Sunitinib is a multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma. However, sunitinib often causes hypothyroidism. In this study, we report eight cases with ...thyroid dysfunction that occurred during sunitinib treatment for advanced renal cell carcinoma. In seven cases, mild hypothyroidism developed early in the first treatment cycle, and recovered spontaneously. Transient hyperthyroidism was observed during the second or third treatment cycles and was preceded by a rapid increase in thyroglobulin levels. 99mTc scintigraphy in the hyperthyroid state showed decreased thyroidal uptake of 99mTcO4-, suggesting destructive thyroiditis. Hypothyroidism subsequently developed, requiring levothyroxine replacement therapy. Ultrasonography showed a hypoechogenic pattern of the parenchyma and decreased intrathyroidal blood flow. The thyroid glands ultimately became atrophic, which may progress to permanent hypothyroidism. These findings suggest that sunitinib-induced hypothyroidism may occur frequently and may be a consequence of thyroiditis with transient thyrotoxicosis. The marked decrease in thyroid size due to reduced capillary blood flow induced by VEGF receptor inhibition may cause delayed and/or permanent hypothyroidism. Therefore, thyroid function should be monitored in all patients treated with sunitinib.
We investigated the influence of nocturia and sleep disturbance on health-related quality of life(HRQOL) using the Medical Outcomes Study 8-item Short Form Health Survey (SF-8) in patients with ...nocturia. We also assessed the effect of therapeutic intervention by means of an anticholinergic agent on the results of the SF-8. One hundred and eighty-four patients who voided at least once per night were surveyed using the SF-8, Overactive Bladder Symptom Score (OABSS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). These parameters were also evaluated before and after 12 weeks of imidafenacin treatment in 51 patients with OAB accompanied by nocturia. The SF-8 physical component summary score (PCS) showed a significant decrease as nighttime voiding frequency increased. The mental health component summary score was 47.1 and 47.6 (which were lower than the standard value of 50) in the group with a nighttime frequency of once and ≥3/night, respectively. The SF-8 PCS and 6 subscales were negatively associated with nighttime voiding frequency, while the PSQI global score was positively associated with it. Imidafenacin significantly improved the OABSS, PSQI, and ESS, as well as the SF-8 score. This is the first study using the SF-8 to show that nocturia and sleep disturbance have a major influence on comprehensive HRQOL and that the SF-8 can be used to monitor HRQOL in OAB patients receiving treatment for nocturia.
To evaluate the safety and toxicity of peptide vaccination for patients with metastatic hormone‐refractory prostate cancer (HRPC) based on pre‐existing peptide‐specific cytotoxic T‐lymphocyte (CTL) ...precursors in the circulation, 10 patients positive for human leukocyte antigen (HLA)‐A2 with metastatic HRPC were enrolled in a phase I study. Peptide‐specific CTL‐precursors reactive to 16 kinds of vaccine candidates in the pre‐vaccination peripheral blood mononuclear cells (PBMCs) were measured, and patients were followed by vaccination with only positive peptides (up to 4 kinds of peptides). Serum prostate‐specific antigen (PSA) levels were monitored regularly. The peptide vaccination was safe and well tolerated with no major adverse effects. The most common toxicities were dermatologic reactions at the injection site. Increased CTL response to peptides was observed in 4 of 10 patients. Anti‐peptide IgG was also detected in post‐vaccination sera of 7 of 10 patients. One patient showed the disappearance of a pelvic bone metastasis after five vaccinations. Three patients showed a decrease of serum PSA level from the baseline after the vaccination, but no patients showed a serum PSA level decrease of ∼50%. The median survival duration of study patients was 22 months with follow‐up from 3 to 27 months. We consider that the increase in cellular and humoral immune responses, and decrease in PSA level in some patients justify further development of peptide vaccination for metastatic HRPC patients. (Cancer Sci 2004; 95: 77–84)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The aim of this study is to develop a novel experimental model of the subcutaneous transplantation of fetal urogenital sinus (UGS) into normal and castrated adult male rats for the pathophysiological ...investigation of the normal and developing prostate. Fetal UGS obtained from 20-day-old male rat embryos was subcutaneously transplanted into 7-week-old normal and castrated male rats. We observed the growth pattern, histopathological characteristics and immunohistochemical localization of cytokeratin 5 (CK 5), cytokeratin 8 (CK 8) and androgen receptor (AR) in the transplanted tissues. Almost all of the transplanted UGS organs gradually increased in weight over time in the non-castrated recipient animals, and the histopathological observations and immunohistochemical analysis of CK 5 and CK 8 revealed that the morphological changes in the tissues were in accordance with the features of normal prostate development. The histological characteristics included glandular epithelial dominant and stromal dominant area, with an increase in the glandular epithelial dominant areas over time and resemblance among a portion of the transplanted tissues within a certain period during the developmental course to the histopathology of human benign prostatic hyperplasia (BPH). The effects of androgens and resemblance in the immunohistochemical localization pattern changes in AR to that observed in the normal differentiating rat prostate were also noted. We conclude that the subcutaneous space provides an adequate microenvironment for UGS growth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
To analyze clinical and dosimetric factors involved in prostate‐specific antigen bounce in patients who underwent permanent implant brachytherapy for localized prostate cancer, and to study ...the relationships among prostate‐specific antigen bounce, age and sexual function.
Methods
Between March 2007 and April 2012, 116 patients with localized prostate cancer underwent permanent implant, iodine‐125 brachytherapy. Patients receiving external‐beam radiotherapy or who used phosphodiesterase‐5 inhibitor pre‐ or post‐treatment were excluded. Prostate‐specific antigen bounce was defined as an increase of ≥0.2 ng/mL and ≥0.4 ng/mL above an initial prostate‐specific antigen nadir followed by a subsequent decline to or below the initial nadir without treatment. Clinical and dosimetric factors involved in prostate‐specific antigen bounce were analyzed using multivariate logistic regression analysis with the forced entry method.
Results
The median age was 66 years (range 51–80 years), and prostate‐specific antigen bounce on a prostate‐specific antigen rise of ≥0.2 ng/mL occurred in 47 of the 116 participants (40.5%). The median period before the prostate‐specific antigen bounce was 17.5 months (range 8–36 months). Patients with prostate‐specific antigen bounce were younger and had higher sexual function before treatment (P = 0.003) than those who not show prostate‐specific antigen bounce. Regression analysis results showed that young age and a high level of pretreatment sexual function were significant predictive factors for prostate‐specific antigen bounce (P = 0.028 and P = 0.048).
Conclusion
Sexual function seems to be associated with a prostate‐specific antigen bounce in patients undergoing permanent implant brachytherapy for localized prostate cancer, and it can be preserved after treatment if it is well present before treatment. Highly maintained sexual function after treatment might influence prostate‐specific antigen bounce.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to investigate prognostic factors of patients with metastatic hormone refractory prostate cancer (HRPC) under combined administration of personalized peptide vaccination and ...low-dose estramustine phosphate (EMP). From February 2001 to July 2004, 58 men with metastatic HRPC received the combination therapy of personalized peptide vaccination and low-dose EMP. Conducted immune monitorings for those patients were peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production and peptide-reactive immunoglobulin G (IgG) by an enzyme-linked immunosorbent assay. Clinical responses and survival times were also evaluated. The combination therapy was well tolerated with no major adverse effects. Increased levels of CTL precursors and IgG responses to the vaccinated peptides were observed in 29 of 37 (78%) patients and in 36 of 41 (88%) patients tested, respectively. A prostate-specific antigen decline of at least 50% occurred in 24% of patients. The median survival time was 17 months (95% confidence interval, 12-25 months). Cox proportional hazards analysis showed that a low number of lymphocytes (p = 0.0075, odds ratio 2.700), a negative immunological activity response after the vaccination (p = 0.0185, odds ratio 2.658), and poor performance status (p = 0.0347, odds ratio 2.569) were independent predictors of disease death. These encouraging results show the need for further evaluation of the combination of personalized peptide vaccination and low dose of EMP for metastatic HRPC patients.
Aim: We investigated the feasibility and safety of the early removal of urethral catheters 3 days after radical retropubic prostatectomy.
Methods: Seventy consecutive patients underwent radical ...retropubic prostatectomy with the intent of early catheter removal on postoperative day (POD) 3. Catheter removal was based on postoperative cystograms performed on POD 2. Patients were analyzed using a validated prostate cancer specific questionnaire (University of California, Los Angeles Prostate Cancer Symptom Index) to determine quality of life outcomes. Multiple logistic regression analysis was also used to evaluate if any of the preoperative or intraoperative parameters were able to predict the success of early catheter removal after radical retropubic prostatectomy.
Results: The catheter was removed on POD 3 in 67 of 70 patients (97%) excluding three patients with moderate or severe extravasation on postoperative cystograms. Of the 67 patients, 53 (76%) were successful in early catheter removal, but the remaining 14 (24%) patients experienced urinary retention within 48 h and were treated with simple catheter replacement for 1 or 2 days. Two patients developed anastomotic strictures 3 and 4 months postoperatively, which were managed by dilation alone. Multiple logistic regression analysis showed that no leak during an intraoperative leak test was the only independent predictor of success for early catheter removal (P = 0.0069; odds ratio, 6.667; 95% confidence interval, 1.682–26.428).
Conclusion: The present study revealed that early catheter removal 3 days after radical retropubic prostatectomy is feasible in patients who show a negative intraoperative leak test. Postoperative monitoring of more patients is needed to determine if the early catheter removal is widely applicable.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Aim: We investigated whether the quantitative parameters of systematic sextant biopsies were predictive of either adverse pathological findings or disease recurrence after radical prostatectomy ...(RP).
Methods: We retrospectively evaluated a total of 117 men with untreated prostate cancer whose needle biopsies were matched with RP specimens. The pretreatment parameters of the serum prostate‐specific antigen (PSA), the PSA density, the percentage of positive biopsy cores, the percentage of cancer length and the percentage of Gleason grade 4/5 cancer in the biopsy were determined and compared with the pathological features of prostate cancer in RP specimens. These pretreatment parameters and pathological factors in the RP specimens, including the cancer volume, the percentage of Gleason grade 4/5 cancer, the positive surgical margin and the seminal vesicle invasion were evaluated for their ability to predict the disease recurrence.
Results: The percentages of positive biopsy cores, the Gleason grade 4/5 cancer in the biopsy and the cancer length in the biopsy had a weak correlation with the cancer volume in RP specimens (r = 0.373, 0.345, 0.408, respectively). All quantitative biopsy parameters were strongly predictive of the non‐organ‐confined status, the positive surgical margin and the seminal vesicle invasion in the logistic regression analysis. The percentage of positive biopsy cores and the percentage of Gleason grade 4/5 cancer in the biopsy predicted biochemical failure after RP.
Conclusion: These results indicate that quantitative biopsy parameters are independent predictors of the adverse pathology of prostate cancers and disease recurrence after RP.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
•We evaluated prognostic value of PD-1 and PD-L1 expression in metastatic RCC.•We also evaluated the relationship between these expression and intratumoral TILs.•PD-1 and PD-L1 expression was ...associated with adverse clinicopathological feature.•PD-1 and PD-L1 expression was associated with higher infiltration of TILs.•PD-1 expression has a significant worse impact on OS.
In renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC. The present study is aimed at evaluating the expression of PD-1 and PD-L1 and to investigate their clinical and prognostic significance in patients with clear cell RCC (CCRCC) having received molecular targeted therapies. In addition, we also evaluated the relationship between the expression of PD-1 and PD-L1 and intratumoral tumor infiltrating lymphocytes (TILs).
A total of 33 patients with metastatic CCRCC who underwent surgery and received molecular targeted therapies from March 2008 to April 2016 were retrospectively reviewed and analyzed. Tissue specimens from the patients were analyzed for PD-1 and PD-L1 expression by immunohistochemistry.
The median patient age was 64 years old (range=53-78). The majority of patients were male (81.8%). All Memorial Sloan Kettering Cancer Center risk groups were represented among the patients with 39.4% with favorable-, 51.5% with intermediate- and 9.1% with poor-risk. The expression of PD-1 and PD-L1 was observed in 16 (48.5%) and 9 (27.3%) patients, respectively. The expression of PD-1 and PD-L1 was associated with a larger primary renal tumor size, higher nuclear grade and sarcomatoid feature. Kaplan-Meier analysis revealed that no significant difference in progression free survival of first line molecular targeted therapy was found for PD-1 (P=0.2396) and PD-L1 (P=0.5919) expression. However, PD-1 expression has a significant worse impact on overall survival (OS) (P=0.0385), while for PD-L1 expression only a trend is seen for OS (P=0.1542). The patients with PD-1 and PD-L1 expression showed higher infiltration of CD4 (P<0.0001 and P<0.0001, respectively), CD8 (P=0.0328 and P=0.0044, respectively) and FOXP3 (P<0.0001 and P=0.0033, respectively) positive TILs.
PD-1 and PD-L1 expression is significantly associated with adverse clinicopathological features in CCRCC. Furthermore, PD-1 expression could be one of the biomarkers suggesting poor outcome in patients with metastatic CCRCC receiving molecular targeted therapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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