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Novel androgen receptor axis-targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs.We previously performed a multicenter study to identify prognostic factors for metastatic hormone-sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3-year OS (PROSTAT-BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group.The predictors were age (71.4 years), serum levels of C-reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not.The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high-risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs.

Supplemental Fig. 2. A: An example (A-5847) of tracing an adrenal section. An arrowhead indicates the portion of the enlarged image in panel B. The area of the section was measured in a similar manner to tracing using CYP11B2-stained sections. C: Weakly positive cells, positive cells, and strongly positive cells were colored in yellow, orange, and red, respectively, in the example image in panel A. Their areas were used to measure positivity, which was automatically performed using the algorithm “Positive Pixel Count 2004-08-11” in ImageScope software (version12.2.1.5005, Aperio). The arrowhead shows the enlarged image in Panel D. E: An example of tracing APCCs (black lined areas), which was performed by KM on a CYP11B2-stained section of sample A-5797.

Supplemental Figure 1. All images. Scanned images of CYP11B2 staining (left columns), H&E (middle columns), and HSD3B2 staining (right columns). Case number, block number, staining methods, and section numbers (5 digits) are labeled below each image. Bars indicate 5 mm.

Generation of hybridoma cells producing a mouse anti-human CYP11B2 monoclonal antibody

Supplemental Figure 3. Correlations between 3 examiners. Correlations of NOA (/mm2) between KN vs KM (A), KN vs GAE (B), and KM vs GAE (C), as well as those of AA/WAA (%) between KN vs KM (D), KN vs GAE (E), and KM vs GAE (F). r and p values were calculated by Pearson’s product moment correlation analysis.

A 75-year-old Japanese male was referred to our institution for the evaluation of a left ureteral tumor in the ureterovesical junction. Computed tomography and pathologic examination under ureteroscopy revealed an invasive left ureteral urothelial carcinoma with left obturator nodal metastasis without distant metastasis. First, the patient underwent systemic chemotherapy (gemcitabine and cisplatin chemotherapy). We then performed left radical nephroureterectomy and extended lymph node dissection. Pathological examination revealed that the tumor was a high-grade invasive urothelial carcinoma with left common iliac and pelvic lymph node metastasis (pT3N2). Unfortunately, metastases appeared in the common iliac and para-aortic lymph nodes immediately after the operation; therefore, the previous first-line chemotherapy was readministered and second-line chemotherapy (gemcitabine and paclitaxel chemotherapy) was also performed. We also performed consolidative radiotherapy and salvage radiotherapy (boost, 20 Gy/10 fractions to the inferior para-aortic, and left common iliac regions containing swollen lymph nodes). The patient has shown no evidence of recurrence or metastasis even approximately 4 years after the initial diagnosis of advanced UUT-UC with lymph node metastasis. Our case suggests that consolidative or salvage radiotherapy combined with surgery and chemotherapy may provide clinical benefit for selected cases of advanced UUT-UC with lymph node metastasis.

第45回 尿路悪性腫瘍研究会 2018年7月21日 講演スライド

Supplemental Figure 1. All images. Scanned images of CYP11B2 staining (left columns), H&E (middle columns), and HSD3B2 staining (right columns). Case number, block number, staining methods, and section numbers (5 digits) are labeled below each image. Bars indicate 5 mm.

A 67-year-old female patient had a cystic mass, 6 cm in diameter, which was incidentally detected on the dorsal side of the cecum in the retroperitoneum. A laparoscopic tumor excision was performed. Microcopically, the majority of the cystic wall consisted of Mullerian type serous epithelium, partially including the columnar epithelium containing round nuclei and mucin production. The columnar epithelium was similar to the uterocervical epithelium, and there was proliferation of dense collagen fibers resembling ovarian stroma under the epithelium. These microscopic findings were consistent with ovarian seromucinous cystadenoma. Therefore, the cyst was diagnosed to be a retroperitoneal Mullerian cyst. This is the 15th case of a cyst of this type reported and is the first case in which a laparoscopic excision was performed.

Pheochromocytoma occurs in 0.1 to 5.7% of patients with type 1 neurofibromatosis (NF1). Radiological findings of pheochromocytoma are often similar to those of neurofibroma ; therefore, any pheochromocytoma should be excised in hypertensive patients with NF1. A 60-year-old male patient with NF1 was referred to this hospital for an incidentally discovered right adrenal mass, 7×6 mm indiameter. The patient had multiple benign tumors and suffered from hypertension for 4 years. Laboratory findings showed increased serum and urine catecholamine levels. Magnetic resonance imaging (MRI) revealed a high signal intensity on T2-weighted images, which was enhanced by gadolinium contrast. The mass was positive for 131 I-metaiodobenzylguanidine (MIBG) scintigraphy. A laparoscopic adrenalectomy was performed. A histopathological diagnosis of pheochromocytoma was made. The patient's post-operative course was uneventful, and blood pressure was normalized. Screening of the adrenal tumor is strongly recommended for NF1 patients with hypertension, since any unfavorable events due to catecholamine such as cardiomyopathy and fatal arrhythmia can be avoided by adequate surgical intervention.

Penile strangulation is one of the emergent urologic disorders, because immediate release is the critical treatment to prevent penile necrosis, urethral injury, erectile disorder, and other unfavorable events. A 66- year-old man was transferred to the emergency room of our hospital for the penile swelling and pain, occurring by penile insertion to the beverage bottle for masturbation. The penis was completely relieved using an electric plaster cutter without any injury. The strangulation time was four hours and a half, and there were no complications. We recommend an electric plaster cutter as a useful tool for this incident.

Intrascrotal fibrous pseudotumor is rarely observed, and only 40 cases have been reported in Japan. A 65-year-old male patient visited this hospital due to a painless right scrotal mass. Computed tomography demonstrated a solid mass with a cystic component ; however, the exact location of the mass in relation to other scrotal contents was not determined. Intraoperative findings revealed a solid mass, 2 cm in diameter, in the tunica vaginalis. The mass could not be dissected from the epididymis ; therefore, high orchiectomy was indicated. A histopathological diagnosis of fibrous pseudotumor was made. The patient's postoperative course was uneventful, and no recurrence has been found. It is difficult to make a diagnosis of paratesticuler tumor based on preoperative radiological results and even macroscopic observation during surgery. We strongly recommend that it is necessary to undergo high orchiectomy for a fibrous pseudotumor in which dissection from the peripheral tissue is very difficult since it may involve various types which may lead to a diagnosis of malignancy.

We encountered a case of lipomatous tumor in the left scrotum, which was clinically and radiologically quite similar to an inguinal hernia. A 75-year-old male patient visited a nearby hospital complaining of a painless left scrotal swelling. Palpation revealed an elastic firm mass 5 cm in diameter in the left scrotum. The tumor marker levels were within the normal range. The patient was referred to our hospital for further evaluation. A preoperative diagnosis of inguinal hernia containing the omentum was made. Although a solid mass was demonstrated in the scrotum, no inguinal hernia was found at the operation. Therefore, a left high inguinal orchiectomy was performed. Microscopically, most of the tumor consisted of mature adipocytes, some of which had different cellular sizes. Scattered lipoblasts and atypical mesenchymal spindle cells were also observed, suggesting potential malignancy.

We encountered a case of seminoma arising from an intra-abdominal cryptorchidism associated with ipsilateral renal agenesis. A 42-year-old male patient was referred to this hospital with a complaint of right upper abdominal distention with pain. Radiologic examination demonstrated a right retroperitoneal mass, 12 cm in diameter, while the ipsilateral kidney was not detectable. Intra-aortocaval lymphnodes were swollen at the renal hilus level. The patient underwent tumor resection and lymphadenectomy. A histopathological diagnosis of seminoma with para-aortic lymphnode involvement was made. A definite diagnosis was seminoma (pT1 pN3M0) arising from cryptorchidism associated with right renal agenesis. The present case is the third of its kind reported in the literature.

A 30-year-old male, who underwent orchiopexy of left undescending testis in his childhood, presented with right hemiscrotal swelling without pain. Ultrasonography revealeda paratesticular tumor which showedenhancement on magnetic resonance imaging (MRI). Diffusion-weightedMRI showedd ecreased diffusion in the tumor, andmalignant tumor couldnot be ruledout. High inguinal orchiectomy was carried out and pathological diagnosis was benign leiomyoma of the epididymis.

74歳男。患者は膀胱腫瘍の診断で, 膀胱全摘除術と代用膀胱造設術が施行され, 病理組織診断で周囲脂肪織に若干の癌浸潤が認められた。術後の化学療法は患者の意向で施行せず, 経過は良好であったが, 術後11ヵ月, 排便困難および肛門からの持続的な粘液の流出が出現し, 大腸イレウスの診断で緊急入院となった。注腸造影では下部直腸から口側に約15cmの狭窄が認められ, MRIでは直腸粘膜, 筋層の全周性の肥厚を認めたが, 明らかな腫瘤は認めなかった。人工肛門造設術と直腸生検を施行したところ, 病理組織学的には直腸筋層内に膀胱癌の浸潤を認めたが, 直腸粘膜内には癌細胞を認めなかった。MVAC療法を開始したが副作用が強く, 中止となり, シスプラチン併用放射線照射が施行された。だが, 大臀筋層内に膀胱癌の転移がみられ, 徐々に全身状態が悪化して, 患者は最終的に死亡となった。, Recurrent urothelial carcinoma of the bladder is often a locally progressive disease. Invasive bladder cancers frequently show lymphatic or hematogenous metastasis. Regional lymph node metastasis is a frequent finding and may be the first sign of recurrence. Rectal involvement and obstruction is rare, but metastasis to the colon, small intestine, and stomach have been reported. Here, we report an unusual case of urothelial carcinoma of the bladder manifesting as an annular rectal obstruction.

79歳男.約10年前に膀胱癌に対して膀胱全摘術, 舟状窩以外の尿道摘除術と回腸導管増設術を施行し, 追加治療は行わず経過観察となっていたが, CTで左鼠径部リンパ節腫大を指摘された.経過観察となったが, 増大傾向を認めたため膀胱癌術後左鼠径部リンパ節転移と診断し, 鼠径部リンパ節摘除術を施行した.術後は全身化学療法を希望せず経過観察となったが, 胸部X-P上で肺転移が指摘された.更に, 左鼠径部のリンパ節腫大が再発し, 摘出術を行ったが, 肺転移の増悪とリンパ節腫大の再発を認め, 化学療法は効果なく, 亀頭部先端の乳頭状腫瘤も指摘された.その後, 全身状態が徐々に悪化し, 呼吸不全で死亡した, A 79-year-old man had undergone radical cystourethrectomy for bladder carcinoma in January, 1989. Pathological report was Small cell carcinoma (SCC) >> transitional cell carcinoma (TCC), G2 > G3, pT4 (prostate), ew (-). Ten years later, follow-up computed tomography (CT) revealed swollen left inguinal lymph node in October 1998 and lymph node dissection was performed in January, 2000. The pathological report showed TCC, G2. Left inguinal lymph node metastases appeared again in January, 2001. Chest X-ray films showed multiple lung metastases in March, 2001. Three couses of MVAC (methotrexate, vinblastine, doxorubicin cisplatinum) chemotherapy had been performed since September, 2001 but were in effective. Papillary tumor was observed at external urethral meatus in September, 2002 and the biopsied specimens showed TCC, G1 > G2, pathologically. Finally he died of respiratory insufficiency in January, 2003. It is suggested that the recurrent TCC tumor in the urethral remnants might metastasize into the inguinal lymph nodes.