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.


The role of expression of vascular endothelial growth factor isoforms and platelet-derived endothelial cell growth factor in bladder cancer.


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．


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


後期研修医がおさえておきたい泌尿器疾患TOP30 尿路造影

後期研修医がおさえておきたい泌尿器疾患TOP30 尿路造影


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


Symposium: Next generation surgical treatment

シンポジウム1 次世代の外科治療


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


Late recurrence of renal cell carcinoma: retrospective and collaborative study of the Japanese Society of Renal Cancer.

To evaluate in collaboration the clinical features of late recurrence of renal cell carcinoma (RCC). Late recurrence is one of the specific biologic behaviors of RCC; however, the clinical and pathologic features of the late recurrence of RCC are not fully understood.


Phase III trial of everolimus in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from RECORD-1.

To assess the efficacy and safety of everolimus in Japanese patients with metastatic renal cell carcinoma.


Three-dimensional CT cavernosography: reconsidering venous ligation surgery on the basis of the modern technology.

To examine the feasibility of three-dimensional (3D) CT cavernosography in the diagnosis of corporal veno-occlusive dysfunction.


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


Clinical significance of Galectin-3 in clear cell renal cell carcinoma.

Overexpression of galectin-3 in a variety of cancer cell lines has been shown to correlate with tumor progression and metastasis. In this study, we investigated the expression of galectin-3 in clear cell renal cell carcinoma (CC-RCC) and evaluated the relationship between galectin-3 expression levels and the clinicopathological features of CC-RCC. Expression of galectin-3 in the kidney cancer cell lines Caki-1, Caki-2, A704, ACHN and KPK-1 were evaluated using western blot analysis, while galectin-3 expression in CC-RCC tissues and normal parenchyma were measured by real-time PCR and immunohistochemistry. We found that galectin-3 was overexpressed in the Caki-1, Caki-2, A704, ACHN and KPK-1 cell lines and that the expression level in CC-RCC was also significantly higher than that in renal parenchyma obtained from the same patient samples (p=0.039). Galectin-3 expression in CC-RCC with distant metastasis was also significantly higher than that in CC-RCC without distant metastasis (p=0.045). In conclusion, we revealed that galectin-3 is highly expressed in CC-RCC, especially in CC-RCC with distant metastasis, suggesting that galectin-3 may serve as a novel target molecule for predicting CC-RCC metastasis.

The Journal of Medical Investigation : JMI


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 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.


Mass screening for prostate cancer in Tokushima city - Analysis of the 3 year results from 2001 to 2003 -

徳島市前立腺がん検診―平成13∼15年度3年間の比較検討―