Assistent guide short: A new device for facilitating ureteric stenting in women.


Lymph node dissection during radical cystectomy for bladder cancer: A two-center comparative study of robotic versus open surgery.

This study was performed to evaluate the safety and efficacy of lymph node dissection (LND) during robot-assisted radical cystectomy (RARC) compared with open radical cystectomy (ORC). From October 2003 to December 2021, 122 patients underwent LND during RARC and 103 patients underwent LND during ORC at Tokushima University Hospital and Tokushima Prefectural Central Hospital. We investigated the safety and efficacy of LND during RARC by comparing the surgical and oncological outcomes between the two groups. The patients were significantly older in the RARC than the ORC group. The operative time was significantly shorter and the estimated blood loss was significantly lower in the RARC than the ORC group. Although the lymph node yield was significantly higher in the RARC than the ORC group, there was no significant difference in lymph node positivity between the groups. There was no significant difference in the incidence of local recurrence or distant metastasis between the two groups. The 5-year survival rates (overall survival, cancer-specific survival, and recurrence-free survival) were not different between the RARC and ORC groups. This study suggests that the surgical and oncological safety and efficacy of LND during RARC are greater than those of LND during ORC. We believe that LND during RARC is a higher-quality procedure than LND during ORC.


Insulin receptor expression to predict resistance to axitinib and elucidation of the underlying molecular mechanism in metastatic renal cell carcinoma.

Decreased INSR in RCC could be a biomarker to predict axitinib resistance. Regarding the resistant mechanism, vascular endothelial cells with decreased INSR in RCC may secrete interferon-β and induce PD-L1.


Efficacy of fresh-frozen cadaveric surgical training for arteriovenous fistula in vascular access.

CST for AVF creation is useful for surgical education because it enables learning of surgical techniques that are almost equivalent to those in living bodies. In addition, this study suggested that CST not only contributes to the improvement of surgical skills of young surgeons but also promotes the reduction of anxiety and stress about AVF creation.

Twelve CST sessions were performed on nine FFCs. All training sessions allowed completion of AVF creation with a median operative time of 78.5 min. Although veins and arteries were more difficult to identify than in a living body, other surgical operations could be performed in the same way as in a living body. All the respondents stated that it was good for them to experience CST. In addition, 86% of surgeons responded that CST improved their surgical techniques, and 71% of surgeons responded that they were less anxious about AVF creation.


Assistent guide: A novel device for ureteral stent placement in robot-assisted intracorporeal ileal conduit.

We showed the safety and efficacy of the Assistent guide for ureteral stent placement in RICIC.

The International Journal of Medical Robotics + Computer Assisted Surgery : MRCAS


The impact of nutritional status and changes of body composition on the prognosis of metastatic renal cell carcinoma patients.

Nutritional status of mRCC patients may predict changes in body composition and be associated with their prognosis. J. Med. Invest. 70 : 80-87, February, 2023.

The Journal of Medical Investigation : JMI


Prostate-specific Antigen Levels Following Brachytherapy Impact Late Biochemical Recurrence in Japanese Patients With Localized Prostate Cancer.

PSA levels at 5 years post-treatment were associated with long-term recurrence of localized prostate cancer, which can help alleviate patient anxiety concerning prostate cancer recurrence if PSA levels remain low at 5 years after LDR-BT.


未固定凍結遺体を用いた心停止下献腎摘出教育の試み

未固定凍結遺体を用いた心停止下献腎摘出教育の試み


Comparison of robot-assisted partial nephrectomy with soft coagulation and double-layer technique for complex and non-complex tumors.

Single-layer suturing with soft coagulation achieves renal function and perioperative outcomes comparable to those of double-layer suturing regardless of complexity.


A propensity score matching study on robot-assisted radical cystectomy for older patients: comparison of intracorporeal ileal conduit and cutaneous ureterostomy.

In older patients, the ICIC group showed non-inferior surgical and oncological outcomes compared with the CUS group. Urinary diversion following RARC in older patients should be carefully selected by considering not only the age but also the general condition (including comorbidities) of the patient.

The median age was lower in the ICIC group compared with the CUS group, and the proportion of high-risk cases (ECOG-PS ≥ 2 or ASA-PS ≥ 3) did not differ. The median operation time was longer in the ICIC group, and estimated blood loss was higher, compared with the CUS group. There were no significant differences in the incidence of complications within the first 30 postoperative days, incidence of complications 30-90 days after surgery, 2-year overall survival, 2-year cancer-specific survival, and 2-year recurrence-free survival. The stent-free rate was significantly lower in the CUS group than that in the ICIC group.


Recurrent multiple liver metastases of clear cell renal cell carcinoma with a significant response to sunitinib after nivolumab treatment.

Sunitinib after an IO-drug showed a significant effect in spite of only slight efficacy with other VEGFR-TKIs, which may have occurred through the alteration of the immunological microenvironment.

The patient was a 65-year-old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months.


A case of laparoscopic adhesiotomy for urodynia caused by bladder wall adhesion to the anterior abdominal wall after vesicoscopic ureteral reimplantation for vesicoureteral reflux.

We herein report an extremely rare case of urodynia caused by bladder wall adhesion to the anterior abdominal wall after vesicoscopic ureteral reimplantation for vesicoureteral reflux with resolution of the urodynia by laparoscopic adhesiotomy. A 13-year-old girl who had undergone vesicoscopic cross-trigonal ureteral reimplantation for bilateral grade IV vesicoureteral reflux subsequently experienced severe urodynia for 5 years until her self-report to the attending physician. Magnetic resonance imaging suggested that bladder wall adhesion to the anterior abdominal wall may have caused the urodynia. Therefore, laparoscopic adhesiotomy of the bladder was performed. Notably, her urodynia disappeared immediately after surgery.


Leptomeningeal carcinomatosis in small cell carcinoma of the prostate.

Careful monitoring of the central nervous system should be considered in small cell carcinoma of the prostate patients.

A 69-year-old man visited our hospital due to dysuria and edema. Bilateral hydronephrosis and lymph node metastases due to a pelvic tumor were observed. Although the prostate-specific antigen level was normal, the tumor was suspected to originate from the prostate. He underwent percutaneous nephrostomy and prostate biopsy. Histopathology revealed small cell carcinoma accompanied by increased pro-gastrin-releasing peptide and neuron-specific enolase levels. After receiving systemic chemotherapy with carboplatin and etoposide and radiation therapy for prostate, these lesions gradually decreased in size, and tumor markers normalized. Ten months after the initial diagnosis, he developed consciousness disorder and seizure. Magnetic resonance imaging revealed leptomeningeal carcinomatosis without any other recurrences and elevated tumor markers. He died 4 weeks after these symptoms appeared.


Appropriate management reduces radiation exposure in daily urological practice

To identify and raise awareness of the radiation exposure of urologists due to X-ray fluoroscopic procedures in daily practice. This was a single-center, cohort study of 30 consecutive patients who underwent periodic percutaneous or transurethral replacements of urinary tract catheters. A total of 55 replacements every 3 months with cases aligned were performed by a single urologist. The urologist's radiation exposure and the incident dose to patients per case were measured with thermoluminescent dosimeters. In the latter 3-month period, the pulse fluoroscopy condition was changed from 15 to 7.5 pulses per second, and collimation was added to the field of view. In the analysis of all patients, the use of a modified pulse rate and collimation did not affect the fluoroscopy time, but it did significantly reduce the air kerma and dose area product; in addition, with respect to the medical exposure dose during percutaneous catheter replacement, fluoroscopy time was longer, but air kerma and dose area product showed significant decreases. As with decreases in medical exposure of patients, the equivalent dose for eye lenses of the urologist decreased from 1.2 mSv in the first 3-month period to 0.2 mSv in the second 3-month period. Similarly, the exposure dose for the extremities also decreased significantly, from 33.9 mSv to 8.1 mSv. Urologists are exposed to non-negligible amounts of radiation due to fluoroscopy. Appropriate management such as modified pulse fluoroscopy condition and precautions are required.


High-Grade Renal Mucinous Tubular and Spindle Cell Carcinoma

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma. Although usually indolent, high-grade MTSCC has been reported to exhibit an aggressive clinical course. Herein, we report a case of high-grade renal MTSCC. An 86-year-old man visited our hospital with fever and fatigue. Based on contrast-enhanced computed tomography findings, the patient was diagnosed with clinical stage T2aN0M0 right renal cell carcinoma and underwent laparoscopic radical nephrectomy. Histological examination showed tubular to tubulopapillary structures accompanied by mucinous stroma, suggesting high-grade renal MTSCC. He remained recurrence- and metastasis-free 6 months after nephrectomy. Since high-grade renal MTSCC may have an aggressive clinical course, such patients should be observed carefully after radical nephrectomy.


A Case of Pappilary Renal Cell Caircinoma which Responded Well to the Combination Therapy of Ipilimumab and Nivolumab --A CASE REPORT--

イピリムマブ・ニボルマブ併用療法が著効した乳頭状腎細胞癌の1例

We report a case of papillary renal cell carcinoma that responded well to the combination of ipilimumab and nivolumab. The patient was a 68-year-old male who was being followed up for a small left renal mass without treatment. Two years later, computed tomography (CT) showed enlarged cervical and para-aortic lymph nodes, and lymph node biopsy suggested metastases of the cancer. After resection of the renal tumor, we performed pararenal aortic lymph node biopsy, and we diagnosed the case as papillary renal cell carcinoma type 1 with lymph node metastasis. The combination of ipilimumab and nivolumab each metastatic site showed regression on CT. Since immune-related adverse events occurred during the therapy nivolumab was discontinued, but partial response of the metastases was maintained.


Micropapillary Variant of Urothelial Carcinoma in a Hemodialysis Patient

The micropapillary variant of urothelial carcinoma (MPUC) is an aggressive form of urothelial carcinoma with high metastatic potential and a poor prognosis. Although various therapies have been reported, there is still no established treatment strategy for MPUC due to its rarity. The incidence of urinary tract malignancies is higher in patients undergoing hemodialysis (HD) than in healthy individuals. Here, we report the case of an 82-year-old man on HD with end-stage kidney disease who visited our hospital for macrohematuria. Cystoscopy followed by computed tomography and urine cytology revealed a sessile papillary tumor around the left bladder wall. We performed transurethral resection of the bladder tumor. Based on histopathological and imaging findings indicative of clinical-stage T3N0M0 MPUC, we performed radical cystectomy. Histopathology revealed a pathological stage T4aN0M0 MPUC. Two months after the cystectomy, the patient complained of constipation and painful defecation due to local recurrence and rectal invasion. While colostomy was performed to improve defecation 3 months after cystectomy, he did not receive any chemotherapy due to his progressively worsening general condition. Six months after cystectomy, he died following rapid metastases. Our findings, in this case, confirm that bladder cancer in HD patients tends to be pathologically more advanced. Therefore, regular screening is recommended for its early detection in HD patients.


The patient-side surgeon plays a key role in facilitating robot-assisted intracorporeal ileal conduit urinary diversion in men

The influence of the console surgeon on the feasibility and outcome of various robot-assisted surgeries has been evaluated. These variables may be partially affected by the skills of the patient-side surgeon (PSS), but this has not been evaluated using objective data. This study aimed to describe the surgical techniques of the PSS in robot-assisted radical cystectomy (RARC) and intracorporeal ileal conduit (ICIC) urinary diversion and objectively examine the changes in surgical outcomes with increasing PSS experience. During a 3-year period, 28 men underwent RARC and ICIC urinary diversion. Clinical characteristics and surgical outcomes were compared between patients who underwent surgery early (first half group) or late in the study period (second half group). The pre-docking incision enabled easy specimen removal. The glove port technique widened the working space of the PSS. The stay suture allowed the PSS to control the distal portion of the conduit, facilitating the passage of the ureteral stents. During stoma creation, pneumoperitoneum pressure was lost by opening the abdominal cavity. To overcome this problem, the robotic arm was used to lift the abdominal wall to maintain the surgical field and facilitate the PSS procedure. Compared with the first half group, the second half group had significantly shorter times for urinary diversion (202 min vs 148 min, p < 0.001), ileal isolation and anastomosis (73 min vs 45 min, p < 0.001), and stenting (23.0 min vs 6.5 min, p < 0.001). As the experience of the PSS increased, the time of the PSS procedures decreased.


Poor Outcome due to the Plasmacytoid Variant of Urothelial Carcinoma

A 72-year-old man visited our hospital due to pollakiuria and lower abdominal pain. Urinary cytology was positive, and cystoscopy revealed diffuse edematous nonpapillary tumor. We performed transurethral biopsy, and clinical stage T3 plasmacytoid variant of urothelial carcinoma (PUC) was diagnosed. Although we planned for radical cystectomy, peritoneal dissemination and lung and pelvic lymph node metastases appeared 3 weeks after the initial visit. We also planned for chemotherapy; however, the metastases rapidly progressed, and he died 7 weeks after the biopsy. PUC is rare and shows an aggressive clinical course and poor prognosis.


Clinical application of virtual imaging guided Robot-assisted partial nephrectomy.

Objectives : To evaluate whether virtual partial nephrectomy images could help surgeons identify vascular and collecting system around tumors during actual surgery. Materials & methods : We retrospectively analyzed 36 patients who underwent robot-assisted partial nephrectomy (RAPN) between 2016 and 2017. Virtual partial nephrectomy images were created from preoperative CT images using computer software, and then analyzed. For analysis, blood vessels and collecting system portions within a 5-mm-thick safety margin around the tumor were examined. During analysis, we predicted whether targeted vasculature around the tumor would require clipping or suturing during surgery, and also whether the collecting system would require opening during resection. Surgical outcomes for virtual partial nephrectomy analyses and actual RAPNs were compared and analyzed for sensitivity and specificity. Results : In 36 cases, 119 arteries and 100 veins were targeted on virtual partial nephrectomy images. Arterial suturing or clipping for hemostasis showed a sensitivity and specificity of 83.3% and 84.5%, respectively. For veins, the sensitivity and specificity were 39.1% and 92.2%, respectively. Collecting system opening prediction sensitivity was 85.7%, and specificity was 65.2%. Conclusion : Virtual partial nephrectomy imaging is useful for RAPN planning, particularly regarding arteries and the collecting system. It is hoped that techniques for visualizing veins will improve. J. Med. Invest. 69 : 237-243, August, 2022.

The Journal of Medical Investigation : JMI


腎移植後のリンパ漏にリンパ管造影が効果的であった3例

腎移植後のリンパ漏にリンパ管造影が効果的であった3例


Two Cases of Robot-Assisted Total Pelvic Exenteration and Intracorporeal Ileal Conduit for Locally Advanced Rectal Cancer

局所進行直腸癌に対してロボット支援骨盤内臓全摘除術および体腔内回腸導管造設術を施行した2例


A Case of Robot-Assisted Radical Cystoprostatectomy for Locally Advanced Prostate Cancer with Bladder Infiltration

膀胱浸潤を来たした局所進行性前立腺癌に対してロボット支援腹腔鏡下膀胱前立腺全摘除術を施行した1例

While robot-assisted radical cystoprostatectomy (RARC) for locally advanced prostate cancer (LAPC) may sometimes prove to be excessive treatment, it can significantly reduce the risk of positive surgical margins and lower urinary tract obstruction in some cases. Here, we report a case of LAPC treated with RARC in a patient with right hydronephrosis due to bladder infiltration and left hypoplastic kidney. A 71-year-old man presented with frequent urination in August 2019. Prostate-specific antigen (PSA) level was 8.633 ng/ml, and magnetic resonance imaging led to the suspicion that the prostate cancer extended beyond the prostate capsule without distant metastasis. Prostatic biopsy revealed Gleason score 10 (5+5) adenocarcinoma in 8 out of 8 specimens. We diagnosed left hypoplastic kidney and LAPC with right hydronephrosis due to bladder infiltration. We performed percutaneous right nephrostomy and started neoadjuvant hormone therapy. RARC and intracorporeal ileal conduit were performed in March 2020. The prostate was adherent to the anterior surface of the rectum and was difficult to remove. At present, five months after the surgery, the patient remains free of recurrence and metastasis with PSA level <0.003 ng/ml. RARC for LAPC with bladder infiltration can be an effective therapeutic strategy in some cases.


Efficacy of the direct grasping technique using pean forceps under fluoroscopy to replace ureteral stents in women

Purpose : To evaluate the efficacy of the direct grasping technique using pean forceps under fluoroscopic guidance for ureteral stent replacement in women. Methods : Between April 2018 and September 2020, 28 female patients underwent ureteral stent replacements at our facility, and 184 stent replacement procedures were performed. A total of 127 stents were replaced using pean forceps under fluoroscopic guidance (pean forceps group), and 57 stents were replaced using the cystoscope (cystoscopy group). Clinical characteristics and surgical outcomes were compared between the groups. Results : All stents were successfully replaced. There was a statistically significant difference in the procedure time between the two groups (median [interquartile range], pean forceps group : 10.8 [8.2-13.9] minutes vs. cystoscopy group : 15.8 [11.1-20.9] minutes, P < 0.001). There were no intraoperative complications in either group and no difference in the incidence of postoperative complications (pean forceps group : 1.6% vs. cystoscopy group : 1.8%, P = 1.000). Fluoroscopy time was longer in the pean forceps group, although this difference was not statistically significant (pean forceps group : 38.9 [22.6-60.1] seconds vs. cystoscopy group : 33.0 [20.0-48.9] seconds, P = 0.0558). Conclusion : The direct grasping technique using pean forceps under fluoroscopy may be a beneficial alternative to cystoscopy for ureteral stent replacement in women. J. Med. Invest. 68 : 326-329, August, 2021.


[A Case of Pelvic Organ Prolapse and Bladder Diverticulum Surgically Treated at the Same Time].

骨盤臓器脱と膀胱憩室を同時に治療した1例

We report a case of bladder diverticulum presumably caused by lower urinary tract dysfunction due to pelvic organ prolapse (POP) simultaneously treated with transurethral coagulation (TUC) of the bladder diverticulum and laparoscopic sacrocolpopexy (LSC). A literature search showed this is the first report of bladder diverticulum and POP surgically treated at the same time. A 71-year-old woman was referred to our hospital for the treatment of cystocele. She had both storage and voiding symptoms. She had a POPQ stage III cystocele and stage I uterine prolapse. Ultrasonography and computed tomographic scan showed a large volume of residual urine along with a bladder diverticulum. Since urodynamic studies revealed a low compliance bladder and obstruction, we opined that the lower urinary tract symptoms were induced by the cystocele. TUC of the bladder diverticulum and LSC were performed at the same time. After the operation, clean intermittent catheterization (CIC) was needed once a day for one month. Gradually, residual urine decreased and CIC became unnecessary. The bladder diverticulum disappeared, and there has been no recurrence of POP.


Low Expression of Toll-like Receptor 4 Is Associated With Poor Prognosis in Bladder Cancer.

Low TLR4 expression was correlated with tumor progression.


腎摘除術, 副腎摘除術における血管処理のポイント

腎摘除術, 副腎摘除術における血管処理のポイント

 腹腔鏡下腎摘除術や副腎摘除術は, 簡便な低侵襲手術として標準化され普及している. 本項では, 腎茎の血管処理を安全に遂行するための術前準備, 血管処理の基本について述べた. 術前に血管走行などの作図を行い, 手術手順を確認する準備が重要である. 術前に把握されていない構造物に遭遇した際には, 手技を中断し, 画像を見直すことで安全に手術を遂行できる. また, 手術後に手術動画を省みることで, 画像読影力や作図能力は向上していく.

 血管処理は, 「血管以外の組織を凝固切離した結果, 血管だけが残った」という考えで, 丁寧に基本に忠実に行う. 助手の術野展開と鏡の選定を行い, 処理に適した角度から良好な視野を得る. 血管は把持せず, 血管に垂直に鉗子を動かし剥離を行う. 微量な出血も放置せず, その都度止血し無血野を保つ. 各種デバイスの特性を理解し, 処理に最適なデバイスを選択する.


[Renal Angiomyolipoma Extending into the Renal Vein --A Case Report-].

腎静脈への進展を認めた腎血管筋脂肪腫の1例

We report a case of left renal angiomyolipoma extending into the renal vein. A 67-year-old woman showed a left renal tumor which was 6 cm in diameter and had density equal to fat tissue in computed tomography. We suspected liposarcoma and performed radical nephrectomy and resection of thrombus. The pathological diagnosis was angiomyolipoma with no malignancy. To our knowledge, renal angiomyolipoma with tumor thrombus has been reported in 62 cases, and pulmonary embolism developed in 9 of these cases. We conclude that surgical treatment is effective in treating angiomyolipoma with tumor thrombus.


【小児腹腔内精巣-どう扱うか?】腹腔内精巣に対する腹腔鏡下二期的Fowler-Stephens法


Predictive Factors for Prolonged Urination Disorder After Permanent 125I Brachytherapy for Localized Prostate Cancer

We assessed the change in LUTS after prostate brachytherapy to reveal factors for prolonged urination disorder. Four hundred and four patients received prostate brachytherapy at our institution and were followed-up for at least 2 years. We evaluated the correlation of mean IPSS changes and clinical factors. Using multivariate analysis, we also evaluated clinical factors with potential to delay IPSS resolution. In cases with prostate volume more than 30 cm, radiation dose to 90% of prostate volume (D90) more than 160 Gy, and radiation dose to 30% of the urethral volume (UD30) more than 240 Gy, mean IPSS levels were significantly higher, even 30 months after treatment. On multivariate analysis, baseline IPSS more than 8 points and D90 more than 160 Gy were significant predictors for delayed IPSS resolution. Our data suggest that higher baseline IPSS and higher D90 were predictors for prolonged urination disorder.


The Involvement of Hepatocyte Growth Factor-MET-Matrix Metalloproteinase 1 Signaling in Bladder Cancer Invasiveness and Proliferation. Effect of the MET Inhibitor, Cabozantinib (XL184), on Bladder Cancer Cells.

To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies. We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells. These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscle-invasive BCa.


LAPAROSCOPIC PYELOPLASTY IN CHILDREN-ADVANCEMENT OF NEW TECHNIQUES

小児泌尿器科イノベーション エンドウロロジーの進歩 小児に対する腹腔鏡下腎盂形成術の進歩


Clinical Significance of Neoadjuvant Combined Androgen Blockade for More Than Six Months in Patients with Localized Prostate Cancer Treated with Prostate Brachytherapy.

The aim of this study is to clarify the clinical significance of neoadjuvant combined androgen blockade (CAB) for ≥ 6 months in patients with localized prostate cancer. A total of 431 patients with localized prostate cancer who underwent prostate brachytherapy (BT) with or without neoadjuvant CAB for ≥ 6 months with mean follow-up time of 64.6 months (range 24-108 months) were evaluated retrospectively. Of those 431, 232 patients received BT in combination with neoadjuvant CAB for ≥ 6 months. Biochemical recurrence-free rates (BRFRs) in 364 patients with at least 3 years of follow-up were evaluated by log-rank test. BRFR in patients with low-, intermediate- and high-risk prostate cancer were 98.1, 94.2 and 89.1%, respectively. In patients with intermediate-risk prostate cancer only, neoadjuvant CAB was significantly associated with BRFR (p = 0.0468). Especially in patients with intermediate-risk prostate cancer with radiation dose received by 90% of the prostate (D90) < 180 Gy, neoadjuvant CAB exerted a favorable impact on BRFR (p = 0.0429). On multivariate analyses, neoadjuvant CAB and D90 were independent predictors of BRFR (p = 0.0061 and p < 0.0001, respectively). Neoadjuvant CAB for ≥ 6 months has a favorable impact on BRFR in patients with intermediate-risk prostate cancer, particularly in patients with relatively low radiation doses of D90.


RETROPERITONEAL SCHWANNOMA WITH INCREASED F18-FLUORODEOXYGLUCOSE UPTAKE ON POSITRON EMISSION TOMOGRAPHY : A CASE REPORT

FDG-PETにて高集積を認めた後腹膜神経鞘腫の1例


Long-Term Administration of Docetaxel Over 70 Cycles for Castration-Resistant Prostate Cancer.


Changes in levels of prostate-specific antigen and testosterone following discontinuation of long-term hormone therapy for non-metastatic prostate cancer.

We evaluated changes in levels of prostate-specific antigen (PSA) and testosterone following discontinuation of long-term hormone therapy for non-metastatic prostate cancer. Treatment was discontinued in 31 patients with non-metastatic prostate cancer (clinical stage B-C) after ≥ 5 years of hormone therapy, during which time PSA level had been maintained less than 0.5 ng/ml. PSA and testosterone levels were measured after discontinuation of therapy. PSA > 4.0 ng/ml was defined as PSA relapse in this study. Mean age at discontinuation of hormone therapy was 78.7 years (range, 66-90). Mean duration of follow-up after discontinuation of therapy was 25.5 months. PSA non-relapse rate was quite high (87.1%). 4 of the 31 patients showed PSA relapse, after 12-24 months. Testosterone level exceeded castration level (< 1.0 ng/ml) in 3 patients, each of whom developed PSA relapse. During follow-up, the PSA relapse rate was relatively low. These results suggest that treatment may be safely discontinued in many prostate cancer patients. In addition, rate of testosterone recovery after treatment discontinuation may be associated with PSA relapse. When considered the adaptation of discontinued, or intermittent hormone therapy for aged people, these findings may be useful.

The Journal of Medical Investigation : JMI


Updated systemic therapy for advanced/metastatic renal cell carcinoma and prostate cancer

腎癌・前立腺癌に対する最新の薬物療法

As advanced renal cell carcinoma (RCC) shows resistance to anti-cancer drugs, immunotherapy had been the mainstay of systemic therapy. Recently, molecular targeted agents including VEGF and mTOR inhibitors have been introduced, and so systemic therapy for advanced RCC has been significantly altered. VEGF inhibitors show marked efficacy in regard to tumor size reduction, and the representative adverse events include hypertension, hand-foot syndrome, and hypothyroidism. mTOR inhibitors have modest effects for tumor size reduction, and the specific adverse events include stomatitis, hyperglycemia, hyperlipidemia, and interstitial pneumonia. The introduction of molecular targeted agents has improved survival in advanced RCC patients. Hormonal therapy is at the center of systemic therapy for advanced prostate cancer patients. Castration or LH-RH analogues suppress the proliferation of prostate cancer cells by decreasing androgen production in the testes. Anti-androgens inhibit the binding of testosterone to androgen receptors, and combination therapy of castration or LH-RH analogues and anti-androgens, called maximum androgen blockade, shows enhanced efficacy for advanced prostate cancer. Docetaxel is administered for castration-resistant prostate cancer, and prolongs survival compared to previously used anti-cancer drugs. Regarding new drugs for prostate cancer, an LH-RH antagonist, a CYP17 inhibitor of androgen production in the adrenal glands, and new anti-androgens with a higher affinity for androgen receptors have been developed for clinical use.


Impacts of clinicopathologic and operative factors on short-term and long-term survival in renal cell carcinoma with venous tumor thrombus extension: a multi-institutional retrospective study in Japan.

Although the percentage of patients with renal cell carcinoma (RCC) extending into venous systems is unexpectedly high, the prognostic impact and independency of venous tumor thrombus-related factors on overall survival (OS) remain controversial. Furthermore, the prognostic impact of various clinicopathologic factors including tumor thrombus-related factors on OS may change with elapsed years after the intervention and also with follow-up duration of participants. The aim of the study is to explore independent and universal predictive preoperative and intraoperative clinicopathologic factors on OS in patients with RCC extending into venous systems using subgroup analysis in terms of restricted follow-up duration and yearly-based survivors. Between 1980 and 2009, 292 patients diagnosed with RCC with venous tumor thrombus were retrospectively registered for this study. The prognostic impacts of various clinicopathologic and surgical treatment factors including levels of venous thrombus, venous wall invasion status and likelihood of aggressive cytoreductive operation, were investigated using Kaplan-Meier method and following multivariate Cox proportional hazards model for all patients and those still alive at 1, 2, and 3 years of follow-up. To investigate the impact of follow-up duration on the statistical analyses, multivariate logistic regression analyses were used to explore prognostic factors using restricted data until 1, 2, and 3 years of follow-up. The median follow-up duration was 40.4 months. The 5-year OS was 47.6%. Several independent predictive factors were identified in each subgroup analysis in terms of yearly-based survival and restricted follow-up duration. The presence of tumor thrombus invading to venous wall was independently related to OS in the full-range follow-up data and in survivors at 2 and 3 years of follow-up. Using restricted follow-up data until 1, 2, and 3 years of follow-up, many independent predictive factors changed with follow-up duration, but surgical category could be universal and independent predictive factors. The most universal factors affecting improvement both in short-term and long-term survivals could be cytoreductive surgery and absence of venous wall invasion. It may mean that feasible aggressive cytoreductive operation following more reliable preoperative imaging for predicting venous wall invasion status would improve OS for patients with RCC extending into venous systems.


NON-MUSCLE INVASIVE BLADDER CANCER WITH MULTIPLE BONE METASTASIS WITHOUT LOCAL INVASION : A CASE REPORT

多発骨転移をきたした筋層非浸潤性膀胱癌の1例

A 66-year-old man with superficial bladder cancer was treated with transurethral resection (TURBT) in October 2011. The pathological diagnosis was urothelial carcinoma (UC), grade 2, T1. A second TURBT was performed one month later. The pathological diagnosis was UC, grade 3, T1. He was treated with intravesical bacillus Calmette-Guerin (BCG) after TURBT. His progress was satisfactory, but a small superficial bladder cancer was found on cystoscopy in August 2012. He was going to be treated with TURBT, but the serum alkaline phosphatase level was abnormally high on preoperative evaluation. Bone scintigraphy showed multiple bone metastases from non-muscle invasive bladder cancer (NMIBC) without local invasion. He was started on combined chemotherapy with 1,000 mg/m2 gemcitabine on days 1, 8 and 15 and 70 mg/m2 cisplatin on day 2 every four weeks. He received denosumab for multiple bone metastases at the same time. Although he subsequently developed severe hypocalcemia, treatment was continued, and he completed four courses of chemotherapy. Bone scintigraphy and contrast-enhanced computed tomography showed reduction of the multiple bone metastases, and alkaline phosphatase decreased to the normal range. It is rare for NMIBC without local invasion to metastasize to other organs. Thus, it is necessary to consider distant metastases in patients with NMIBC.


Prognostic factors of patients with metastatic renal cell carcinoma with removed metastases: a multicenter study of 556 patients.

To investigate the prognosis and prognostic factors of patients with metastatic renal cell carcinoma who underwent metastasectomy. We sent questionnaires to Japanese hospitals. The questionnaires included data of patients with metastatic renal cell carcinoma who had their metastatic lesions removed between January 1988 and December 2009. We collected them and retrospectively analyzed these data and calculated the overall survival from the first metastasectomy until death or last follow-up. We also analyzed the relationship between survival and clinico-pathologic features and determined adverse prognostic factors. Furthermore, we identified a poor prognostic group by counting the number of prognostic factors. A sample size of 556 patients from 48 institutions was studied. The median overall survival was 80 months. Four adverse prognostic factors were detected: incomplete resection by metastasectomy (hazard ratio [HR], 2.15), brain metastasis (HR, 3.73), >1.0 mg/dL C-reactive protein (HR, 2.45), and the highest histologic grade in Japanese classification (nuclei of tumor cells are larger than nuclei of normal tubular cells; HR, 1.88). The median overall survivals of patients with 3 or 4 prognostic factors, 2 factors, and 0 and 1 factors were 10 months, 42 months, and 105 months, respectively. Four adverse prognostic factors for predicting the survival of patients with removed metastases were identified. Patients with 3 or 4 of these adverse prognostic factors had a worse prognosis.


小児低形成腎/機能低下腎に対する腹腔鏡下腎摘除術の臨床的検討

小児低形成腎/機能低下腎に対する腹腔鏡下腎摘除術の臨床的検討

We reviewed the results of laparoscopic nephrectomy for children with a hypoplastic or poorly functioning kidney in our department. Laparoscopic nephrectomy was performed in 10 patients including 1 boy and 9 girls. The patients' median age was 5.5 years old. There were 8 patients with a hypoplastic kidney and an ectopic ureter, and 2 patients with a poorly functioning kidney and a megaureter or vesicoureteral reflux. Laparoscopic nephrectomy was conducted transperitoneally in 5 and retroperitoneally in 5 patients. The median operative time was 167 minutes. There was no intraoperative complication. Postoperatively, subcutaneous emphysema and fever developed in one patient each. 7 patients used an analgesic suppository once or several times, and 3 patients received no analgesics. Oral intake was started at a median of 1 day postoperatively. The median hospital stay after surgery was 4.5 days. Laparoscopic nephrectomy for a hypoplastic and poorly functioning kidney in children is a minimally invasive surgery.

当科において小児の低形成腎/機能低下腎に対する鏡視下腎摘除術を再検討した．1993年12月より，低形成腎/機能低下腎の小児10例に対し，鏡視下腎摘除術を施行した．年齢の中央値5.5歳，男1例，女9例．尿管異所開口に伴う低形成腎8例，巨大尿管症，高度VURによる機能低下腎が各1例．手術は，経腹膜的アプローチ5例，後腹膜的アプローチ5例，手術時間中央値は167分．術中合併症はなく，術後合併症は，皮下気腫1例，発熱1例．術後鎮痛剤は，3例は使用なし，7例は術後に坐薬を1∼数回使用．食事開始は中央値で術後1日目，歩行開始日中央値は術後1.5日．術後入院期間中央値は4.5日，術後から退院可能日までの中央値3.0日．小児の低形成腎/機能低下腎に対する鏡視下腎摘除術は，術後の疼痛も少なく，美容的にも良好で，標準的な低侵襲手術である．


Substitution of antiandrogens and tegafur-uracil combination therapy for castration-resistant prostate cancer: results of a multi-center randomized phase II study

We conducted this study to determine whether substitution with anti-androgen (SOA) and tegafur-uracil (a pro-drug of 5-FU) combination therapy is more effective than SOA alone after relapse from initial hormonal therapy. Patients who were histologically confirmed and relapsed after initial hormonal therapy were included. All patients were randomly allocated into two groups: SOA alone (group A) or SOA combined with tegafur-uracil (group B). The mRNA expression of four enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phospho-ribosyltransferase (OPRT) and thymidine phosphorylase (TP), in prostate cancer cells was analyzed by quantitative reverse-transcription polymerase chain reaction. Fifty-two patients were enrolled in this study. The median age was 77 (range: 47-92) years. The PSA response rate in group B (61.5%) tended to be higher compared to that in group A (34.6%) (p=0.095). Group B (median: 15.9 months) had a significantly longer time to PSA progression (TTP) compared to group A (6.4 months) (p=0.014). In patients with a lower TS expression or a higher OPRT expression, group B demonstrated a higher PSA response rate compared to group A (p=0.019 and p=0.041, respectively). In addition, in the patients with a lower TS expression, group B demonstrated a significantly longer TTP compared to group A (p=0.018). There were no severe adverse events in either treatment group. After relapse from initial hormonal therapy, SOA combined with tegafur-uracil is effective and well tolerated. The TS mRNA expression level may be a predictive factor for this combination therapy.


CLINICAL EXPERIENCE OF INTERSTITIAL CYSTITIS TREATED WITH HYDRODISTENSION

間質性膀胱炎に対する水圧拡張術の経験


TREATMENT ALGORITHM FOR ADVANCED/METASTATIC RENAL CELL CARCINOMA : AVAILABILITY OF NEW CANDIDATE AGENTS FOR USE IN THE NEAR FUTURE

腎細胞癌の薬物療法:治療アルゴリズムの近未来予測


Mineralocorticoid receptor expression in human penile corpus cavernosum

Mineralocorticoid receptor (MR) is known to play physiological and pathophysiological roles in the cardiovascular system, and MR activation directly damages these organs. The aim of this study was to evaluate the expression of MR and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in the human penile corpus cavernosum. MR and 11β-HSD2 expression was assayed in human penile tissues, and also in human renal tissues as a positive control. Expressions of MR mRNA and 11β-HSD2 mRNA were evaluated using reverse transcription polymerase chain reaction (RT-PCR). MR and 11β-HSD2 were visually identified using immunofluorescence analysis. MR mRNA expression in human penis was confirmed by RT-PCR. On quantitative RT-PCR analysis, 11β-HSD2 mRNA expression was detected at minimal levels in penile tissue. Immunofluorescence analysis revealed positive staining for MR and negative staining for 11β-HSD2 in smooth muscle cells of the corpus cavernosum. This study demonstrated the presence of MR and the absence of 11β-HSD2 in human penile corpus cavernosum. Considering that MR activation causes various organ damages, MR blockade in human penile corpus cavernosum may have therapeutic benefits. Investigations for the penile effects of MR activation have the potential to provide new treatment approaches for erectile dysfunction.


CLINICAL EXPERIENCE OF REITER'S SYNDROME FOLLOWING BCG INTRAVESICAL THERAPY

BCG膀胱内注入療法に合併したReiter症候群の経験


分子標的薬投与中に腸管穿孔をきたした2例

分子標的薬投与中に腸管穿孔をきたした2例


BCG膀胱内注入療法後に発症した結核性精巣上体炎の1例

BCG膀胱内注入療法後に発症した結核性精巣上体炎の1例


A new prognostic classification for overall survival in Asian patients with previously untreated metastatic renal cell carcinoma

The aims of the present study were to: (i) develop a clinically useful prognostic classification in Asian patients with metastatic renal cell carcinoma (RCC) by combining metastatic features with several pretreatment parameters; and (ii) evaluate the validity of this prognostic classification. Baseline characteristics and outcomes were collected for 361 patients who underwent interferon-α-based therapy between 1995 and 2005. Relationships between overall survival (OS) and potential prognostic factors were assessed using Cox's proportional hazard model. The predictive performance of the model was evaluated using bootstrap resampling procedures and by using an independent dataset obtained from randomly selected institutions. The predictive accuracy was measured using the concordance index (c-index). Four factors were identified as independent prognostic factors: time from initial diagnosis to treatment, anemia, elevated lactate dehydrogenase (LDH), and poor prognostic metastatic group (liver only, bone only, or multiple organ metastases). Each patient was assigned to one of three risk groups: favorable risk (none or one factor; n = 120), in which median OS was 51 months; intermediate risk (two factors; n = 101), in which median OS was 21 months; and poor risk (three or four factors; n = 102), in which median OS was 10 months. The c-index was 0.72 in the original dataset and 0.72 in 500 random bootstrap samples. In the independent dataset for external validation, the c-index was 0.73. Thus, the new prognostic classification is easily applicable for Asian patients with previously untreated metastatic RCC and should be incorporated into patient care, as well as clinical trials performed in Asia.


SEQUENTIAL THERAPY WITH MOLECULAR TARGETED AGENTS FOR ADVANCED RENAL CELL CARCINOMA

進行性腎細胞癌に対する薬物療法 いつ，何を，どう使う? 進行性腎癌に対する分子標的薬のsequential therapy


Up-regulation of Plakophilin-2 and Down-regulation of Plakophilin-3 are Correlated With Invasiveness in Bladder Cancer

To examine plakophilin proteins (Pkp) and 3 expression levels in bladder cancer, in particular their levels during cellular growth and invasion. Pkp is associated with the binding of cadherin to intermediate filaments of the cytoskeleton. The relative mRNA and protein expression levels of Pkp2 and 3 in bladder cancer cell lines were determined using quantitative real-time polymerase chain reaction and Western blot analyses. The cellular localization of Pkp2 and 3 proteins in bladder cancer cells was also assayed using immunohistochemistry. The proliferation and invasive activities of bladder cancer cells were evaluated using cell growth and in vitro cell invasion assays, and were compared with those of bladder cancer cells treated with Pkp2 and 3 small interfering RNAs. Pkp2 mRNA and protein levels were elevated, and those of Pkp3 were reduced, in bladder cancer cells that are known to exhibit increased proliferation and invasive activity. Pkp2/3 protein expression was predominantly observed in the cytoplasm of invasive bladder cancer cells and tissues. Pkp2 knockdown inhibited, and Pkp3 knockdown enhanced, invasion of bladder cancer cells, but these knockdowns did not alter cell proliferation. We conclude that high Pkp2, and low Pkp3, expression is associated with bladder cancer cell invasion and that neither Pkp2 nor Pkp3 is associated with cell proliferation. We further hypothesize that accumulation of Pkp2 and 3 in the cell cytoplasm, rather than their recruitment to the cell membrane, is related to an increased ability of the tumor to invade and metastasize.


Up-regulation of insulin-like growth factor-binding protein 3 by 5-fluorouracil (5-FU) leads to the potent anti-proliferative effect of androgen deprivation therapy combined with 5-FU in human prostate cancer cell lines.

In this study, we investigated the synergistic mechanism of anti-androgen and 5-fluorouracil (5-FU) combination therapy against castration-resistant prostate cancer (CRPC). Four prostate cancer cell lines, LNCaP, 22Rv1, DU145 and PC3, were examined for their growth dependency on androgens and the insulin-like growth factor 1 (IGF1). We assessed the expression changes of certain growth factor receptors and regulating proteins when treated with 5-FU, and found that 5-FU increased the expression of the IGF-binding protein 3 (IGFBP3). Furthermore, 5-FU inhibited the phosphorylation of Akt and p70 S6K, while the knockdown of IGFBP3 reduced the levels of poly (ADP-ribose) polymerase cleaved by 5-FU in PC3 cells. Therefore, the up-regulation of IGFBP3 by 5-FU not only inhibits cell growth by reducing the IGF1 signal but also induces apoptosis in PC3 cells. The synergistic effect of bicalutamide and 5-FU on 22Rv1 cells was reduced by IGFBP3 gene silencing using small-interfering RNA. These results suggest that the up-regulation of IGFBP3 induced by 5-FU plays an important role in the potent anti-tumor effect of 5-FU combined with anti-androgens on CRPC. Androgen-deprivation therapy combined with 5-FU could therefore be an appropriate therapy for CRPC patients.


中間リスク群，高リスク群前立腺癌に対するI-125密封小線源療法の治療成績

中間リスク群，高リスク群前立腺癌に対するI-125密封小線源療法の治療成績


Hydroxyflutamide enhances cellular sensitivity to 5-fluorouracil by suppressing thymidylate synthase expression in bicalutamide-resistant human prostate cancer cells

We investigated the antitumor effects of combination therapy with anti-androgens and 5-fluorouracil (5-FU), and examined the underlying mechanism of the treatment. Initially, we established the bicalutamide-resistant subline CDX25R from the androgen receptor (AR)-positive human prostate cancer cell line LNCaP through continuous exposure to bicalutamide. CDX25R cells lost the ability to respond to androgens, but still expressed AR. They showed significant resistance to bicalutamide, but had high sensitivity to hydroxyflutamide (OH-flutamide) compared with LNCaP cells. The CDX25R subline was thus considered to be a suitable model for prostate cancer that has developed resistance to first-line hormonal therapy but shows sensitivity to an alternative approach. Combined treatment with 5-FU and OH-flutamide had a synergistic effect on CDX25R cells. OH-flutamide decreased expression of the transcription factor E2F1, and subsequently of thymidylate synthase (TS), in CDX25R cells but not in AR-negative DU145 cells. This suggested that OH-flutamide enhanced the growth-inhibitory activity of 5-FU in CDX25R cells by reducing TS expression through the AR pathway. Combined therapy with 5-FU and OH-flutamide may, therefore, be appropriate for patients with prostate cancer that has acquired resistance to initial hormone therapy including bicalutamide.


The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma

To elucidate the incidence and mechanisms of sunitinib-induced thyroid atrophy, we investigated serial volumetric and functional changes, and evaluated histological changes of the thyroid gland in metastatic renal cell carcinoma patients who received sunitinib. Thyroid volume (by computed tomography volumetry) and thyroid function were measured at baseline, during the treatment, and at post-treatment periods. Histological evaluation of the thyroid gland was performed in four autopsied patients. The median reduction rate in thyroid volume at last evaluation during sunitinib treatment was 30% in all 17 patients. The incidence of hypothyroidism during sunitinib treatment was significantly higher in the high reduction rate group (n=8; more than 50% reduction in volume) than in the low reduction rate group (n=9; less than 50% reduction in volume). Half of the patients in the high reduction rate group exhibited a transient thyroid-stimulating hormone suppression, suggesting thyrotoxicosis during sunitinib treatment. Histological evaluation demonstrated atrophy of thyroid follicles and degeneration of follicular epithelial cells without critical diminution of vascular volume in the thyroid gland. Thyroid atrophy is frequently observed following sunitinib treatment and may be brought about by sunitinib-induced thyrotoxicosis or the direct effects of sunitinib that lead to degeneration of thyroid follicular cells.


CLINICAL REVIEW OF ELDERLY PATIENTS WITH RENAL TUMORS IN OUR HOSPITAL

超高齢者の泌尿器がん治療 当科における初診時80歳以上の腎腫瘍患者の臨床的検討

初診時80歳以上の腎腫瘍患者24例(男17例・女7例・中央値81.5歳)の成績を報告した．ECOG performance status(PS)は0:9例，1:7例，2:3例，3:1例，4:3例，不明:1例，臨床病期はstage I:11例，II:2例，III:5例，IV:6例であった．腎摘出術を施行したのは6例で，PSは0:4例，1:1例，2:1例，病期はstage I:4例，II:1例，III:1例であった．非手術の理由は，本人・家族が希望しない，手術適応外，合併症の存在などであった．全生存期間の中央値は25ヵ月で，stage I:44ヵ月，II:10ヵ月，III:9ヵ月，IV:25ヵ月であった．癌特異生存期間の中央値はstage I:44ヵ月，II:10ヵ月，III:15ヵ月，IV:18ヵ月であった．stage I・IIの13例を手術施行5例と非手術8例に分け比較したが，全生存率，癌特異生存率ともに有意差はなかった．また，stage III・IVを治療介入7例と無治療3例に分けて行った比較でも，同様に有意差はなかった．


cDNA microarray analysis assists in diagnosis of malignant intrarenal pheochromocytoma originally masquerading as a renal cell carcinoma

Intrarenal pheochromocytoma (paraganglioma) is a very rare tumour. Its diagnosis is often difficult to establish because of its rarity and its histological similarity to renal cell carcinoma (RCC). Recently, we examined the molecular signatures of different subtypes of kidney tumours by using cDNA microarray. The signature pattern for one tumour, which was originally diagnosed as granular cell RCC, was clearly distinct from that of any other subtype of kidney tumour, and led us to re-evaluate the case. Haematoxylin and eosin staining revealed histological features suggestive of pheochromocytoma, and immunohistochemical studies showed positive staining for neuroendocrine markers but not for keratin. A germline missense mutation, D119E, in the familial paraganglioma related gene succinate dehydrogenase subunit D (SDHD), was subsequently identified. The treatment modality was revised and radiotherapy was given, to which the patient responded, leading to a reduction in tumour size of 25% within the first month. To our knowledge, this is the first report of an intrarenal pheochromocytoma that was diagnosed with the assistance of cDNA microarray analysis.


A Molecular Classification of Papillary Renal Cell Carcinoma

Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analyses. Comparative genomic microarray analysis was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples with 15 independent tumors. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic subtypes: type 1, low-grade type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G1-S and G2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in class 1 tumors and of topoisomerase IIalpha in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting.


Altered expression of members of the IGF-axis in clear cell renal cell carcinoma

Renal cell carcinoma (RCC) is a heterogeneous disease and its biology is poorly understood. The commonest subtype identified is clear cell RCC. The insulin-like growth factor axis is intimately involved with many cellular roles including that of renal development. Dysregulation of this axis has frequently been demonstrated in cancer. In this study, we examine the expression of several IGF-axis components, including receptors, ligands, and binding proteins in clear cell renal cell carcinoma. A series of clear cell RCCs with matched normal kidney from the same individuals were obtained. Total RNA was extracted and expression levels of genes examined using RNase protection analysis. We confirm the dysregulation of the IGF-axis within clear cell renal cell carcinoma including the upregulation of IGFBP-3, which is further validated by immunohistochemical staining on a tissue array containing 50 RCC: positive staining in 29/30 clear cell; 1/10 papillary and 0/10 chromophobe. In addition, we demonstrate that the expression of the A isoform of the insulin receptor is significantly upregulated, while that of IGFBP-5 are significantly downregulated in this tumour subtype.


Expression of galectin-3 is Associated With Resistance to Anticancer Drug-Induced Apoptosis in prostate Cancer


Expression of angiopoietin-1 and -2, and its clinical significance in human bladder cancer

To investigate the relationship between angiopoietin-1 and -2 expression and the clinicopathological variables and clinical outcome in patients with bladder cancer treated by surgical resection, as both have been recently identified as antagonistic angiogenic factors which regulate tumour growth. The expression of angiopoietin-1 and -2 were assessed by immunohistochemistry in tissue sections from 52 transitional cell carcinomas of the bladder (33 grade 1, 15 grade 2, four grade 3, including two associated with carcinoma in situ; 22 were stage Ta, 19 T1 and 11 T2 tumours). Normal bladder specimens were also resected during each operation as controls. The expression angiopoietins were related to the clinicopathological variables of the tumours. Positive immunostaining was detected in 18 samples (35%) for angiopoietin-1 and in 23 (44) for angiopoietin-2. There was no significant difference in survival according to tumour angiopoietin-1 status in the patients, but in contrast the overall survival of patients with angiopoietin-2-positive tumours was significantly lower than for those with angiopoietin-2-negative tumours (P < 0.05). Positive angiopoietin-2 expression was significantly correlated with histological grade (P = 0.026), histological stage (P = 0.009) and poor prognosis (P < 0.05). On multivariate analysis, positive angiopoietin-2 expression was an independent negative predictor for survival (P = 0.042). These results suggest that angiopoietin-2 overexpression is associated with tumour progression, thereby indicating a poor prognosis for some patients treated by surgical resection for bladder carcinoma.


Gene Expression of Parathyroid Tumors --- Molecular Subclassification and Identification of the Potential Malignant Phenotype

Parathyroid tumors are heterogeneous, and diagnosis is often difficult using histologic and clinical features. We have undertaken expression profiling of 53 hereditary and sporadic parathyroid tumors to better define the molecular genetics of parathyroid tumors. A class discovery approach identified three distinct groups: (1) predominantly hyperplasia cluster, (2) HRPT2/carcinoma cluster consisting of sporadic carcinomas and benign and malignant tumors from Hyperparathyroidism-Jaw Tumor Syndrome patients, and (3) adenoma cluster consisting mainly of primary adenoma and MEN 1 tumors. Gene sets able to distinguish between the groups were identified and may serve as diagnostic biomarkers. We demonstrated, by both gene and protein expression, that Histone 1 Family 2, amyloid beta precursor protein, and E-cadherin are useful markers for parathyroid carcinoma and suggest that the presence of a HRPT2 mutation, whether germ-line or somatic, strongly influences the expression pattern of these 3 genes. Cluster 2, characterized by HRPT2 mutations, was the most striking, suggesting that parathyroid tumors with somatic HRPT2 mutation or tumors developing on a background of germ-line HRPT2 mutation follow pathways distinct from those involved in mutant MEN 1-related parathyroid tumors. Furthermore, our findings likely preclude an adenoma to carcinoma progression model for parathyroid tumorigenesis outside of the presence of either a germ-line or somatic HRPT2 mutation. These findings provide insights into the molecular pathways involved in parathyroid tumorigenesis and will contribute to a better understanding, diagnosis, and treatment of parathyroid tumors.


Gene expression profiling of mesoblastic nephroma and Wilms tumors comparison and clinical implications

To better understand the molecular mechanisms in the tumorigenesis and progression of mesoblastic nephroma (MN), we studied its gene expression profiles. MN is the most common tumor of the neonatal kidney. It occurs in a younger age group than the Wilms tumor (WT). To date, very little is known about the etiology and pathogenesis of MN. Using microarrays containing 22,943 cDNA, we analyzed the expression profiles of MN and compared its expression profiles with those of several other types of kidney tumors, including WT. MN has a distinct molecular signature that clusters close to the WT, suggesting that both types of tumor share some similarity in gene expression and biology. When comparing the two profiles closely, we identified a number of genes that are commonly upregulated in both tumors, including insulin-like growth factor 2, thrombospondin 4, and mesenchyme homeo box 1. We also identified a set of genes that distinguish MN from WT, some of which may underlie the difference in their behaviors and can be used as diagnostic markers. Among this group of genes, topoisomerase II-alpha, highly expressed in WTs, is not overexpressed in MN. Immunohistochemical staining of topoisomerase II-alpha in additional cases of WTs and MNs confirmed this distinction further. The results of our study demonstrated that MN has a distinct gene expression profile and that some of the newly identified genes can be potentially used as novel diagnostic markers.


Robust Classification of Renal Cell Carcinoma Based on Gene Expression Data and Predicted Cytogenetic Profiles

Renal cell carcinoma (RCC) is a heterogeneous disease that includes several histologically distinct subtypes. The most common RCC subtypes are clear cell, papillary, and chromophobe, and recent gene expression profiling studies suggest that classification of RCC based on transcriptional signatures could be beneficial. Traditionally, however, patterns of chromosomal alterations have been used to assist in the molecular classification of RCC. The purpose of this study was to determine whether it was possible to develop a classification model for the three major RCC subtypes that utilizes gene expression profiles as the bases for both molecular genetic and cytogenetic classification. Gene expression profiles were first used to build an expression-based RCC classifier. The RCC gene expression profiles were then examined for the presence of regional gene expression biases. Regional expression biases are genetic intervals that contain a disproportionate number of genes that are coordinately up- or down-regulated. The presence of a regional gene expression bias often indicates the presence of a chromosomal abnormality. In this study, we demonstrate an expression-based classifier can distinguish between the three most common RCC subtypes in 99% of cases (n = 73). We also demonstrate that detection of regional expression biases accurately identifies cytogenetic features common to RCC. Additionally, the in silico-derived cytogenetic profiles could be used to classify 81% of cases. Taken together, these data demonstrate that it is possible to construct a robust classification model for RCC using both transcriptional and cytogenetic features derived from a gene expression profile.


Gene Expression Profiling of Early- and Late-Relapse Nonseminomatous Germ Cell Tumor and Primitive Neuroectodermal Tumor of the Testis

To better understand the molecular mechanisms that underlay the development and progression of nonseminomatous germ cell tumor of testis (NSGCTT) as well as malignant transformation of teratoma and primitive neuroectodermal tumor (PNET). We studied the gene expression profiles of 17 retroperitoneal NSGCTTs (10 yolk sac tumors, 3 embryonal carcinomas, 4 teratomas) and 2 PNETs obtained from patients with two clinical outcomes. Tissue samples were obtained from the Indiana University. One group of NSGCTT and PNET patients developed metastases within 2 years (early-relapse) of initial successful treatment, and the other group developed metastases after 2 years (late-relapse). Gene expression in these groups of patients was quantified using cDNA microarrays and real-time relative quantitative PCR. We demonstrate that the gene expression profiles of these tumors correlate with histological type. In addition, we identify type-specific genes that may serve as novel diagnostic markers. We also identify a gene set that can distinguish between early-relapse and late-relapse yolk sac tumors. The expression differences of these genes may underlie the differences in clinical outcome and drug response of these tumors. This is the first study that used gene expression profiling to examine the molecular characteristics of the NSGCTTs and drug response in early- and late-relapse tumors. These results suggest that two molecularly distinct forms of NSGCTTs exist and that the integration of expression profile data with clinical parameters could enhance the diagnosis and prognosis of NSGCTTs. More importantly, the identified genes provide insight into the molecular mechanisms of aggressive NSGCTTs and suggest intervention strategies.


The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas

By positional cloning, we identified two breakpoint-spanning genes in a familial clear cell renal cell carcinoma (CCRCC)-associated t(1;3)(q32.1;q13.3): LSAMP and NORE1 (RASSF1 homolog). Both genes are downregulated in 9 of 9 RCC cell lines. While the NORE1A promoter predominantly presents partial methylation in 6 of the cell lines and 17/53 (32%) primary tumors, the LSAMP promoter is completely methylated in 5 of 9 cell lines and in 14/53 (26%) sporadic and 4 familial CCRCCs. Expression of LSAMP and NORE1A proteins in CCRCC cell lines inhibited cell proliferation. These characteristics indicate that LSAMP and NORE1A may represent new candidate tumor suppressors for CCRCC.


Molecular subclassification of kidney tumors and the discovery of new diagnostic markers

We analysed the expression profiles of 70 kidney tumors of different histological subtypes to determine if these subgroups can be distinguished by their gene expression profiles, and to gain insights into the molecular mechanisms underlying each subtype. In all, 39 clear cell renal cell carcinomas (RCC), seven primary and one metastatic papillary RCC, six granular RCC from old classification, five chromophobe RCC, five sarcomatoid RCC, two oncocytomas, three transitional cell carcinomas (TCC) of the renal pelvis and five Wilms' tumors were compared with noncancerous kidney tissues using microarrays containing 19,968 cDNAs. Based on global gene clustering of 3560 selected cDNAs, we found distinct molecular signatures in clear cell, papillary, chromophobe RCC/oncocytoma, TCC and Wilms' subtypes. The close clustering in each of these subtypes points to different tumorigenic pathways as reflected by their histological characteristics. In the clear cell RCC clustering, two subgroups emerged that correlated with clinical outcomes, confirming the potential use of gene expression signatures as a predictor of survival. In the so-called granular cell RCC (terminology for a subtype that is no longer preferred), none of the six cases clusters together, supporting the current view that they do not represent a single entity. Blinded histological re-evaluation of four cases of 'granular RCC' led to their reassignment to other existing histological subtypes, each compatible with our molecular classification. Finally, we found gene sets specific to each subtype. In order to establish the use of some of these genes as novel subtype markers, we selected four genes and performed immunohistochemical analysis on 40 cases of primary kidney tumors. The results were consistent with the gene expression microarray data: glutathione S-transferase alpha was highly expressed in clear cell RCC, alpha methylacyl racemase in papillary RCC, carbonic anhydrase II in chromophobe RCC and K19 in TCC. In conclusion, we demonstrated that molecular profiles of kidney cancers closely correlated with their histological subtypes. We have also identified in these subtypes differentially expressed genes that could have important diagnostic and therapeutic implications.


Effect of Sildenafil Citrate on an Orthotopic Prostate Cancer Growth and Metastasis Model

We characterized the effects of sildenafil citrate on the growth and metastasis of human prostate cancer cells in nude mice. The androgen independent human prostate cancer cell line PC-3 was inoculated into the prostate of nude mice to produce orthotopic primary prostate cancers and metastases. Sildenafil citrate gavage was started on day 31 after tumor cell inoculation and given every other day 15 times (30 days). The 7 mice in the low dose group received 25 mg/kg body weight sildenafil citrate per gavage, while the 7 in the high dose group received 50 mg/kg body weight sildenafil citrate and the 9 in the control group received water. Autopsy was performed on day 75 to evaluate primary tumor growth and metastasis. Plasma cyclic guanosine monophosphate concentrations were measured after the single dose of 50 mg/kg sildenafil citrate in the mice. Plasma cyclic guanosine monophosphate concentration increased 4-fold 1 hour after sildenafil citrate administration. The plasma concentration decreased rapidly and returned to normal after 8 hours. There was no significant difference in tumor weight between any of the 3 groups. The number of metastatic lymph nodes correlated significantly with primary tumor weight (p = 0.03) with a correlation coefficient of 0.454 but there was no significant correlation between the number of involved lymph nodes and sildenafil administration. Distant metastases were not significantly promoted by sildenafil administration. Incontinuous oral administration of sildenafil citrate did not promote primary tumor growth and metastasis in an orthotopic prostate cancer model.


Strategy for treating pediatreic urological disease in the department of urology

徳島大学泌尿器科における小児泌尿器科医療の取り組み


Functional evaluation of one-stage urethroplasty with parameatal foreskin flaps repair of hypospadias using uroflowmetry

Uroflowmetry is a simple, accurate and non-invasive test. In the present study, we aimed to determine the role of uroflowmetry in the evaluation of the functional results of one-stage urethroplasty with parameatal foreskin flaps (OUPF) technique. Twenty-one children who had undergone OUPF repair at our clinic were selected. Selection criteria were that patients were toilet trained and had no fistula. Uroflowmetry was performed using a rotating disk sensor. The maximum flow rate (Qmax) and average flow rate (Qave) were plotted against body surface related flow rate nomograms. The upper 95% tolerance limits for the 5th, 10th, 15th, 20th and 25th percentiles of the normal population were used for comparison. The flow pattern was classified as bell ring, plateau or intermittent. The median age at the first uroflowmetry was 4.7 years (range 2.5-8.6) and the mean postoperative follow-up period was 25 months (range 1-58). Twelve children had Qmax above the 25th, six between the 5th and 25th and three less than the 5th percentiles of the normal population. A normal bell-shaped flow curve was obtained in 17 (80.6%) of the children. Of the three children with Qmax below the 5th percentile, two children had a plateau flow pattern and were found to have a urethal stricture. Dilation was performed successfully, after which the Qmax returned to the normal range and the symptoms disappeared. The OUPF technique provided satisfactory functional results for hypospadias repair. We advocate the use of uroflowmetry for routine postoperative follow-up.


Gene Expression Profiling of Renal Cell Carcinoma and Its Implications in Diagnosis, Prognosis, and Therapeutics

Renal cell carcinoma (RCC) is the 10th most common cancer in the United States. It is a histologically heterogeneous disease with various histologic types being characterized by distinct genetic alterations. This chapter reviews advances in the gene expression profiling of RCC and discusses their clinical implications. Data are promising, and many more RCC-related microarray studies are currently underway or in planning. Undoubtedly these data will have an impact on the diagnosis, prognosis, and treatment of RCCs in the future. Finally, this chapter discusses what additional studies should be performed to help uncover the molecular mechanisms of RCC and to bring this new knowledge into use in the clinical arena.


Gene Expression Profiling of Favorable Histology Wilms Tumors and Its Correlation with Clinical Features

The aims of this study were to understand the underlying molecular mechanisms of favorable histology Wilms tumors (WTs) and to classify them based on their molecular signatures. We studied a total of 15 favorable histology WTs using microarrays containing 19,968 cDNAs. First, we found commonly altered genes in WT. A total of 267 cDNAs were significantly overexpressed at least 3-fold in all of the tumors compared with noncancerous kidney and contained known WT-related genes such as IGF II and WT1. The gene with the highest expression change compared with noncancerous kidney was topoisomerase IIalpha. By hierarchical clustering, there was a clear distinction between high-stage and low-stage tumors. A total of 30 cDNAs were found differentially expressed between the high- and low-stage groups. One of them, Stathmin 1, which is involved in the microtubule system, was highly expressed in high-stage tumors compared with the low-stage tumors. The present chemotherapy regimens for WT consist mainly of topoisomerase II inhibitors (i.e., actinomycin D, doxorubicin, and etoposide) and antimicrotubule agents (i.e., vincristine and paclitaxel). Our data suggest that high expression of topoisomerase IIalpha and microtubule-related genes such as tubulin and stathmin 1 may be related to the high chemosensitivity of WT. In addition, retinol-related genes such as CRABP2 and retinol-binding protein 1 were overexpressed in WT, and CRABP2 was more highly expressed in the poor outcome patients, which suggests that retinoid acid may be a potential drug. In summary, our findings suggest that the integration of gene expression data and clinical parameters could aid in detecting aggressive tumors among favorable histology WT and lead to the discovery of new drugs for WT.


Laparoscopic nephroureterectomy for dysplastic kidney in children: an initial experience

Laparoscopic nephroureterectomy for dysplastic kidney is now becoming a widely accepted procedure. We report here our initial experience with laparoscopic nephroureterectomy in four girls. Between 1993 and 1999, laparoscopic nephroureterectomy was performed in four girls (mean age 5.3 years). Three patients had an ectopic dysplastic kidney with ectopic ureter, and one patient had hydronephrosis with megaureter due to distal ureteral atresia of the upper moiety in a duplicated dysplastic kidney. The transperitoneal approach was used in all cases. Mean operative time was 195 min (range 150-266). Blood loss was minimal. All operations were completed successfully and there were no intraoperative or postoperative complications except for subcutaneous emphysema in one patient (case 4). Postoperative analgesia was used in three patients and administered in the form of diclofenac sodium suppositories 12.5 mg (cases 1 and 2) or acetaminophen suppositories 50 mg (case 3) for 1-2 days. One patient did not require any analgesia (case 4). Oral fluid intake was resumed on the first postoperative day and ambulation began within 1-3 days (mean 1.6, cases 1, 2 and 3) and 6 days (case 4). All children returned to normal activity within 3-6 days of surgery. Mean postoperative hospital stay was 7.3 days. All cases had uneventful courses after discharge. Laparoscopic nephroureterectomy can be performed safely, with minimal postoperative pain, excellent cosmetic results and early ambulation. We advocate the use of laparoscopy for the diagnosis and treatment of dysplastic kidney with ectopic ureter.


Prognostic Significance of matrix metalloproteinase-2 activation ratio in renal cell carcinoma

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. MMP-2 and MMP-9 have been reported to be closely associated with tumor invasion and metastasis in various human carcinomas. Tissue samples were obtained from 57 patients with renal cell carcinoma (RCC) who underwent radical nephrectomy in our hospital. We examined the expression of MMPs by gelatin zymography and assessed correlations with clinico-pathological parameters and clinical outcomes. We detected bands corresponding to MMP-9, proMMP-2 and active MMP-2. The expression of active MMP-2 and MMP-2 activation ratio (active MMP-2/[proMMP-2 and active MMP-2]) were higher in T3 tumors than in T1 and T2 tumors. There were no significant differences in the expression of proMMP-2, active MMP-2 or MMP-9 for any of the clinico-pathological parameters. Patients with high MMP-2 activation ratio or high MMP-9 had significantly worse cause-specific survival. Interestingly, among patients with stage III RCC, those with high MMP-2 activation ratio or high active MMP-2 had significantly worse cause-specific survival. Univariate analysis showed that histological grade (P = 0.0001), histologic type (P = 0.0005), MMP-2 activation ratio (P = 0.0159), stage (P = 0.0001), MMP-9 (P = 0.0316), and T (primary tumor) category of TNM (primary tumor, lymph node, metastasis) classification (P = 0.0021) were significant predictors of clinical outcome. Multivariate analysis showed that only histological grade (P = 0.002) and stage (P = 0.0099) were independently significant predictors of clinical outcome. Activation of MMP-2 appears to play important roles in initiating metastasis, as shown by results obtained with stage III RCC patients. However, further study is needed to confirm this.


Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification

To better understand the molecular mechanisms that underlie the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC), we studied the gene expression profiles of 29 ccRCC tumors obtained from patients with diverse clinical outcomes by using 21,632 cDNA microarrays. We identified gene expression alterations that were both common to most of the ccRCC studied and unique to clinical subsets. There was a significant distinction in gene expression profile between patients with a relatively nonaggressive form of the disease [100% survival after 5 years with the majority (15/17 or 88%) having no clinical evidence of metastasis] versus patients with a relatively aggressive form of the disease (average survival time 25.4 months with a 0% 5-year survival rate). Approximately 40 genes most accurately make this distinction, some of which have previously been implicated in tumorigenesis and metastasis. To test the robustness and potential clinical usefulness of this molecular distinction, we simulated its use as a prognostic tool in the clinical setting. In 96% of the ccRCC cases tested, the prediction was compatible with the clinical outcome, exceeding the accuracy of prediction by staging. These results suggest that two molecularly distinct forms of ccRCC exist and that the integration of expression profile data with clinical parameters could serve to enhance the diagnosis and prognosis of ccRCC. Moreover, the identified genes provide insight into the molecular mechanisms of aggressive ccRCC and suggest intervention strategies.

Proceedings of the National Academy of Sciences of the United States of America


Secondary amyloidosis of the bladder causing macroscopic hematuria

Bladder involvement in amyloidosis is unusual. The case of an 80-year-old man with macroscopic hematuria caused by secondary amyloidosis of the bladder is described. Cystoscopic examination revealed only a diffuse edematous area and bleeding. No tumor-like lesions were identified. Transurethral biopsy revealed amyloid deposits. Macroscopic hematuria disappeared spontaneously after cystoscopy and bladder biopsy. The patient has been followed up without treatment and is currently free of symptoms.


Association of a novel constitutional translocation t(1q;3q) with familial renal cell carcinoma

Four cases of late onset clear cell renal cell carcinoma (RCC), a case of gastric cancer, and a case of exocrine pancreatic cancer were identified in a Japanese family. In order to elucidate the underlying mechanism for tumorigenesis in this family, extensive genetic studies were performed including routine and spectral karyotyping (SKY), fluorescence in situ hybridisation (FISH), comparative genomic hybridisation (CGH), loss of heterozygosity studies (LOH), and VHL mutation analysis. A germline translocation t(1;3)(q32-q41;q13-q21) was identified by karyotyping in five members of the family including all three RCC cases tested. The translocation was refined to t(1;3)(q32;q13.3) by FISH analysis using locus specific genomic clones, and the two breakpoints were mapped to a 5 cM region in 3q13.3 and a 3.6 cM region in 1q32. Both CGH and allelotyping using microsatellite markers showed loss of the derivative chromosome 3 carrying a 1q segment in the three familial RCCs analysed. Additional chromosomal imbalances were identified by CGH, including amplifications of chromosomes 5 and 7 and loss of 8p and 9. No germline VHL mutation was found but two different somatic mutations, a splice (IVS1-2A>C) and a frameshift (726delG), were identified in two RCCs from the same patient confirming their distinct origin. Taken together, these results firmly support a three step model for tumorigenesis in this family. A constitutional translocation t(1q;3q) increased the susceptibility to loss of the derivative chromosome 3 which is then followed by somatic mutations of the RCC related tumour suppressor gene VHL located in the remaining copy of chromosome 3.


De-epithelialized flap for closure of urethrocutaneous fistula after hypospadias repair

尿道下裂形成手術後の尿道皮膚瘻に対するde-epithelialized flapを用いた瘻孔閉鎖術の検討

日本小児泌尿器科学会雑誌


Analysis of serum soluble interferon α/β receptor levels in patients with urological diseases

泌尿器科疾患における血清中可溶性インターフェロンα/βレセプターの意義

(Purpose)In order to define the clinical significance of serum soluble Interferon α/βreceptor(sIFN/α/βR)levels, we determined sIFNα/βR concentrations in serum of patients with urological benign and malignant diseases. (Materials and Methods)Serum sIFNα/βR levels were measured in normal control(n=22), patients with benign diseases(n=50)included urolithiasis(n=16), prostatic hypertrophy(n=13), and malignant diseases included bladder cancer(n=49), renal cell carcinoma(n=30)and prostate cancer(n=36)by the enzyme linked immunosolbent assay(ELISA)using monoclonal and pliyclonal antibodies. The levels of serum sIFNα/βR was correlated with the results of other hematoserological examinations, and clinical or pathological characters of each urological malignancies. (Results)The serum sIFNα/βR levels(pg/ml)of patients with urolithiasis(2,370.6±640.6, p=0.0002), benign prostatic hypertrophy(2,121.1±55.06, p=0.0103), bladder cancer(2,512.3±1,012.3,p=0.0006), renal cell carcinoma(2,686.4±1,510.9, p=0.0046), prostate cancer(3,188.7±1,788.0, P=0.0003)showed significantly higher values than those of controls(1,790.5±346.7). Moreover, we found statistically significant correlations among serum creatinine(Cr)levels and sIFNα/βR levels. However, there were no correlations between the sIFNα/βR levels and clinical stage, or histological grade in the patients with bladder cancer or prostate cancer, whenever the levels of sIFNα/βR were corrected by serum Cr levels. On the other hand, high level of corrected serum sIFNα/βR was observed in patients with high stage or high grade renal cell carcinoma, but not significant statistically. (Conclusion)Elevated serum sIFNα/βR was observed in patients with urological decease. Further examinations should be necessary to determine the clinical usefulness of serum sIFNα/βR.

(目的)泌尿器科疾患における可溶性インターフェロンα/βレセプター(soluble Interferon-α/βreceptor:sIFNα/βR)に関する検討はまだ十分なされていない．今回,ポリクローナル抗体およびモノクローナル抗体を用いたサンドイッチEnzyme Linked Immunosolbent Assay(ELISA)法による細胞膜外部分のsIFNα/βRの測定系が確立されたので,各種泌尿器科良性疾患,膀胱癌,腎細胞癌,前立腺癌の血清中sIFNα/βRを測定し臨床的意義について検討を行った．(対象と方法)健常コントロール22例,良性疾患50例(尿路結石症16例,前立腺肥大症13例,その他21例),膀胱癌49例,腎細胞癌30例,前立腺癌36例を対象として,血清中sIFNα/βR値をELISA法により測定した．臨床検査値との相関,各疾患群における血清中sIFNα/βR値の比較,さらには悪性腫瘍患者における臨床病理像との比較解析を行った．(結果)各疾患における血清中sIFNα/βR値(pg/ml)は,健常コントロール(1,709.5±346.7)に比し,尿路結石症(2,370.6±640.6,p=0.0002),前立腺肥大症(2,121.1±550.6,p=0.0103),膀胱癌(2,512.3±1,012.3,p=0.0006),腎細胞癌(2,636.4±1,510.9,p=0.0046),前立腺癌(3,188.7±1,788.0,p=0.0003)ともに,有意に高値を示した．各種血液学的検査結果との比較では,血清中クレアチニン値との相関が認められたが,その他の検査結果との相関は認めなかった．また,血清中sIFNα/βR値と膀胱癌および前立腺癌における臨床病理像との比較では,実測値および血清中クレアチニン値による補正値(Cr補正値)ともに有意な相関は認めなかった．一方,腎細胞癌では,進行例および異型度の強い症例においてCr補正値が高値を示したが,統計学的に有意ではなかった．(結論)血清中sIFNα/βR値は各種泌尿器科疾患において高値を示した．血清中sIFNα/βR値の臨床応用の可能性を評価するためには,今後さらに多数例における詳細な検討が必要と思われた．


The role of the activated form of matrix metalloproteinase-2 in urothelial cancer

To investigate the expression of matrix metalloproteinase-2 (MMP-2, reportedly associated with cancer cell invasion and metastasis in many human cancers) in urothelial tumours and thus define its role in this disease. Materials and methods The expression of both the activated form of MMP-2 and total MMP-2 (activated + latent form) was measured using gelatine zymography in tissue obtained surgically from 61 patients with urothelial cancer. The correlation between the level of the activated form of MMP-2 and clinical and histological variables was assessed. The expression of activated and total MMP-2 were significantly higher in invasive tumour tissue and both levels were correlated with histological grade. In particular, the level of activated MMP-2 was more closely correlated than that of total MMP-2 in invasive tumour tissue. Moreover, high levels of activated MMP-2 were strongly associated with shorter disease-specific survival (P = 0.0016). These findings suggest that activated MMP-2 plays a significant role in invasion of urothelial cancer and that the level of activated MMP-2 expression is a useful prognostic indicator.


Clinicopathological review of pediatric patients with a undescended testis

停留精巣の臨床病理学的検討

日本小児泌尿器科学会雑誌


Two Cases of Robot-Assisted Total Pelvic Exenteration and Intracorporeal Ileal Conduit for Locally Advanced Rectal Cancer

局所進行直腸癌に対してロボット支援骨盤内臓全摘除術および体腔内回腸導管造設術を施行した2例

We describe two cases of locally advanced rectal cancer (LARC) treated with robot-assisted total pelvic exenteration (Ra-TPE) and intracorporeal ileal conduit (ICIC). The first case was in a 71-year-old man with LARC (RbP, T4bN2bM0, cStage IIIc). He was started on bevacizumab+S-1/oxaliplatin therapy in July 2019. In April 2020, he developed Fournier's gangrene due to subcutaneous penetration of rectal cancer. Emergency drainage and colostomy were performed simultaneously, and a percutaneous vesical fistula was created. In May 2020, Ra-TPE and ICIC were performed. Histopathological analysis revealed moderately differentiated tubular adenocarcinoma (ypT3N0, RM0). At postoperative 9 months, thoracoscopic right upper lobectomy was performed for a right metastatic lung tumor. At present, ie, at postoperative 12 months, the patient has been free of recurrence and metastasis, with a carcinoembryonic antigen (CEA) level of 1.4 ng/ml and carcinoma antigen (CA) 19-9 level of 11 U/ml. The second case was in a 61-year-old man with fistula-associated anal cancer (PRb, T4N3M1b, cStage IVb). In April 2019, he was started on FOLFOXIRI+cetuximab therapy. In August 2020, Ra-TPE, ICIC, and transperineal total mesenteric excision were performed. Histopathological analysis revealed adenocarcinoma (ypT4N0, RM0). At postoperative 11 months, thoracoscopic left lower lobectomy was performed for a left metastatic lung tumor. At present, ie, at postoperative 12 months, the patient remains free of recurrence and metastasis, with a CEA level of 7.3 ng/ml and CA19-9 level of 12 U/ml. Ra-TPE, which allows transperineal removal of a specimen, can be performed as a minimally invasive surgery in combination with ICIC.

症例1は71歳男性で，局所進行直腸癌の診断で化学療法および放射線療法を併用し，8コース終了時にPRであった．その後，直腸癌の皮下穿通による外陰部壊死性筋膜炎を発症し，緊急切開ドレナージ，S状結腸ストーマ造設術および経皮的膀胱瘻造設術を施行し，翌月に根治療法としてロボット支援骨盤内臓全摘術(Ra-TPE)，体腔内回腸導管造設術(ICIC)，創閉鎖術を施行した．病理組織結果はmoderately differentiated tubular adenocarcinoma，ypT3N0，RM0であり，術後31日目に退院した．症例2は61歳男性で，痔瘻癌に対しFOLFOXIRI+Cetuximabを計14コース施行後，FOLFIRI+Panitumumabを計14コース施行し，Ra-TPEとICIC，経会陰的直腸間膜切除術を施行した．病理診断はAdenocarcinoma，ypT4N0，RM0であり，術後36日目に退院した．両症例とも肺転移を認め胸腔鏡下肺部分切除術を施行したが，術後12ヵ月時点でその他の転移や局所再発は認めていない．


腎移植後のリンパ漏にリンパ管造成が効果的であった3例

腎移植後のリンパ漏にリンパ管造成が効果的であった3例


Injury of spleen, pancreas, and bowel during laparoscopic adrenalectomy or nephrectomy

術中合併症を回避するための方法と対処法 臓器損傷を回避するための注意点 副腎・腎摘除術における脾臓・膵臓・腸管損傷


徳島大学泌尿器科におけるBCG膀胱内注入療法の臨床検討

徳島大学泌尿器科におけるBCG膀胱内注入療法の臨床検討


子宮頸癌副腎転移との識別が困難であった18F-FDG PET/CT陽性副腎皮質線種の1例


限局性前立腺癌に対する密封小線源療法のリスク分類別治療成績

限局性前立腺癌に対する密封小線源療法のリスク分類別治療成績


射精障害を契機に発見されたトルコ鞍空洞症を伴う汎下垂体機能低下症の1例

射精障害を契機に発見されたトルコ鞍空洞症を伴う汎下垂体機能低下症の1例


BCG膀胱内注入療法後に生じたReiter症候群の1例

BCG膀胱内注入療法後に生じたReiter症候群の1例


Training system of laparoscopic surgery for young urologists in the university of Tokushima

効果的効率的な泌尿器腹腔鏡手術医の育成 徳島大学における泌尿器腹腔鏡技術認定医の育成に対する試み


Long-term recurrence-free survivor after laparoscopic removal of solitary adrenal metastasis from endometrial adenocarcinoma.

Solitary adrenal metastasis from endometrial adenocarcinoma is extremely rare. We report herein the case of a laparoscopically resected solitary adrenal metastasis originating from endometrial adenocarcinoma. The patient was a 55-year-old woman who had undergone total abdominal hysterectomy for stage IIIc endometrial carcinoma, followed by 7 courses of adjuvant chemotherapy comprising carboplatin and paclitaxel. However, the patient developed an isolated right adrenal metastasis 15 months postoperatively. The solitary adrenal metastasis (diameter, 5.7 cm) was removed laparoscopically. The patient has now been in good health without recurrence for 5 years and 7 months after laparoscopic surgery. To the best of our knowledge, this is the first case of solitary adrenal metastasis originating from endometrial adenocarcinoma that is controlled for the long term by successful laparoscopic resection.

The Journal of Medical Investigation : JMI


The role of actinin-4 in bladder cancer invasion.

To examine actinin-4 expression levels in bladder cancer, in particular its levels during cellular growth and invasion. Actinin-4 is an actin-binding protein that is associated with cell motility and cancer metastasis.