Clinical, pathological, and therapeutic features of newly diagnosed prostate cancer predominantly detected by opportunistic PSA screening: A survey of Shiga Prefecture, Japan.

BACKGROUND: In all the prefectures of Japan, with the exception of Shiga Prefecture, more than half of local governments have an organized prostate-specific antigen (PSA) screening system in place. However, in the Shiga Prefecture, only a single city performed PSA screening over the time period of this survey. The purpose of the present study was to determine the clinical, pathological, and therapeutic features of newly diagnosed prostate cancer in localities where a formally organized screening system was almost entirely absent. METHODS: A multicenter observational study was conducted in the Shiga Prefecture, which has the lowest rate of population-based PSA-screening in Japan. Patients' age, initial PSA, reasons for PSA testing, Gleason score, clinical stage, and primary treatments were surveyed. We stratified patients according to the reasons for PSA measurement, and compared the differences between groups subject to organized versus opportunistic screening. RESULTS: In the 2 years 2012 and 2017, 984 newly diagnosed prostate cancer patients were analyzed. Of these, 954 (97%) were opportunistically tested (i.e., not as part of an organized screening system), with the remaining 29 (3%) measured as part of an organized screening program. Patients in the former group exhibited a higher initial PSA value than in the organized screening group (median: 11.49 vs. 5.67 ng/ml). They also had worse clinical features, including higher Gleason score and TNM stage. More patients in the organized screening group were treated curatively than in the nonorganized screening group in terms of the primary treatment. The results were similar in a subanalysis of the patients of age 50-69 years. CONCLUSIONS: Organized PSA screening contributes to increasing the number of patients diagnosed with early-stage cancer who can be treated curatively.

[The Combination Therapy of Gemcitabine Plus Paclitaxel Induced Complete Response in a Tongue Skin Brain Metastasis of Bladder Carcinoma: A Case Report].

Tongue, skin and brain metastases of bladder cancer are very rare and few cases have been reported. We report a case of tongue, skin and brain metastases of bladder cancer. A 61-year-old woman was referred to our hospital with gross hematuria. Transurethral resection of the bladder (TURBT), tongue biopsy and skin biopsy were performed. Pathological findings showed urothelial carcinoma, G2, micro papillary variant, pT2＞ and tongue and skin metastases from urothelial carcinoma of bladder. After three cycles of chemotherapy (gemcitabine plus paclitaxel), tongue and skin metastases disappeared. Cystoscopy revealed no tumor of bladder. Eleven months later, she was admitted to our hospital because of disturbance of consciousness. Magnetic resonance imaging (MRI) showed multiple brain metastases. Rechallenge of chemotherapy (gemcitabine plus paclitaxel) restored from disturbance of consciousness and MRI showed partial response of brain metastases. We performed six additional courses of chemotherapy. Skin, tongue and brain metastases from bladder cancer indicate poor risk. Chemotherapy (gemcitabine plus paclitaxel)could be effective against these matastases.

Recurrent rhabdomyosarcoma after adjuvant chemotherapy for stage I non-seminomatous germ cell tumor with malignant transformation.

We report a rare case of stage I non-seminomatous testicular germ cell tumor with malignant transformation. The patient received two cycles of chemotherapy (cisplatin, bleomycin and etoposide) tailored to testicular germ cell tumors as an adjuvant therapy after orchiectomy. However, 22 months later, the patient developed a metastasis in the occipital region that consisted of solely rhabdomyosarcoma through malignant transformation of a teratoma component. This case highlights an issue related to adjuvant chemotherapy for testicular germ cell tumors with components of malignant transformation.

[Repair of right ureteral stenosis by traumatic injury with appendiceal interposition: a case report].

We report a repair of a right ureteral stenosis with the appendix as a ureteral substitute. A 20-year-old male suffered a traumatic injury in a motorcycle accident. He underwent an emergency operation for right hemothorax, intraabdominal hemorrhage, and bone fracture of right leg. Three weeks later, right hydronephrosis and urinoma were identified. Combined retrograde and antegrade pyelography demonstrated a severe 7 cm long stenosis in the right upper ureter. After an indwelling right nephrostomy catheter was placed, he returned to the hospital for a ureteral reconstruction. We planned to substitute the appendix to bridge the stenotic ureter. After transecting the appendix from the cecum, the mesoappendix was spatulated from mesoileum. Ureteral tissue was resected and appendix was interposed. Three weeks later, ureteral stent was removed. DTPA diuretic renogram scintigraphy demonstrated no evidence of obstruction five weeks later. Two years postoperatively, the patient was asymptomatic and his renal function was normal. Although only few cases of ureteral repair with appendix are known, uretero-appandix replacement is less invasive and complicated, and recommended in some cases.

Population­based prostate­specific antigen screening for prostate cancer may have an indirect effect on early detection through opportunistic testing in Kusatsu City, Shiga, Japan.

Prostate cancer is the most common genitourinary cancer in men. Population-based serum prostate-specific antigen (PSA) testing is used to screen men for the early detection of asymptomatic prostate cancer. The present study compared the features of patients with prostate cancer in Kusatsu City, the only municipality in Shiga Prefecture of Japan to implement organized PSA screening, with those in other municipalities. The target population for organized PSA screening by mail invitation was men ≥50 years. Patients were pathologically diagnosed via prostate biopsy because of elevated serum PSA. This multicenter observational study was subsequently conducted in 14 hospitals. The following information was extracted from patient records: age, reason for PSA testing, initial PSA level, Gleason score, clinical stage, and place of residence. Risk classification was defined as low, intermediate, high, and advanced. Each patient was stratified according to their city/town. A total of 984 patients diagnosed with prostate cancer in Shiga in 2012 and 2017 were analyzed, of which 955 (97%) were opportunistically tested, with the remaining 29 (3%) assessed by organized screening. In Kusatsu, 93 patients were diagnosed, of whom 26 (28%) were detected by organized screening. By contrast, only three of 891 patients (0.3%) were detected by organized screening in other municipalities. Of patients in Kusatsu, cases identified by opportunistic testing had a higher initial PSA value (P=0.010) than those identified by organized screening. However, patients detected through opportunistic testing in Kusatsu City were younger (P=0.034), had a lower PSA value (P=0.001), and improved risk classification (P<0.001) than those in other municipalities. It was concluded that more patients were diagnosed with early-stage cancer by organized PSA screening. Furthermore, population-based PSA screening in Kusatsu City may have indirectly affected early detection, even by opportunistic testing.

Methylation profile of DNA repetitive elements in human testicular germ cell tumor.

Testicular germ cell tumors (TGCTs) have a unique epigenetic profile distinct from that of other types of cancer. To further evaluate epigenetics of TGCTs, this study examines DNA methylation patterns of DNA repetitive elements in TGCTs. Bisulfite genomic sequencing and combined bisulfite restriction analysis (COBRA) were used to analyze the methylation patterns of DNA repetitive elements (LINE1 and Alu repeats) in embryonal carcinoma (EC) derived cell lines, primary TGCT tissues, noncancerous testicular tissues adjacent to TGCTs and cancer cells derived from somatic tissues (testicular malignant lymphoma tissues and renal cell carcinoma cell lines). Through both bisulfite genomic sequencing and COBRA, LINE1 was extensively hypomethylated in both seminomatous and nonseminomatous TGCT tissues as well as EC cell lines. We studied two Alu repeats locating in the 5' end of E-cadherin and XIST by bisulfite genomic sequencing. These two Alu elements were extensively hypomethylated in seminomatous TGCTs, but methylated in nonseminomatous TGCTs, including two EC derived cell lines. This increased unmethylated profile in seminomatous TGCTs was observed also by COBRA for Alu repeats. Although partial demethylation of DNA repetitive elements was observed in cancer cells of somatic tissue origin, the degree of demethylation was more pronounced in TGCTs than in cancer cells of somatic tissue origin. We observed abnormal demethylation of DNA repetitive elements in some of the tissues adjacent to TGCTs. The results indicate that the underlying mechanisms to undergo or maintain demethylation of DNA repetitive sequences differ between TGCTs and cancer cells of somatic tissue origin.

Therapeutic potential of SOX2 inhibition for embryonal carcinoma.

PURPOSE: Some nonseminomatous germ cell tumors are resistant to any type of chemotherapy. Control of embryonal carcinoma cells is crucial to manage nonseminomatous germ cell tumors. We established SOX2 targeting therapy in an embryonal carcinoma model. MATERIALS AND METHODS: SOX2 expression was evaluated in a series of testicular germ cell tumor tissue samples. The antitumor effect of SOX2 knockdown was analyzed in vitro and in vivo using an embryonal carcinoma model. RESULTS: In testicular germ cell tumor tissue SOX2 was expressed in the foci of embryonal carcinoma but negative in seminoma and yolk sac tumors. In an embryonal carcinoma model SOX2-siRNA induced apoptotic cell death in vitro and significant growth suppression in vivo. CONCLUSIONS: This study shows the therapeutic potential of SOX2 silencing for embryonal carcinoma. However, further improvements are needed in SOX2-siRNA delivery to the tumor.

[Self-catheterizable urinary re-diversion using the appendix for urethral recurrence after ileal neobladder].

A 68-year-old man underwent urinary re-diversion due to urethral recurrence 2 years after radical cystectomy with ileal neobladder reconstruction. Computed tomography, magnetic resonance imaging and cystoscopy revealed anastomotic recurrence between bladder and urethra with a tendency of urinary retention. Transurethral resection of bladder tumor was performed and pathological findings showed transitional cell carcinoma (TCC), papillary invasive G3, pT1 or more. Finally, we performed total urethrectomy and partial resection of bladder neck with self-catheterizable urinary rediversion using appendix. Pathological findings showed TCC, G3, pT1. Self-catheterizable urinary re-diversion using the appendix can be an option for urethral recurrence after ileal neobladder reconstruction.

[Ureteral cancer occurred in megaureter].

A 58-year-old man visited our hospital with a complaint of asymptomatic gross hematuria for three weeks. The urine cytology at another clinic had indicated Papanicolaou class V. A physical examination revealed soft abdominal distention in lower abdomen. Ultrasonography demonstrated an extremely dilated left pelvis, calyx and ureter in which a round mass was detected. Enhancement CT showed a mass 2 cm in diameter in the middle part of the dilated left ureter. These findings suggested the diagnosis of left ureteral cancer having developed in the megaureter. Neither VUR nor UVJ stenosis were identified by VCG and RP. MR-urography showed a severely dilated left pelvis and tortuous megaureter. On the diagnosis of left ureteral cancer left nephroureterectomy with cuff of bladder was performed. Gross findings showed a 2 cm sized papillary tumor in the extremely dilated ureter, and pathological findings showed grade 2, papillary transitional cell carcinoma and non-specific ureteritis in the dilated ureter. Postoperative course was non-eventful. Postoperative 3 months later multiple bladder tumors were detected all over the bladder, and so TUR-Bt and intravesical instillation therapy with pirarubisin was performed. However multiple bladder tumors had been relapsed and so finally radical cystectomy and right cutaneous ureterostomy were undergone postoperative 6 months later. He has been well 48 months postoperatively.

Left Adrenal Tumor Disappeared Outside a Field of Vision During Laparoscopic Surgery: The True Identity Was Gastrointestinal Stromal Tumor.

Background: We report a case of gastrointestinal stromal tumor (GIST) mimicking a left adrenal tumor. Case Presentation: A 62-year-old female was referred to our hospital for the treatment of left adrenal tumor of 2.8 × 2.3 cm incidentally found during her annual checkup. The preoperative diagnosis based on upper gastroscopy and imaging complete examinations was nonfunctional left adrenal tumor possessing malignant potential. Transperitoneal laparoscopic left adrenalectomy was performed. However, the tumor was not found in the excised adrenal gland that had been completely removed during surgery. Repeat computed tomography revealed the presence of the same tumor. Finally, reoperation led us to the true diagnosis of GIST. Conclusion: Many urologists are not familiar with GIST. It is necessary to take GIST into consideration when left adrenal tumor close to the stomach is diagnosed. We discuss the traps which we fell into during the perioperative period in this case.

[A prostatic duct carcinoma difficult to distinguish from transitional cell carcinoma: a case report].

A 77-year-old male with a complaint of dysuria and gross hematuria for 3 months visited our hospital. Abdominal ultrasonography, computed tomographic scan and magnetic resonance imaging revealed a prominent tumor from the bladder neck. Serum prostate specific antigen (PSA) level was high (1,130 ng/ml) suggesting prostate cancer, but transitional cell carcinoma (TCC) was detected by transurethral biopsy. Bone scintigraphy revealed multiple bone metastasis. Since gross hematuria requiring bladder tamponade continued, simple cystoprostatectomy and cutaneous ureterostomy were performed. Pathological findings showed prostatic acinar carcinoma and prostatic duct carcinoma mimicking TCC, and PSA immunohistochemically weak positive. The final diagnosis was prostate cancer consisting of acinar and ductal component. Adjuvant hormonal therapy was performed, but was ineffective. The patient died 2.5 months after operation. We reviewed and discussed 66 cases of prostatic duct carcinoma, including our case, in the Japanese literature.

[Fibrous pseudotumor of the tunica vaginalis testis: a case report].

A case of fibrous pseudotumor originating from the tunica vaginalis testis is reported. A 42-year-old man was referred to our hospital with the complaint of painless nodules along his right epididymis. There was no evidence of specific history. Ultrasonography showed an isoechoic small mass attached to the right testis. Inflammatory granulomas of the right epididymis were suspected, and an operation was carried out. The operative appearance indicated tumors of various sizes originating from the tunica vaginalis testis. Tumors were resected with the tunica vaginalis testis. Pathological diagnosis of the tumor was a fibrous pseudotumor. We reviewed and discussed 33 cases of intrascrotal fibrous pseudotumor, including our case, in the Japanese literature.

[A case of liposarcoma of the renal capsule].

A 58-year-old woman was referred to our institution for treatment of a left renal tumor revealed by follow-up computed tomography (CT) of a pancreatic tumor. The CT showed a heterogeneous, perirenal mass containing areas of fat density. Angiography showed no feeding artery. Left nephrectomy was performed and pathological examination revealed a well-differentiated liposarcoma of the renal capsule. At the third-month follow-up, the patient was completely asymptomatic and free of recurrence. Primary tumors of the renal capsule are uncommon and liposarcoma of the renal capsule is distinctly rare. There have been only 17 reports of liposarcoma arising from the renal capsule in Japan. We, herein, report a case of liposarcoma of the renal capsule.

[Two cases of renal cell carcinoma with ascites after interleukin-2 therapy].

One of the most common and problematic side effects of interleukin-2 therapy (IL-2) is vascular leak syndrome (VLS). VLS is characterized by an increase in vascular permeability accompanied by extravasation of fluids and proteins from the capillary vessels into the tissues resulting in interstitial edema, weight gain, pleural effusion, ascites in severe form, multiple organ failure. We, herein, report two cases of VLS, which occurred following IL-2 therapy against metastatic renal cell carcinoma. One of them died of multiple organ failure one month after the cessation of IL-2 therapy.

[A case of urinary and miliary tuberculosis detected during examination for renal failure].

A case of urinary and miliary tuberculosis in a 51-year-old male is reported. The patient with the complaint of low grade fever at night and appetite loss had visited another clinic. Laboratory data showed renal failure (serum creatinine 3.9 mg/dl, BUN 35.1 mg/dl) and he was referred to our hospital. Ultrasonography and computed tomography (CT) revealed bilateral hydronephrosis. Therefore we suspected postrenal renal failure. We performed cystoscopy in order to perform retrograde pyelography and to indwell double J stent. The bladder showed yellow-whitish nodules all over the bladder. Tuberculous bacilli were detected in the urine by smear, polymerase chain reaction (PCR) and culture. Chest radiography and CT revealed multiple granular nodules and so diagnosed miliary tuberculosis. Immediately combination chemotherapy of with isonicotinic acid hydrozide, rifapicin, ethanbutal and pirazinamide was administered. Histopathology by bladder biopsy showed epithelioid cell granuloma. Chemotherapy was effective, but the vesical capacity was contracted to less than 50 ml, and we suspect that the patient will need vesical augmentation.

A novel fully automated molecular diagnostic system (AMDS) for colorectal cancer mutation detection.

BACKGROUND: KRAS, BRAF and PIK3CA mutations are frequently observed in colorectal cancer (CRC). In particular, KRAS mutations are strong predictors for clinical outcomes of EGFR-targeted treatments such as cetuximab and panitumumab in metastatic colorectal cancer (mCRC). For mutation analysis, the current methods are time-consuming, and not readily available to all oncologists and pathologists. We have developed a novel, simple, sensitive and fully automated molecular diagnostic system (AMDS) for point of care testing (POCT). Here we report the results of a comparison study between AMDS and direct sequencing (DS) in the detection of KRAS, BRAF and PI3KCA somatic mutations. METHODOLOGY/PRINCIPAL FINDING: DNA was extracted from a slice of either frozen (n = 89) or formalin-fixed and paraffin-embedded (FFPE) CRC tissue (n = 70), and then used for mutation analysis by AMDS and DS. All mutations (n = 41 among frozen and 27 among FFPE samples) detected by DS were also successfully (100%) detected by the AMDS. However, 8 frozen and 6 FFPE samples detected as wild-type in the DS analysis were shown as mutants in the AMDS analysis. By cloning-sequencing assays, these discordant samples were confirmed as true mutants. One sample had simultaneous "hot spot" mutations of KRAS and PIK3CA, and cloning assay comfirmed that E542K and E545K were not on the same allele. Genotyping call rates for DS were 100.0% (89/89) and 74.3% (52/70) in frozen and FFPE samples, respectively, for the first attempt; whereas that of AMDS was 100.0% for both sample sets. For automated DNA extraction and mutation detection by AMDS, frozen tissues (n = 41) were successfully detected all mutations within 70 minutes. CONCLUSIONS/SIGNIFICANCE: AMDS has superior sensitivity and accuracy over DS, and is much easier to execute than conventional labor intensive manual mutation analysis. AMDS has great potential for POCT equipment for mutation analysis.

DNMT3L is a novel marker and is essential for the growth of human embryonal carcinoma.

PURPOSE: Testicular germ cell tumors (TGCT) have a unique epigenetic profile distinct from that of other types of cancer. Elucidation of these properties has a potential to identify novel markers for TGCTs. EXPERIMENTAL DESIGN: We conducted comprehensive analysis of DNA methyltransferase (DNMT) gene expression in TGCTs. Based on the expression profiles of DNMT genes in TGCTs, we generated a rabbit polyclonal anti-human DNMT3L antibody. We then studied the role of DNMT3L in TGCTs by the treatment of two embryonal carcinoma (EC) cell lines with a small interfering RNA system. Finally, we evaluated the immunohistochemical detection of DNMT3L in TGCT tissues. We also compared the patterns of DNMT3L immunohistochemistry with those of CD30 and SOX2. RESULTS: Among the DNMT genes, we found that mRNA for DNMT3L was specifically expressed in TGCTs, but neither in normal testicular tissues nor in cancer cells of somatic tissue origin. DNMT3L protein was strongly expressed in two EC cell lines, but not in the cell lines of somatic tissue origin. Transfection of small interfering RNA for DNMT3L significantly reduced DNMT3L expression and resulted in growth suppression and apoptosis in EC cells. Immunohistochemical analysis showed that DNMT3L protein was present only in EC cells, but not in the other types of TGCT components and cancer cells of somatic tissue origin. DNMT3L staining was more prominent and specific than CD30 or SOX2 staining for detecting EC cells. CONCLUSION: DNMT3L is a novel marker and is essential for the growth of human embryonal carcinoma.

Primary heterologous carcinosarcoma of the ureter with necrotic malignant polyps. Report of a case and review of the literature.

Carcinosarcoma is a rare and aggressive disease characterized by biphasic neoplasms with distinct mesenchymal and epithelial components. We report a case of ureteral carcinosarcoma with malignant necrotic polyps. The patient was a 58-year-old woman with painless hematuria, who was later diagnosed as having ureteral carcinosarcoma. Three long pendulous polypoid-shape tumors consisting of high-grade transitional cell carcinoma with chondrosarcomatous and osteosarcomatous elements were found. Two months after nephroureterectomy, the tumor relapsed in the bladder. Despite anterior exenteration, the patient died of local recurrence 6 months after her initial visit. To our knowledge, only 10 cases of this disease have been reported in the literature.

Mixed tumor of paratesticular rhabdomyosarcoma and an adenomatoid tumor in an elderly patient.

We report a case of a mixed tumor of paratesticular rhabdomyosarcoma and an adenomatoid tumor in an elderly patient. Rhabdomyosarcoma is one of the most common childhood tumors; however, it rarely occurs in the elderly. In addition, to our knowledge, paratesticular rhabdomyosarcoma and adenomatoid tumor rarely form mixed tumors. Finally, we consider the pathogenesis of diploblastic tumors.