Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder.

PURPOSE: Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. METHODS: We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). CONCLUSIONS: Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

Resection of bulky chromophobe renal cell carcinoma resolved severe idiopathic thrombocytopenic purpura: A case report.

Idiopathic thrombocytopenic purpura associated with renal cell carcinoma is relatively rare. We report the case of a 48-year-old woman with massive renal cell carcinoma, measuring approximately 20 × 14 × 14 cm, who presented with severe thrombocytopenia: platelet count, 2000 cells/µL. After confirming normal bone marrow, she received high-dose dexamethasone and intravenous gamma globulin, which raised the platelet count to normal levels. She then underwent left radical nephrectomy. The pathological examination showed chromophobe renal cell carcinoma. After the resection, the platelet count was maintained within the normal range without any treatment. The current case is the first report of chromophobe renal cell carcinoma causative of severe idiopathic thrombocytopenic purpura.

Contracted bladder developing after prostate brachytherapy.

This report describes an extremely rare case of severely contracted bladder developing after prostate brachytherapy. In April 2001, a 76-year-old man initially presented to our hospital for weak urinary stream. The patient was diagnosed with and treated for benign prostatic hyperplasia. During follow up, prostate-specific antigen level was elevated. In November 2005, the patient underwent transrectal prostate biopsy. Pathology showed adenocarcinoma, Gleason score 3 + 4 = 7. The patient was diagnosed with stage cT1cN0M0 prostate cancer. In January 2006, he underwent brachytherapy for prostate cancer. The procedure of brachytherapy was uneventful and the patient was discharged without any problems. Four months after the implant, the patient was admitted to our hospital for deterioration of kidney function as a result of a contracted bladder. Urinary culture of tuberculosis was negative and urinary cytology was class II. A urethral catheter was indwelled and the patient has been followed every month for catheter replacement. Bladder capacity is now less than 5 mL.

[Primary carcinoma of the female urethra: report of 4 cases].

We experienced 4 cases of primary carcinoma of the female urethra during 1998 to 2011. All of the cases were diagnosed primary urethral cancer according to tumor biopsy, cystoscopy, and computed tomography (CT) or magnetic resonance imaging (MRI). Patients were between 66 to 92 years of age at the time of presentation. Presenting symptoms included gross hematuria in 1 case, urinary retention in another case, and vulvar bleeding in 2 cases. Pathology showed urothelial carcinoma in 2 cases, adenocarcinoma in 1 case, and squamous cell carcinoma in another case. There were 2 patients with stage D, 1 patient with C, and another with B. Three patients were treated with total cystectomy and ileal conduit. One patient was treated with radiation. Two patients died from urethral cancer, 1 patient is free from disease for 12 months, and another patient became lost during follow-up.

[Predictors of operative blood loss in patients undergoing small incision radical prostatectomy].

We performed 82 cases of small incision radical prostatectomy from July, 2003 to September, 2009. There were 38 cases of cT1c, 41 cases of cT2, and 3 cases of cT3. Mean operative time was 222 +/- 31.7 (min.). Mean operative blood loss was 1,232 +/- 583 (ml). We evaluated factors predicting operative blood loss, such as prostate volume, body mass index (BMI), age, and preoperative PSA level. Group with smaller prostate volume and group with lower BMI showed significantly less blood loss compared to that of a higher group (p = 0.0009, p = 0.0014, respectively). Multivariate analysis showed that prostate volume and BMI were significant predictors for operative blood loss (p = 0.0005, p = 0.0122, respectively). Prostate volume and BMI may be a useful predictor for operative blood loss.

Swelling of the prostate gland by permanent brachytherapy may affect seed migration.

OBJECTIVE: The purpose was to monitor implanted seeds and to determine factors contributing to seed migration after permanent prostate brachytherapy. METHODS: Sixty-two consecutive patients with Stage 1 prostate cancer who underwent brachytherapy with (125)I seeds between February 2008 and May 2009 were studied prospectively. On post-operative days 1, 7 and 30, scintigraphy was added to conventional radiography to monitor the migration of the implanted seeds. The prostate volume was measured during the pre-planning stage using ultrasound and during the post-planning stage using computed tomography on post-operative days 0 and 30. Magnetic resonance imaging was performed on day 30. RESULTS: Of the 4843 seeds implanted in the prostates of 62 patients, 108 seeds (2.2%) in 43 patients (69.4%) exhibited seed migration. Thirty-five seeds could not be identified using any of the imaging modalities and were likely passed during urination (0.7% of the total number of seeds). The maximum number of migrated seeds in one patient was 10 of the 85 implanted seeds. The fraction of patients with seed migration or loss increased from 27.4% on day 1 to 69.4% on day 30. The number of seeds that had migrated from the prostate increased from 48 (0.1% of the total number of seeds) on 1 day to 78 (1.0%) on day 7 and 108 (2.2%) on day 30. Of the seeds lost from the prostate, 38.9% embolized to the lungs. The seed loss during the first post-operative month was closely correlated with the swelling of the prostate gland between the pre-planning measurement and the post-planning measurement performed on day 0 (P < 0.0001). CONCLUSIONS: Prostate swelling between the pre-planning and post-planning (day 0) measurements was significantly associated with seed migration, and adequate attention should be given to this issue.

Primary aldosteronism associated with severe rhabdomyolysis due to profound hypokalemia.

A 55-year-old Japanese man was admitted to our hospital with severe weakness. Without measurement of serum electrolyte concentrations, diuretic therapy for hypertension was started 2 weeks prior to admission. Laboratory findings showed profound hypokalemia (1.4 mEq/L), and extreme elevation of the serum creatinine phosphokinase levels (15,760 IU/L), suggesting that the patient had hypokalemic paralysis and hypokalemia-induced rhabdomyolysis. Further evaluations, including adrenal venous sampling strongly suggested that he had primary aldosteronism. He was treated successfully by laparoscopic adrenalectomy. This case provides an important lesson that serum electrolyte concentrations should be measured in hypertensive patients before the administration of antihypertensive agents.

Factors associated with variation in utility scores among patients with prostate cancer.

OBJECTIVE: We aimed to assess the effects of age, comorbidity, and disease-specific functions on utility scores derived from three methods on prostate cancer. METHODS: A total of 330 Japanese prostate cancer patients were asked to answer self-administered questionnaires. Community-weighted utility scores were derived from the EuroQoL-5D (EQ-5D) and the Short Form-36 (SF-36), while the patient's directly elicited utility score was derived from time trade-off technique. Univariate and multivariate analyses were performed to examine the relation between covariates and utility scores. We assigned age, the Index of Co-existent Disease, and disease-specific functions including sexual, urinary, bowel, and hormonal function as covariates. RESULTS: Bowel and hormonal function were related to utility scores, while age and sexual function were not. Comorbidities were more closely related to utility scores derived from EQ-5D and SF-36. CONCLUSIONS: These results contribute to an understanding of which factor has an impact on utility scores in patients with prostate cancer.

Scintigraphic detection of 125I seeds after permanent brachytherapy for prostate cancer.

UNLABELLED: The purpose of this investigation was to monitor the localization and migration of 125I seeds after permanent brachytherapy for prostate cancer using a new scintigraphic technique that may overcome the drawbacks of conventional x-ray methods. METHODS: 125I seeds emit gamma-rays with an average energy peak of 28 keV. We used a gamma-camera equipped with low-energy high-resolution collimators that were tuned to an energy level of 35 keV with a 70% window width. Sixteen patients with prostate cancer were examined after 125I seed insertion. The number of seeds remaining in the prostate was confirmed using pelvic CT for postoperative dose planning; however, seeds that had migrated outside the prostate could not be detected. Furthermore, the migrated seeds were not completely traceable using chest or abdominal radiography. Thus, we adopted a scintigraphic technique to perform this task. The evaluation of radiography and scintigraphy findings was masked, and the rates of migrated seed detection were statistically examined using the McNemar test. To localize the migrated seeds, we fused the scintigraphic images of the migrated seeds and the patients' contours. RESULTS: Scintigraphy was successfully used to detect 20 migrated seeds of a total of 1,182 implanted seeds, whereas radiography was successfully used to detect 7. The sensitivity of the scintigraphy results was 20 of 20 (100%), whereas that of the radiography results was 7 of 20 (35%). Seed migration was detected in 11 of 16 patients (69%) using scintigraphy, whereas seed migration was detected in only 4 patients (25%) using radiography; this difference was statistically significant (P = 0.016). CONCLUSION: Scintigraphy is more effective for detecting seed migration and monitoring the localization of 125I seeds than radiography. The precise anatomic location of migrated seeds can be pinpointed using fusion images. Scintigraphy may become a standard procedure for monitoring seed migration during 125I brachytherapy in patients with prostate cancer.

Decision analyses in consideration of treatment strategies for patients with biochemical failure after curative therapy on clinically localized prostate cancer in the prostate-specific antigen era.

BACKGROUND: The introduction of prostate-specific antigen (PSA) testing has not only shortened the time required to make diagnosis but changed the treatment strategies of localized prostate cancer. We conducted the decision analysis on its treatment focusing on patients with biochemical failure. METHODS: We developed a Markov model to calculate life expectancy (LE) and quality-adjusted life expectancy (QALE) stratified by age, comorbidity and tumor characteristics in patients with newly diagnosed prostate cancer or biochemical failure after curative therapy. For newly diagnosed patients, three treatment strategies were considered as primary managements: radial prostatectomy (RP), external beam radiotherapy (EBRT) and watchful waiting (WW). Managements considered for biochemical failure were: after RP, salvage radiotherapy (SRT), salvage hormonal therapy (SHT) and WW; and after EBRT, SHT and WW. Transition probabilities in the Markov model were derived from published studies. Quality of life (QOL) data to estimate QALE score were derived from 323 patients with prostate cancer. RESULTS: For patients with Gleason 2-6 cancer at diagnosis, WW yielded the greatest number of QALE. For patients with Gleason 7 cancer, it was controversial whether curative therapy was the preferred strategy. For patients with Gleason 8-10 cancer, curative therapy yielded the greatest number of QALE in younger patients without severe comorbidity. Patients' benefit from salvage therapy for biochemical failure after curative therapy depended on age, comorbidities, tumor characteristics and QOL effect. CONCLUSIONS: Our findings support the need for various treatment options, taking into consideration the patient's age, comorbidity and the QOL effect in the aging society.

Novel germline mutations in the SDHB and SDHD genes in Japanese pheochromocytomas.

The SDHA, SDHB, SDHC, and SDHD genes code for subunits of succinate dehydrogenase (SDH), which forms part of the mitochondrial respiratory chain. Germline mutations in the genes encoding SDHB and SDHD have been reported in familial paragangliomas/pheochromocytomas and in apparently sporadic pheochromocytomas. SDHB and SDHD mutations are widely distributed along the genes with no apparent hot spots. SDHB mutations are often detected in malignant and extra-adrenal pheochromocytomas. SDHD mutations are also detected frequently in head and neck paragangliomas. We sequenced the entire coding regions of the SDHB and SDHD genes in 17 pheochromocytomas. We identified novel heterozygous G to A point mutations at the first base of intron 3 of the SDHB gene in a malignant extra-adrenal abdominal pheochromocytoma patient, and at the first base of codon 111 of the SDHD gene in an adrenal pheochromocytoma patient. Further, we confirmed the SDHD mutation by DHPLC. The prevalence of SDHB and SDHD mutations in pheochromocytomas we examined was 12% (2/17). Thus, we identified two novel SDH mutations in Japanese pheochromocytomas. Further studies will investigate the oncogenic potential of these mutations.

Acute pericarditis as a result of unusual metastasis of the visceral pleura in a patient with testicular seminoma.

A 30-year-old man with a left testicular swelling was referred to our hospital. We performed a left high orchiectomy based on a diagnosis of clinical stage II testicular cancer. Pathological specimens of the left testis showed seminoma. The patient underwent three courses of combined chemotherapy. The retroperitoneal lymph nodes were dissected and there were no viable cancer cells. Twelve years later a right testicular tumor was discovered. The patient underwent a right high orchiectomy. Pathological specimens of the testis showed seminoma, and the patient was treated with prophylactic irradiation. One year after discharge a metastasis was found at a left supraclavicular fossa. The patient was treated with combined chemotherapy and irradiation. Six months after the treatment he complained of dyspnea. We diagnosed the condition as pleuritis carcimatosa. Two days after irradiation to the left thorax the patient suffered a sudden and fatal cardiac arrest. Autopsy survey revealed pericarditis as a result of a direct invasion of visceral pleural metastasis.

Hemiresective reconstruction of a redundant ileal conduit with severe bilateral ileal conduit-ureteral re fl ux.

A 58-year-old man was referred to our hospital with high fever and anuria. Since undergoing a total pelvic exenteration due to bladder-invasive sigmoid colon cancer, urinary tract infections had frequently occurred. We treated with the construction of a bilateral percutaneous nephrostomy (PCN), and chemotherapy. Although we replaced the PCN with a single J ureteral catheter after an improvement of infection, urinary infection recurred because of an obstruction of the catheter. Urological examinations showed that an ileal conduit-ureteral reflux caused by kinking of the ileal loop was the reason why frequent pyelonephritis occurred. We decided to resect the proximal segment to improve conduit-ureteral reflux for the resistant pyelonephritis. After the surgery, the excretory urogram showed improvement and the urinary retention at the ileal conduit disappeared. Three years after the operation, renal function has been stable without episodes of pyelonephritis. Here we report a case of open repair surgery of an ileal conduit in a patient with severe urinary infection.

Different transformation of mature teratoma in a patient with mixed germ cell tumor of the testis.

A 44-year-old male was referred with a left supraclavicular lymphadenopathy. A biopsy of the lymph node showed metastatic embryonal carcinoma. Tumor markers were present at high levels: alpha-fetoprotein 253.9 ng/mL, beta-human chorionic gonadotrophin 62 ng/mL. Computed tomography (CT) showed retroperitoneal adenopathy. High orchiectomy was done. The patient was treated with three cycles of etoposide plus cisplatin, achieved normalization of the serum tumor markers and underwent retroperitoneal lymph node dissection. Pathological findings of multiple lymph nodes showed teratomatous glands without viable cells. At follow-ups performed every 3 months, tumor markers remained within normal limits and no evidence of recurrence was observed. Eight years after first admission a CT scan revealed a cystic tumor 1 cm in diameter in the para-aortic region. The cystic tumor continued to slowly grow, expanding by 1 cm in diameter per year without elevation of tumor markers. The para-aortic tumor had grown to 4 cm in diameter and a left supraclavicular lymphadennopathy recurred. A resection of the supraclavicular cystic tumor showed mucinous cystadenocarcinoma, but a cystic tumor in the para-aortic region revealed mature teratoma. Here we report a case of mature teratoma with metastases at supraclavicular and para-aortic lymph nodes which had different transformations in spite of both regions consisting of cystic tumors.

Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.

We report on the clinical and molecular findings in 25 males and three females with Kallmann syndrome (KS) aged 10-53 yr. Ten males were from five families, and the remaining 15 males and three females were apparently sporadic cases. Molecular studies were performed for Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, also known as KAL2) by sequence analysis for all the coding exons, by PCR-based deletion analysis, and by fluorescence in situ hybridization (FISH) analysis, showing six novel and two recurrent intragenic KAL1 mutations in seven familial and four sporadic male cases and two novel intragenic FGFR1 mutations in two sporadic male cases. In addition, submicroscopic deletions at Xp22.3 involving VCX-A, STS, KAL1, and OA1 were identified in three familial cases and one sporadic male case affected by a contiguous gene syndrome. Clinical assessment in the 15 males with KAL1 mutations showed normal and borderline olfactory function in two males and right-side dominant renal lesion in seven males, in addition to variable degrees of hypogonadotropic hypogonadism (HH) in all the 15 males and olfactory dysfunction in 13 males. The two males with FGFR1 mutations had HH and anosmia and lacked other features. Clinical features in the remaining 11 cases with no demonstrable KAL1 or FGFR1 mutations included right renal aplasia in one female, cleft palate in one male, cleft palate and perceptive deafness in one male, and dental agenesis and perceptive deafness in one male, in addition to a variable extent of HH and olfactory dysfunction. The results suggest the following: 1) KAL1 mutations might be more prevalent in the Japanese patients than previously estimated in the Caucasian patients and can be associated with apparently normal olfactory function; 2) FGFR1 mutations account for approximately 10% of KS patients, as previously reported in the Caucasian patients, and can result in HH and olfactory dysfunction-only phenotype; and 3) renal aplasia, which is characteristic of KAL1 mutations, and cleft palate and dental agenesis, which are characteristic of FGFR1 mutations, can occur in patients without KAL1 and FGFR1 mutations.

Tiny nodule in the testicle: case report of a sertoli cell tumor.

Sex cord-stromal tumors of the testis are rare. We report on a small Sertoli cell tumor in the testicle. According to published reports, a nodular lesion on the testicle has a variety of differential diagnoses. Preoperatively, it is very difficult to differentiate between a tumorous lesion and an inflammatory change. When a tiny nodule in the testicle is encountered, we propose limited, testicular-sparing surgery according to the frozen section diagnosis.

Computed tomography-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenoma.

We reported the outcomes of computed tomography (CT)-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenomas. With the patient in a prone position, the puncture needle was inserted vertically downward into the adenoma with frequent CT scanning. After confirmation by pilot injection with contrast medium, a small aliquot of 40-50% acetic acid was injected and repeated. Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one session of ethanol injection, were performed on 10 patients (five patients with primary aldosteronism and five patients with Cushing's or subclinical Cushing's syndrome) without any complications except transient upper abdominal pain during the acetic acid injection. The follow-up period ranged from 5-69 months. The treatment resulted in almost an extirpation of the adrenocortical hyperfunction in seven patients after one or two sessions. CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adrenocortical adenomas.