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.
The usefulness of the measurement of urinary lactoferrin (LF) released from polymorphonuclear leukocytes and of an immunochromatography test strip devised for measuring urinary LF for the simple and rapid diagnosis of urinary tract infections (UTI) was evaluated. Urine specimens were collected from apparently healthy persons and patients diagnosed as suffering from UTI. In the preliminary study, the LF concentrations in 121 normal specimens and 88 specimens from patients (60 with UTI) were quantified by an enzyme-linked immunosorbent assay. The LF concentration was 3,300.0 ± 646.3 ng/ml (average ± standard error of the mean) in the specimens from UTI patients, whereas it was 30.4 ± 2.7 ng/ml and 60.3 ± 14.9 ng/ml in the specimens from healthy persons and the patients without UTI, respectively. Based on these results, a 200-ng/ml LF concentration was chosen as the cutoff value for negativity. Each urine specimen was reexamined with the newly devised immunochromatography (IC) test strip to calculate the indices of efficacy. Based on the cutoff value, it was calculated that the sensitivity, specificity, and positive and negative predictive values of the IC test were 93.3, 89.3, 86.2, and 94.9%, respectively, compared with the results of the microscopic examination of the urine specimens for the presence of leukocytes. The respective indices for UTI were calculated as 95.0, 92.9, 89.7, and 96.6%. The tests were completed within 10 min. These results indicated that urine LF measurement with the IC test strip provides a useful tool for the simple and rapid diagnosis of UTI.
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.
Although prostate-specific antigen (PSA) is a significant tumor marker for prostate cancer at present, the
low specificity (approximately 33%) and so on likely lead to an overdiagnosis and patient suffering from
highly invasive prostate biopsy. Complementary measures with cancer-characteristic biomarkers could
improve the specificity and accuracy of diagnosis before the biopsy. Previously, “sniffer mice” were shown
to be super-sensitive to differences in odors and to discriminate between odors of urine mixtures from
patients with bladder cancer before and after tumor resection as well as urine odors of mice with or without
experimental tumors. Here, we showed that the sniffer mice discriminate efficiently urinary odors of patients
with prostate cancer using an odor plume-guided Y-maze behavioural assay. Through discrimination
training in forced-odor choice, statistically significant increases in correct odor choice rates showed the
super-sensitivity of sniffer mice to the olfactory cue of ppq-level urinary biomarkers for prostate cancer in
106
-fold diluted urine samples, where donor-unique odors were below the threshold. Moreover, we validated
eight volatile urinary biomarkers nearly at their original relative concentrations as the prostate cancer cue
even when adding a similar biomarker profile to the post-radical prostatectomy urine samples by the same
behavioural score of the sniffer mice. These biomarkers and profiles could be useful for non-invasive tests
for prostate and bladder cancers.
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