditions were evaluated in terms of the surgical site infection (SSI) as well as remote infection (RI) up to postoperative day (POD) 30. The SSI rate highest (23.3%) for surgery with intestinal urinary diversion, followed by 10.0% for surgery for lower urinary tract, 8.9% for nephroureterctomy, and 6.0% for radical prostatectomy. The SSI rates in clean surgery including open and laparoscopic nephrectomy/adrenalectomy were 0.7 and 1.4%, respectively. In SSIs, gram-positive cocci such as methicillin-resistant Staphylococcus aureus (58.8%) or Enterobacter faecalis (26.5%) were the most common pathogen. Similarly, the RI rate was the highest (35.2%) for surgery using intestinal urinary diversion, followed by 16.7% for surgery for lower urinary tract, 11.4% for nephroureterctomy, and 7.6% for radical prostatectomy, while RI rates for clean surgery were less than 5%. RIs most frequently reported were urinary tract infections (2.6%) where Pseudomonas aeruginosa (20.3%) and Enterobacter faecalis (15.3%) were the major causative microorganisms. Parameters such as age, obesity, nutritional status (low proteinemia), diabetes mellitus, lung disease, duration of operation, and blood loss volume were recognized as risk factors for SSI or RI in several operative procedures. Postoperative body temperatures, peripheral white blood counts, C reactive protein (CRP) levels in POD 3 were much higher than those in POD 2 in cases suffering from perioperative infections, especially suggesting that CRP could be a predictable marker for perioperative infections.

Adenocarcinoma of the female urethral diverticulum treated by multimodality therapy.

A 75-year-old female presented with a 7-month history of intermittent macrohematuria and urinary retention. Physical examination revealed a firm, round mass on the anterior vaginal wall. The diagnosis by urethroscopy and radiological evaluation was localized urethral diverticular tumor. Pathological examination of the biopsy specimen revealed adenocarcinoma. The patient received two courses of intra-arterial and systemic chemotherapy using cisplatin, 5-fluorouracil and leucovorin, followed by radiation to the urethra. The tumor shrunk markedly after chemotherapy. The patient underwent total urethrectomy and vesicostomy. Two years after the operation, she had no evidence of recurrence. Adenocarcinoma of the female urethral diverticulum is rare and has been treated by surgery and/or radiation. The present case is the first case of it being treated by multimodality therapy including chemotherapy.

Significance of thymidylate synthase activity in renal cell carcinoma.

PURPOSE: 5-Fluorouracil (5-FU) is an anticancer agent clinically used against various cancers including renal cell carcinoma (RCC). 5-FU inhibits thymidylate synthase (TS) and blocks DNA synthesis. TS is the key enzyme in the catalysis of the methylation from dUMP to dTMP in the DNA synthetic process. Little is known about the significance of TS in RCC. We investigated the activity of TS in 68 RCCs and the association with dihydropyrimidine dehydrogenase (DPD) activities, which is a principal enzyme in the degradation of 5-FU and pyrimidine nucleotides. The relationship between TS/DPD activities in primary cultured RCC cell lines and their sensitivity to 5-FU was also examined. EXPERIMENTAL DESIGN: The levels of TS and DPD activities in nonfixed fresh-frozen RCC and normal kidney were determined biochemically by the 5-fluoro-2'-deoxyuridine 5'-monophosphate binding assay and the 5-FU degradation assay, respectively. The sensitivity of primary cultured RCC cells to 5-FU was assessed by the microculture tetrazolium dye assay. RESULTS: The activity of TS was approximately 5-fold higher in RCC compared with normal kidney. TS activity in T(3/4) RCC was 2.5-fold higher than that in T(1/2) RCC. TS activity in M(1) RCC was 2.5-fold higher than that in M(0) RCC. In addition, TS activity in stage III/IV RCC was 3-fold higher than that in stage I/II RCC. The levels of TS activity in grade 3 RCC were 3-fold and 2-fold higher than that in grade 1 and grade 2 cancer, respectively. TS activity in clear cell RCC were 4-fold higher than that in papillary RCC. Patients with low TS activity had a longer disease-specific survival as compared with those with high activity in the 5-year follow-up. There was no relationship between TS and DPD activities. TS activity in primary cultured RCC cells was positively correlated with their sensitivity to 5-FU. Furthermore, RCC cells with both high TS activity and low DPD activity were more sensitive to 5-FU, compared with those with either low TS activity or high DPD activity. CONCLUSIONS: The present study is the first study to demonstrate that the level of TS activity was correlated with both the progression of the stage and the increase of the grade of RCC, and that higher TS activity in primary cultured RCC predicted higher sensitivity to 5-FU. These results suggest that high TS activity may be associated with malignant potential of RCC, and that it may be possible to use 5-FU for RCC with high TS activity.