Introduction: Collecting duct carcinoma (CDC) is a rare, aggressive form of renal carcinoma that presents at an advanced stage and has a poor prognosis. Little is known concerning the optimal management of CDC. We present the results of a systematic review addressing the management of CDC and the McMaster University CDC series. Methods: The MEDLINE, Cochrane Library, and EMBASE databases and conference proceedings were searched to identify studies relating to the management of CDC. Included studies reported on a minimum of 10 subjects receiving a single intervention. Series in which an evaluation of therapeutic effectiveness was not possible were excluded. The McMaster University (Hamilton, Ontario) series of 6 cases of CDC were retrospectively reviewed. Results: We identified 3 studies relevant to the management of CDC that included a total of 72 patients. A gemcitabine–cisplatin or –carboplatin regimen resulted in a 26% objective response rate in 23 patients with metastatic CDC. Two additional studies indicated that 49 patients treated with immunotherapy achieved no response. In the McMaster series, cytoreductive nephrectomy was performed in 4 of 6 patients. In 2 patients, MVAC therapy (methotrexate–vinblastine–doxorubicin–cisplatin) achieved no response. No significant therapeutic complications occurred, but survival was poor (median: 11 months; range: 10–33 months). Conclusions: Our review and clinical experience suggest that the current standard of care for metastatic CDC is a gemcitabine–cisplatin regimen.
Prostate cancer metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention. In this study, we performed gene-expression profiling of prostate cancer stem-like cells (PCSC) derived from DU145 human prostate cancer cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a prostate cancer-promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. In addition, CNTN1 overexpression in DU145 cells and corresponding xenograft tumors resulted in elevated AKT activation and reduced E-cadherin (CDH1) expression. CNTN1 expression was not readily detected in normal prostate glands, but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with prostate cancer progression and worse biochemical recurrence-free survival following radical prostatectomy (P < 0.05). Collectively, our findings demonstrate that CNTN1 promotes prostate cancer progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies.
Background:Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated with prostate cancer (PC) remains unclear.Methods:ALDH3A1 expression was analysed in various PC cell lines. Xenograft tumours and 54 primary and metastatic PC tumours were stained using immunohistochemistry for ALDH3A1 expression.Results:In comparison with the non-stem counterparts, a robust upregulation of ALDH3A1 was observed in DU145-derived PC stem cells (PCSCs). As DU145 PCSCs produced xenograft tumours with more advanced features compared with those derived from DU145 cells, higher levels of ALDH3A1 were detected in the former; a dramatic elevation of ALDH3A1 occurred in DU145 cell-derived lung metastasis compared with local xenograft tumours. Furthermore, while ALDH3A1 was not observed in prostate glands, ALDH3A1 was clearly present in PIN, and further increased in carcinomas. In comparison with the paired local carcinomas, ALDH3A1 was upregulated in lymph node metastatic tumours; the presence of ALDH3A1 in bone metastatic PC was also demonstrated.Conclusions:We report here the association of ALDH3A1 with PC progression.
T he primary purpose of intraoperative pathologist consultation (IC) is to guide immediate surgical management;1 ICs can provide surgeons with important information that may be used to modify or even terminate a surgical procedure. Frozen sections performed during ICs can also be used Background: Correlation of intraoperative frozen section diagnosis with final diagnosis can be an important component of an institution's quality assurance process. Methods:We performed a quality assurance review of 1207 frozen section diagnoses from 812 surgical cases performed in the Hamilton Regional Laboratory Medicine Programme during a 6-month period in 2007. We reviewed the frozen section and permanent slides from all potentially discordant cases using a multiheaded microscope to arrive at a consensus pertaining to the type and reason for error. We reviewed the clinical record to determine whether there had been a potential adverse impact on immediate clinical management.Results: Frozen sections were most commonly requested for head and neck, nervous system and female genital tract specimens. Twenty-eight frozen sections (3%) were deferred. We identified 24 discordant diagnoses involving 3% of cases and 2% of specimens. The organ systems showing the greatest frequency of discordance relative to the total number from that system were the nervous system, head and neck, and the lungs. Of the errors identified, most occurred owing to diagnostic misinterpretation, followed by problems related to tissue sampling. There was a potential adverse impact on immediate clinical management in 14 cases.
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