Three-dimensional mean stone density measurement is superior for predicting extracorporeal shock wave lithotripsy success.

OBJECTIVES: The objective of the present study was to investigate the usefulness of three-dimensional images of stones to measure mean stone density for predicting the outcome of shock wave lithotripsy. METHODS: We retrospectively identified 239 patients who underwent shock wave lithotripsy with pretreatment non-contrast computed tomography. We automatically measured the mean stone density of three-dimensional images of stones using a high-functional viewer. For comparison, mean stone density was also measured by two previously reported techniques using both the abdominal windows and the bone windows on the axial slice at the level of the largest diameter of the stone. We compared the outcome predictive power after the first treatment with outcomes according to measurement by four other methods. We also carried out logistic regression analysis, including mean stone density measured by three-dimensional images. RESULTS: The single treatment success rate was 48.5%. The effect size (14.148) of the mean stone density measured by three-dimensional images was higher than those of the other four manual methods. In addition, the area under the curve (0.6330) of the mean stone density measured by three-dimensional images was significantly higher than those of the other methods. Increasing stone volume (P = 0.002) and increasing mean stone density measured by three-dimensional images (P = 0.023) were significant independent predictors of the treatment outcome on multivariate analysis. CONCLUSIONS: This is the first study to compare the predictive powers for shock wave lithotripsy outcome of various mean stone density measuring methods. There is an indication that mean stone density automatically measured by three-dimensional images of stones is more useful than other measuring methods for predicting outcomes of shock wave lithotripsy.

Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1.

In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT-PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem-like cells.

Recurrent stone-forming patients have high visceral fat ratio based on computed tomography images compared to first-time stone-forming patients.

OBJECTIVES: To compare various fat parameters based on computed tomography images between recurrent stone-forming patients and patients forming stones for the first time. METHODS: Included in the present study were 300 patients with upper urinary tract calculi who had undergone active stone removal in our hospital. Using pretreatment computed tomography images, we measured visceral fat area and volume, subcutaneous fat area and volume, visceral fat area ratio and visceral fat volume ratio. We compared patient backgrounds and these fat parameters between those who recurrently formed stones and those who formed stones for the first time. We also performed logistic regression analysis to identify factors that contribute to severe stones. RESULTS: A total of 148 (49.3%) patients were recurrent stone-forming patients. Recurrent stone-forming patients were statistically significantly younger (P < 0.01) and there were more male patients (P < 0.01). In addition, visceral fat area ratio and visceral fat volume ratio in recurrent stone-forming patients were significantly higher than those in first-time stone-forming patients (P = 0.03 and P = 0.01, respectively). On the other hand, there was no significant difference in visceral fat area (P = 0.32), subcutaneous fat area (P = 0.36), visceral fat volume (P = 0.38) or subcutaneous fat volume (P = 0.23). Receiver operating characteristics analysis showed that area under the curve of visceral fat volume ratio (0.583) for recurrent stones was larger than that of visceral fat area ratio (0.571). In multivariate analysis, increasing visceral fat volume ratio was an independent significant predictor of recurrent stones (P = 0.04). CONCLUSIONS: Recurrent stone-forming patients have high visceral fat ratios compared to first-time stone-forming patients, shown here for the first time.

[A Case of Giant Testicular Tumor with Pelvic and Inguinal Lymph Nodes Metastasis].

A 51-year-old man visited our hospital since he had noticed remarkable increase in size of left scrotal contents. Computed tomography revealed left testicular swelling, retroperitoneal, pelvic and left inguinal lymph nodes. Serum testicular tumor markers (α fetoprotein, ß-human chorionic gonadotropin, lactate dehydrogenase) were elevated. Low left orchiectomy was performed due to swelling of the left inguinal lymph node. The excised specimen weighed 3,400g. Pathological findings were non-seminoma. Although there was no operation history of scrotal groin, there was metastasis in the left inguinal lymph node ; therefore, the stage of disease was T2N3M1a. According to the postoperative values of tumor markers, his condition was judged as "good prognosis" in the International Germ Cell Consensus Classification (IGCCC), and he underwent 3 courses of bleomycin, etoposide and cis-platin (BEP) therapy. Although the tumor markers decreased to the normal limit and the size of lymph node was remarkably decreased after 2 courses of BEP therapy, one course of EP therapy was added for further reduction of tumor size. For the residual lymph node metastasis, retroperitoneal lymph node dissection (RPLND) was performed. Then pelvic and left inguinal lymph node dissection was performed at a later date. Pathological findings of excised lymph nodes were only necrotic tissue. He is alive without disease recurrence three years after treatment.

Identification of antigenic peptides from novel renal cancer stem-like cell antigen, DNAJB8.

OBJECTIVES: To identify antigenic peptides of cancer stem-like cells (CSCs) antigen, DNAJB8, and establish a mouse CSCs-targeting immunotherapy model. MATERIALS AND METHODS: To induce DNAJB8-specific immune reaction, we stimulated human CD8+ lymphocytes with antigen-presenting cells pulsed with a cocktail of three candidate HLA-A*24:02 restricted peptides and assessed peptide specific human cytotoxic T lymphocytes (CTLs) induction. One of the antigenic peptides showed identical amino acid sequence as corresponding mouse DNAJB8. We evaluated CTL induction with the peptide immunization in mouse model. RESULTS: We confirmed peptide-specific interferon-γ secretions and cytotoxic activities of induced human CTLs. In vivo immunization with the peptide to mice, peptide-specific CTL response could be observed in mouse CD8+ T cells. Furthermore, immunization with the peptide showed significant anti-tumor effects compared with negative controls. CONCLUSION: DNAJB8-derived peptide is a novel candidate for CSCs-targeting immunotherapy, and mouse models can be used to evaluate CSCs-targeting immunotherapy.

Upper urinary tract stone disease in patients with poor performance status: active stone removal or conservative management?

BACKGROUND: It remains controversial as to whether active stone removal should be performed in patients with poor performance status because of their short life expectancy and perioperative risks. Our objectives were to evaluate treatment outcomes of active stone removal in patients with poor performance status and to compare life prognosis with those managed conservatively. METHODS: We retrospectively reviewed 74 patients with Eastern Cooperative Oncology Group performance status 3 or 4 treated for upper urinary tract calculi at our four hospitals between January 2009 and March 2016. Patients were classified into either surgical treatment group or conservative management group based on the presence of active stone removal. Stone-free rate and perioperative complications in surgical treatment group were reviewed. In addition, we compared overall survival and stone-specific survival between the two groups. Cox proportional hazards analysis was performed to investigate predictors of overall survival and stone-specific survival. RESULTS: Fifty-two patients (70.3%) underwent active stone removal (surgical treatment group) by extracorporeal shock wave lithotripsy (n = 6), ureteroscopy (n = 39), percutaneous nephrolithotomy (n = 6) or nephrectomy (n = 1). The overall stone-free rate was 78.8% and perioperative complication was observed in nine patients (17.3%). Conservative treatment was undergone by 22 patients (29.7%) (conservative management group). Two-year overall survival rates in surgical treatment and conservative management groups were 88.0% and 38.4%, respectively (p < 0.01) and two-year stone-specific survival rates in the two groups were 100.0% and 61.3%, respectively (p < 0.01). On multivariate analysis, stone removal was not significant, but was considered a possible favorable predictor for overall survival (p = 0.07). Moreover, stone removal was the only independent predictor of stone-specific survival (p < 0.01). CONCLUSIONS: Active stone removal for patients with poor performance status could be performed safely and effectively. Compared to conservative management, surgical stone treatment achieved longer overall survival and stone-specific survival.

Overexpression of ribonucleotide reductase subunit M1 protein predicts shorter survival in metastatic bladder cancer patients treated with gemcitabine-containing combination chemotherapy.

OBJECTIVES: To identify biomarkers predicting prognosis in bladder cancer patients undergoing the gemcitabine and cisplatin regimen. METHODS: We studied 52 patients with metastatic bladder cancer treated with the gemcitabine and cisplatin regimen by evaluating the relationship between the expression of two biomarkers, ribonucleotide reductase subunit M1 and excision repair cross complementing 1, by immunohistochemistry and clinical outcomes. RESULTS: The patients with low expression of ribonucleotide reductase subunit M1 showed a higher objective response rate by the gemcitabine and cisplatin regimen than those with high expression of ribonucleotide reductase subunit M1 (80.0% and 45.5%, respectively). No differences were observed according to the expression level of excision repair cross complementing 1. Low expression of ribonucleotide reductase subunit M1 significantly prolonged overall survival and progression-free survival compared with the high expression group. Low expression of excision repair cross complementing 1 tended to prolong overall survival and progression-free survival, but there were no significant differences (P = 0.07 and 0.10, respectively). Multivariate analysis showed that the expression of ribonucleotide reductase subunit M1 was the only independent prognostic factor (P = 0.012). CONCLUSIONS: The expressions of ribonucleotide reductase subunit M1 seem to be associated with clinical response and survival in patients with metastatic bladder cancer treated with gemcitabine and cisplatin-based chemotherapy.

[A Case of Long-Term Survival after Combination Therapy for Gastric Cancer with Synchronous Multiple Liver Metastasis].

A 63-year-old man was admitted to our hospital owing to weight loss and vertigo. Endoscopic examination revealed advanced gastric cancer type 2. Abdominal CT showed a 62mm liver tumor in segment 4 and a 26mm tumor in segment 8. Distal gastrectomy and D2 lymph node dissection were performed. After surgery, he was administered chemotherapy with S- 1. After 2 courses of treatment, the tumors' in segments 4 and 8 were reduced to 52mm and 16mm, respectively. No other metastases were detected. Left lobectomy and partial resection of segment 8 were performed. The pathological therapeutic effects were rated as Grade 1b for the tumor in segment 4 and Grade 3 for the tumor in segment 8. After hepatectomy, he was administered adjuvant chemotherapy with S-1 for 1 year. No recurrence has been detected for 4 years and 6months after hepatectomy.

Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.

The aim of the present study was to establish cancer stem-like cell/cancer-initiating cell (CSC/CIC)-targeting immunotherapy. The CSC/CIC are thought to be essential for tumor maintenance, recurrence and distant metastasis. Therefore they are reasonable targets for cancer therapy. In the present study, we found that a heat shock protein (HSP) 40 family member, DnaJ (Hsp40) homolog, subfamily B, member 8 (DNAJB8), is preferentially expressed in CSC/CIC derived from colorectal cancer (CRC) cells rather than in non-CSC/CIC. Overexpression of DNAJB8 enhanced the expression of stem cell markers and tumorigenicity, indicating that DNAJB8 has a role in CRC CSC/CIC. A DNAJB8-specific cytotoxic T lymphocyte (CTL) response could be induced by a DNAJB8-derived antigenic peptide. A CTL clone specific for DNAJB8 peptide showed higher killing activity to CRC CSC/CIC compared with non-CSC/CIC, and CTL adoptive transfer into CRC CSC/CIC showed an antitumor effect in vivo. Taken together, the results indicate that DNAJB8 is expressed and has role in CRC CSC/CIC and that DNAJB8 is a novel target of CRC CSC/CIC-targeting immunotherapy.

External validation of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment scoring models to predict recurrence and progression in Japanese patients with non-muscle invasive bladder cancer treated with bacillus Calmette-Guérin.

OBJECTIVE: To validate two prediction models (European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment) for recurrence and progression of non-muscle invasive bladder cancer in Japanese patients who underwent bacillus Calmette-Guérin instillation therapy. METHODS: From March 1985 to April 2007, data were analyzed from 366 patients who underwent transurethral resection of bladder tumor followed by bacillus Calmette-Guérin instillation therapy. The ability of two scoring models to predict recurrence and progression was assessed by concordance index. RESULTS: For recurrence probability, the concordance index of the European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.514 and 0.576, respectively, which was lower than that (0.604) of a selected single prognostic factor (age) by our multivariate analysis. For progression probability, the concordance index of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.693 and 0.764, respectively, which was higher than that (0.633) of a selected single factor (T stage) by our multivariate analysis. The Spanish Urological Club for Oncological Treatment scoring system resulted in better stratification of tumor recurrence and progression when compared with the European Organization for Research and Treatment of Cancer model, probably because more patients underwent bacillus Calmette-Guérin treatment in the Spanish Urological Club for Oncological Treatment cohort than in the European Organization for Research and Treatment of Cancer cohort. CONCLUSIONS: The Spanish Urological Club for Oncological Treatment scoring system is a good predictor of tumor recurrence and progression in Japanese patients who underwent bacillus Calmette-Guérin immunotherapy. A large prospective study is warranted to confirm the efficacy of this system.

Docetaxel in combination with estramustine and prednisolone for castration-resistant prostate cancer.

BACKGROUND: The aim of this study was to investigate the efficacy and toxicity of docetaxel-based chemotherapy, and to investigate pretreatment factors that can predict overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). METHODS: From June 2005 to July 2010, 70 patients with CRPC underwent docetaxel-based chemotherapy at Wakayama Medical University and related hospitals. Docetaxel was given at a dose of 70 mg/m(2) once every 3 weeks or 35 mg/m(2) twice every 3 weeks. Oral estramustine 560 mg was given concurrently for five consecutive days during weeks 1 and 2 of each cycle, and prednisolone 10 mg was given every day. Dexamethasone 8 mg was premedicated intravenously before docetaxel administration. RESULT: The patients received a median of four cycles of treatment (range 1-31). In the serum prostate-specific antigen response, 13 (18.6%) patients achieved a complete response and 29 (41.4%) achieved a partial response. Median OS and time to progression were 14 months and 6 months, respectively. Median follow-up period was 9.5 months. Two independent pretreatment risk factors that predicted OS were visceral metastasis including lymph node metastasis and anemia. Grade 3/4 neutropenia and anemia occurred in 25.7 and 8.6% of the patients, respectively. Four treatment-related deaths were seen during the observation period. CONCLUSION: The combination of docetaxel, estramustine and prednisolone was effective in Japanese patients with CRPC; however, this combination therapy should be carefully indicated to elderly and/or poor performance status patients due to its toxicity. Visceral metastasis and anemia were identified as independent risk factors which could predict OS.

[A case of collecting duct carcinoma originating from renal cyst].

In December 2003, a 32-year-old man underwent puncture for right renal cyst at a clinic. Since puncture fluid was dark red color in spite of negative cytology, he was being followed, but after a while he did not show up for further examination. In November 2007, he revisited the clinic due to low-grade fever. Computed tomographic findings showed an enlarged cystic mass with a solid component invading the liver and lymph node swelling. He underwent right radical nephrectomy combined with partial liver resection and lymphadenectomy. Histological findings showed collecting duct carcinoma associated with clear cell carcinoma directly invading the liver with lymph node metastasis (pT4N2M0). Although he underwent 4 cycles of gemcitabine-cisplatin therapy and alfa interferon injection 3 times a week thereafter as adjuvant setting, multiple liver metastasis occurred 15 months after surgery. He died of cancer 31 months after surgery in spite of molecular targeted therapy including sorafenib and sunitinib.

Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells.

Cancer stem-like cells (CSCs) and tumor-initiating cells (TICs) are a small population of cancer cells that share three properties: tumor initiating ability, self-renewal, and differentiation. These properties suggest that CSCs/TICs are essential for tumor maintenance, recurrence, and distant metastasis. Here, we show that cytotoxic T lymphocytes (CTLs) specific for the tumor-associated antigen CEP55 can efficiently recognize colon CSCs/TICs both in vitro and in vivo. Using Hoechst 33342 dye staining, we isolated CSCs/TICs as side population (SP) cells from colon cancer cell lines SW480, HT29, and HCT15. The SP cells expressed high levels of the stem cell markers SOX2, POU5F1, LGR5, and ALDH1A1 and showed resistance to chemotherapeutic agents such as irinotecan or etoposide.To evaluate the susceptibility of SP cells to CTLs, we used CTL clone 41, which is specific for the CEP55-derived antigenic peptide Cep55/c10orf3_193 (10) (VYVKGLLAKI). The SP cells expressed HLA class I and CEP55 at the same level as the main population cells. The SP cells were susceptible to CTL clone 41 at the same level as main population cells. Furthermore, adoptive transfer of CTL clone 41 inhibited tumor growth of SW480 SP cells in vivo. These observations suggest that Cep55/c10orf3_193(10) peptide-based cancer vaccine therapy or adoptive cell transfer of the CTL clone is a possible approach for targeting chemotherapy-resistant colon CSCs/TICs.

Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population.

The aim of this study was to establish a novel efficient cancer DNA vaccine approach. Many tumor-associated antigens (TAAs) have been reported; however, there is little information of the efficiency of each TAA. Normal cells barely undergo mitosis, whereas cancer cells divide frequently and grow well. Thus, G2/M-related antigens are cancer cell-specific and are regarded to be suitable candidates as targets of cancer immunotherapy. In this study, we compared the efficiencies of G2/M-related antigens including Birc5, Aurka, Nke2 and Plk1 by using a DNA vaccination model. Mice that had been immunized with G2/M-related antigens coding plasmid were challenged with CT26 colon cancer cells. Interestingly, Birc5- and Aurka-immunized mice showed an anti-tumor effect, whereas Nek2- and Plk1-immunized mice did not show any anti-tumor effect. We investigated the expression of G2/M-related antigens in cancer stem-like cell (CSC)/cancer-initiating cell (CIC) population to verify the difference in the anti-tumor effect. CSCs/CICs were isolated as side population (SP) cells using Hoechst 33342 dye from CT 26 cells. It was found that Birc5 and Aurka are expressed in both CSCs/CICs and non-CSCs/CICs (shared antigens), whereas Nek2 and Plk1 are expressed preferentially in non-CSCs/CICs (non-CSC antigens). Therefore, antigen expression in the CSC/CIC population might be related to the anti-tumor efficiency of cancer immunotherapy. Furthermore, we established a heat shock protein (Hsp90)-fused Birc5 plasmid to improve anti-cancer immunity. Birc5 fused to the N-terminal region of Hsp90 showed a stronger anti-tumor effect, whereas Birc5 fused to the C-terminal region of Hsp90 did not show enhancement compared with Birc5. These observations indicate that expression in the CSC/CIC population is essential to achieve tumor regression and that fusing antigens to the N-terminal region of Hsp90 enhances the anti-tumor effect.

[Laparoscopic pyelolithotomy in a horseshoe kidney].

A 66-year-old woman had a 22 mm right kidney stone accompanied with a horseshoe kidney. The size of this stone had been increasing gradually from 7 mm to 22 mm during the past 5 years. Although apparent pelviuretic junction stenosis could not be identified by intravenous urography, external pelvis was dilated in both kidneys. Complete excretion of fragmented stones by extracorporeal shockwave lithotripsy seemed to be difficult because impaired urinary passage from the renal pelvis to the ureter was suspected. Percutaneous nephrolithotomy was also difficult due to malrotation of the pelvic-caliceal system and possible interposition of bowel loops between kidney and abdominal wall. Therefore, we chose laparoscopic pyelolithotomy. This procedure made it possible to remove the stone completely with minimum invasiveness. We assume that laparoscopic pyelolithotomy is a safe and effective approach for renal pelvic stone in case of horseshoe kidney.

Insulin resistance increases the risk of urinary stone formation in a rat model of metabolic syndrome.

OBJECTIVE: To investigate the association between metabolic syndrome and urinary stone disease, and whether insulin resistance associated with adiposity affects the risk of urinary stone formation, using a rat model of metabolic syndrome. MATERIALS AND METHODS: Four-week-old male Otsuka Long-Evans Tokushima 'Fatty' (OLETF, a model of human type 2 diabetes and metabolic syndrome) rats, and Long-Evans Tokushima (LETO, a non-diabetic control) rats (10 each) were given a standardized diet and free access to water. Body weight and serum and urinary biochemistry were determined every 4 weeks. Ten-week-old male OLETF and LETO rats were divided into three groups of nine each and treated with vehicle or oral administration of 3 or 10 mg/kg/day pioglitazone, an agent that improves insulin resistance. After 4 weeks, body weight and serum and urinary biochemistry were determined. RESULTS: The OLETF rats had significantly lower urinary pH and citrate excretion, and higher urinary uric acid and calcium excretion, than the LETO rats, with increases in body weight, serum triglyceride, glucose and insulin. The administration of pioglitazone to the OLETF rats for 4 weeks significantly increased urinary pH dose-dependently. There was no change in the urinary excretion of citrate, uric acid, calcium, oxalate or magnesium. CONCLUSION: These results indicate that metabolic syndrome causes the changes in urinary constituents, leading to increased risk of both uric acid and calcium stone formation. Improvement in insulin resistance, a central cause of metabolic syndrome, might prevent uric acid stone formation by raising urinary pH.

[Extra-adrenal pheochromocytoma with the manifestation of catecholamines cardiomyopathy: a case report].

A 22-year old female had an episode of acute heart and respiratory failure requiring mechanical ventilation ducing a trip overseas. Echocardiography demonstrated akinesis of the apical area (left ventricle ejectionfraction(LVEF) =15%). Since computed tomography (CT) with coronary angiography to rule out acute coronary syndrome showed no abnormalities, she was diagnosed with morphological stress cardiomyopathy due to akinesis of the apical area. After returning to Japan, she was admitted to our hospital for further examination. She had an increased level of catecholamines in 24-hour urine. ¹³¹Imetaiodobenzyguanidine scintigraphy, CT scan and fluorodexyglucose positron emission tomography revealed a retroperitoneal mass. From these results, a diagnosis of extra-adrenal pheochromocytoma with catecholamine-induced cardiomyopathy was made. Histological diagnosis of the laparoscopically resected tumor was pheochromocytoma. After the operation, the level of catecholamines in 24-hour urine was normalized.

Ureteral wall volume at ureteral stone site is a critical predictor for shock wave lithotripsy outcomes: comparison with ureteral wall thickness and area.

Our objectives were to compare measurements of ureteral wall area, ureteral wall volume and ureteral wall thickness for their use in prediction of shock wave lithotripsy outcomes. We retrospectively identified 218 patients that underwent shock wave lithotripsy for ureteral calculi with pretreatment non-contrast computed tomography. We measured ureteral wall thickness, ureteral wall area and ureteral wall volume by high functional viewer. Ureteral wall thickness was defined as the maximum thickness of ureteral wall, and ureteral wall area as the area of ureteral wall around the stone in the maximal stone diameter on axial computed tomography image. Ureteral wall volume was defined as the volume of ureteral wall from the upper to lower edge of the stone. Treatment success was defined as absence of residual fragments within 3 months after the first session. We compared the outcome predictive power among these parameters and logistic regression analysis to identify factors contributing to treatment failure. The treatment success rate was 47.6%. Ureteral wall thickness, ureteral wall area and ureteral wall volume in successful cases were all significantly smaller than those in unsuccessful cases (all p < 0.01). Area under curve of ureteral wall volume was the largest of these parameters and significantly larger than that of ureteral wall thickness (p < 0.01). On multiple logistic regression analysis, ureteral wall volume was the only significant independent predictor of treatment outcome. Ureteral wall volume is a better predictor of shock wave lithotripsy outcome than ureteral wall thickness or ureteral wall area.

Myosteatosis as a novel prognostic biomarker after radical cystectomy for bladder cancer.

This study aims to evaluate the influence of myosteatosis on survival of patients after radical cystectomy (RC) for bladder cancer. We retrospectively identified 230 patients who underwent RC for bladder cancer at our three institutions between 2009 and 2018. Digitized free-hand outlines of the left and right psoas muscles were made on axial non-contrast computed tomography images at level L3. To assess myosteatosis, average total psoas density (ATPD) in Hounsfield Units (HU) was also calculated as an average of bilateral psoas muscle density. We compared cancer-specific survival (CSS) between high ATPD and low ATPD groups and performed cox regression hazard analyses to identify the predictors of CSS. Median ATPD was 44 HU (quartile: 39-47 Hounsfield Units). Two-year CSS rate in overall patients was 76.6%. Patients with low ATPD (< 44 HU) had significantly lower CSS rate (P = 0.01) than patients with high ATPD (≥ 44 HU). According to multivariate analysis, significant independent predictors of poor CSS were: Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.03), decreasing ATPD (P = 0.03), non-urothelial carcinoma (P = 0.01), pT ≥ 3 (P < 0.01), and pN positive (P < 0.01). In conclusion, myosteatosis (low ATPD) could be a novel predictor of prognosis after RC for bladder cancer.

Bacillus Calmette-Guérin cell-wall skeleton enhances the killing activity of cytotoxic lymphocyte-activated human dendritic cells transduced with the prostate-specific antigen gene.

UNLABELLED: To determine whether dendritic cells (DC) transduced with the prostate-specific antigen (PSA) gene can induce PSA-specific cytotoxic lymphocytes (CTL) against prostate cancer cells, and whether bacillus Calmette-Guérin (BCG) cell-wall skeleton (CWS) can enhance the maturation of DC-PSA and the killing activity of subsequently induced PSA-specific CTL. MATERIALS AND METHODS; We generated an adenovirus encoding the PSA gene (AxCA-PSA) using the cosmid-terminal protein complex method. DC were infected with AxCA-PSA using the centrifugal method. The ability of CTL to lyse target cells expressing PSA, i.e the PSA-positive prostate cancer cell line, LNCap, and PSA-transduced autologous phytohaemagglutinin (PHA) blasts expressing PSA, was assessed using the 51Cr-release assay. The maturation of DC-PSA stimulated by BCG-CWS was assayed by flow cytometry. The cytotoxic activity enhanced by BCG-CWS was assessed by the 51Cr-release assay. RESULTS: DC-PSA induced PSA-specific CTL with 85% cytotoxic activity against LNCaP (effector: target ratio, E:T, of 50:1). However, the cytotoxic activity against PSA-negative cells was very low. Anti-CD8 and anti-major histocompatibility (MHC) class I antibodies blocked PSA-specific cytotoxicity. The PSA-specific killing was reproducible against autologous PHA blast cells expressing PSA, independently of human leukocyte antigen haplotype. Furthermore, the combination of DC-PSA with BCG-CWS remarkably enhanced the PSA-specific cytotoxicity against PHA blasts expressing PSA (15-30% at an E:T ratio of 50:1). CONCLUSION: These findings suggest that DC-PSA can induce MHC class I-restricted PSA-specific CD8+ CTL responses and that DC-PSA matured by BCG-CWS enhance PSA-specific cytotoxicity. The combination of DC-PSA with BCG-CWS might be a useful approach for treating advanced prostate cancer.