Analysis of the relationship between prescribed dose and dosimetric advantage of real-time intraoperatively built custom-linked seeds in iodine-125 prostate brachytherapy.

BACKGROUND: The purpose of this study was to investigate the differences in the dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds between permanent iodine-125 (I-125) seed implantation (PI) alone and PI followed by external-beam radiation therapy (EBRT) for prostate cancer. METHODS: We reviewed the records of 62 patients with localized prostate cancer who received transperineal interstitial brachytherapy with I-125 using free seeds or IBCL seeds. Twenty-four low- and intermediate-risk patients underwent PI alone with the prescribed dose of 160 Gy, and 39 high-risk patients underwent PI with 110 Gy, followed by EBRT with 45 Gy (PI + EBRT). Intraoperative and post-implant dosimetric parameters 1 month after implantation were collected and analyzed. RESULTS: The numbers of patients implanted with free seeds and IBCL seeds were 14 (58.3%) and 10 (41.7%), respectively, in the PI group and 25 (65.8%) and 13 (34.2%), respectively, in the PI + EBRT group. In the PI group, although there were significant differences in prostate V100 (p = 0.003) and D90 (p = 0.009) and rectum V100 (p = 0.026) on intraoperative dosimetry, these differences were not found on post-implant dosimetry. In the PI + EBRT group, the dosimetric parameters of IBCL seeds, such as prostate V200 (p = 0.013) and V250 (p = 0.010) and urethra D30 (p = 0.038), were better than those of free seeds on intraoperative dosimetry. Furthermore, even on post-implant dosimetry, prostate D90 (p = 0.004), V150 (p = 0.001), and homogeneity index (HI, p = 0.001), as well as V200 (p = 0.001) and V250 (p = 0.020), and urethra D5 (p = 0.008) as well as D30 (p = 0.003) had a better dosimetric quality in IBCL seeds than in free seeds. There was no significant difference in the operation time between free seeds and IBCL seeds in each PI and PI + EBRT group. CONCLUSIONS: Our results reveal that greater dosimetric benefits could be obtained using IBCL seeds in the case of permanent implantation with a lower prescribed dose, such as PI + EBRT, rather than PI alone.

The retrospective analysis of the relationship between prescribed dose and risk factor for seed migration in iodine-125 prostate brachytherapy.

PURPOSE: The aim was to determine the dose-specific incidence and predictors of seed loss/migration after permanent seed implantation (PI) for localized prostate cancer. MATERIALS AND METHODS: The records of 79 patients with T1c-T3a prostate cancer who underwent prostate brachytherapy with loose iodine-125 seeds were retrospectively reviewed. Of these patients, 33 with low or intermediate risk underwent PI with the prescribed dose of 160 Gy for the clinical target volume (CTV), and 46 with high risk underwent PI with 110 Gy for the CTV followed by external beam radiotherapy (EBRT) with 45 Gy. Each CTV was defined as a contoured prostate. After PI, the incidence of seed loss/migration was assessed by a series of radiographs. RESULTS: Seed migration occurred in 22 (0.479 %) of 4589 implanted seeds 1 month after implantation. In PI alone, the number of needles (P = 0.081) and the number of seeds (P = 0.071) showed a trend for a difference between those with and without seed loss. In PI + EBRT, there was a significant difference in the discrepancy between the seed numbers calculated by the nomogram and actually implanted (P = 0.032). CONCLUSIONS: It is suggested that the discrepancy in seed numbers might be the predictor for seed migration in PI with 110 Gy.

[Successful control of hyper-cortisolemia due to ACTH-producing thyroid carcinoid by laparoscopic bilateral adrenalectomy : a case report].

A 22-year-old man was referred to our hospital because of facial edema and increasing body weight. Under the diagnosis of Cushing syndrome due to an adrenocorticotropic (ACTH)-producing thyroid tumor, thyroidectomy with regional lymph node dissection was performed. Histopathological diagnosis was thyroid carcinoid. In spite of the operation, serum ACTH and cortisol concentrations increased again due to mediastinal lymph node metastasis. His hyper-cortisolemia was resistant to drug therapy. Then, laparoscopic bilateral adrenalectomy was performed. After the operation, hyper-cortisolemia and clinical symptoms markedly improved. An additional chemotherapy is implemented because of new metastasis in the mediastinum lymph nodes.

[Local recurrence of pheochromocytoma associated with von Hippel-Lindau disease 26 years after bilateral adrenalectomy : a case report].

A 60-year-old man who had undergone left adrenalectomy and right partial adrenalectomy for bilateral pheochromocytoma 26 years ago was found to have an elevated serum noradrenaline (NA) and dopamine (DA) during a long-term follow-up. At the time of right partial adrenalectomy, the normal part of the right adrenal gland was preserved. His cousin and second cousin had pheochromocytoma associated with von Hippel-Lindau (VHL) disease. His eldest daughter had cerebellar hemangioblastoma. Computed tomography and magnetic resonance imaging revealed a tumor which was 17 mm in diameter with contrast enhancement in the vicinity of the S6 region in the liver. 123 I-metaiodobenzylguanidine (MIBG) scintigraphy showed an abnormal accumulation in the same area. The tumor was surgically removed under the diagnosis of recurrence of pheochromocytoma. Histopathological examination revealed findings consistent with recurrent pheochromocytoma. After operation, serum NA and DA returned to normal range and the abnormal up-take on 123I-MIBG scintigraphy disappeared. Genetic testing revealed that the patient and his daughter had VHL disease. An extensive genetic examination and long-term follow-up should be considered for the present family.

[Testicular tumor arising in intra-abdominal testis which was not detected at prior orchidopexy : a case report].

A 35-year-old man with an intra-abdominal testicular tumor arising from the right unresolved intraabdominal testis is reported. At 10 years old, left orchidopexy was successfully performed for bilateral undescended testes. However, the right testis was not detected during the operation, and it was diagnosed as vanishing testis. Twenty-five years later, he was referred to our hospital with the complaint of right lower abdominal pain. Computed tomography revealed huge pelvic tumors and bulky para-aortic lymph node swellings. Histopathologic examination of the needle biopsy specimen obtained from the pelvic tumor revealed seminomatous germ cell tumor. Taking the results with a tumor marker study into consideration, the patient was tentatively diagnosed with non-seminomatous germ cell tumor NSGCT (stage IIB) arising from the unresolved intra-abdominal testis or extragonadal germ cell tumor. He received 3 courses of bleomycin, etoposide, cisplatin (BEP), and 4 courses of VP-16, ifosfamide, cisplatin (VIP). After chemotherapy, we performed tumorectomy and retroperitoneal lymphadenectomy because tumor markers were normalized and 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)-CT revealed normalization. We identified the pelvic tumor as an intra-abdominal testicular tumor arising from right unresolved intra-abdominal testis. Pathological examination revealed no residual tumor cells. There has been no recurrence 17 months after surgery.

[Adult mature teratoma of the testis: a case report].

A 33-year-old man visited our hospital complaining of painless left scrotal swelling. Serum alphafetoprotein (AFP) and human chorionic gonadotropin-beta (HCG-ß) were within normal range. Computed tomography revealed a heterogeneous tumor in the left scrotum and para-aortic lymph node swelling. We diagnosed the tumor as stage IIA testicular cancer and performed left high inguinal orchiectomy. Histopathological diagnosis was mature teratoma with no associated malignant germ cell tumor. The patient was followed-up without adjuvant chemotherapy because the size of para-aortic lymph nodes was remarkably reduced one month after the orchiectomy. The patient must be followed up carefully for possible metastasis.

Blood group antigen-targeting peptide suppresses anti-blood group antibody binding to antigen in renal glomerular capillaries after ABO-incompatible blood reperfusion.

BACKGROUND: Antibody-mediated rejection after ABO-incompatible kidney transplantation (ABO-I KTx) is a major barrier to transplantation success. The advent of immunosuppressive therapy has markedly improved graft survival in ABO-I KTx. However, compared with normal KTx, clinical conditions during ABO-I KTx are difficult to control because of overimmunosuppression. To reduce the need for immunosuppression, we aimed to develop a novel blood group antigen-neutralizing therapy. METHODS: We screened for an ABO blood group antigen-targeting peptide (BATP) by screening of T7 phage-displayed peptide library. After screening, hemagglutination inhibition assays, enzyme-linked immunosorbent assay, and cytotoxicity assay were used to analyze the blood group antigen-blocking effect and toxicity of BATP. We also tested the inhibitory effects on anti-blood group antibody binding in normal human kidney tissues blocked with BATP and excised kidneys perfused ex vivo with BATP. RESULTS: We identified six peptide sequences that efficiently suppressed hemagglutination of red blood cells by anti-ABO blood group antibodies and binding of these antibodies to ABO histo-blood group antigens in kidney tissues. Surprisingly, ex vivo perfusion of BATP in kidneys excised from renal cell carcinoma patients caused significant suppression of anti-blood group antibody binding to antigen and IgG and IgM deposition in renal glomerular capillaries after ABO-I blood reperfusion. CONCLUSIONS: These data indicate that A/B blood group antigens on red blood cells and in kidney tissues may be neutralized by BATP. This approach may enable the development of a novel blood group antigen-neutralizing therapy to overcome the challenges of ABO-I KTx.

Carboplatin-gemcitabine combination chemotherapy upregulates AKR1B10 expression in bladder cancer.

BACKGROUND: AKR1B10 is considered to contribute to cell proliferation and chemoresistance. In the present study, we examined whether AKR1B10 expression is associated with disease-free survival in bladder cancer patients. METHODS: We obtained bladder cancer specimens from 10 patients before and after chemotherapy and measured AKR1B10 mRNA levels using real-time PCR. In addition, we conducted an immunohistochemical examination of AKR1B10 expression in 57 patients with bladder cancer before and after chemotherapy. RESULTS: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy group than in the pre-chemotherapy group (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared with the significantly higher score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001). The disease-free survival rate of post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(-) patients (100%) (log-rank test, p = 0.039). CONCLUSIONS: Although the present study is small and preliminary, our data suggest that post-chemotherapy AKR1B10 expression may be associated with a poor prognosis in patients who received carboplatin-gemcitabine combination chemotherapy and underwent cystectomy. Further study is warranted to elucidate its clinical significance.

Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study.

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer (BC) has better survival benefit than radical cystectomy (RC) alone. However, optimal dosing schedule, including drug selection, number of cycles, and interval between chemotherapy and cystectomy, as well as acceptable regimens remain to be established. We conducted a single-arm prospective study to evaluate efficacy and safety of neoadjuvant gemcitabine plus carboplatin (GCarbo) chemotherapy followed by immediate RC in patients with muscle-invasive BC, including cisplatin-unfit patients. METHODS: Between March 2005 and June 2011, we enrolled 116 patients with histologically proven muscle-invasive BC, including 44 % of the patients who were identified as cisplatin-unfit. All participants received two courses of GCarbo therapy, gemcitabine 800 mg/m(2) administered on days 1, 8, and 15 and carboplatin with an area under the curve of four (AUC 4) administered on day 2. RC and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. The primary endpoint was pT0 in the cystectomy specimen. Secondary endpoints were overall response rate, overall (OS) and disease-free survival (DFS), and toxicity. Survival after cystectomy was analyzed using the Kaplan-Meier method. RESULTS: The RC specimens of 28 (24.1 %) patients showed pT0. At a median follow-up period of 41 months, the OS and DFS rates were 89.7 and 86.3 %, respectively. No patients had grade 3/4 gastrointestinal toxicity or renal impairment. CONCLUSIONS: Neoadjuvant GCarbo therapy followed by immediate RC is safe, even in cisplatin-unfit patients, and provides a favorable pathological cancer-free state. The single-arm single-institution study design and relatively short observation period were limitations of this study.

[Metastatic renal tumor from oral floor cancer: a case report].

A 61-year-old man with oral floor cancer (adenoid cystic carcinoma, T2N0M1) was treated with systemicc hemotherapy and radiation therapy at the department of dentistry and oral surgery in our hospital. He had three lung metastases and renal tumors detected by screening computed tomography. The oral floor cancer responded to the treatment to achieve partial response. However, lung and renal metastases did not respond to chemotherapy. Then, the patient was referred to our clinic to rule out the possibility of lung metastasis from renal cell carcinoma. Laparoscopic left nephrectomy was performed and pathological examination on the renal lesions revealed adenoid cystic carcinoma, which had identical histopathological features to the oral floor cancer. To our knowledge, this is the first report of metastatic renal tumor from oral floor cancer (adenoid cystic carcinoma).

Sarcoidosis of the ureter.

We report a rare case of sarcoidosis of the ureter in a 65-year-old Japanese man. Left nephroureterectomy and regional lymph node dissection were performed under the clinical diagnosis of transitional cell carcinoma of the left ureter with lymph node metastasis. Microscopically, noncaseous epithelioid granuloma with large Langerhans cells was noted in the ureter and dissected lymph nodes. Pulmonary lesions were not found on computed tomography. The final diagnosis was sarcoidosis of the ureter. Although sarcoidosis is rare in the genitourinary tract, it should be considered in the differential diagnosis of urologic conditions.

[Adrenal pheochromocytoma with multiple neurofibromatosis on the trunk].

We report a case of adrenal pheochromocytoma in a patient with neurofibromatosis type 1 (NF1). A 65-year-old female patient was admitted to our hospital for examination of a right adrenal mass. The adrenal tumor was incidentally discovered by abdominal computed tomography during examination for hypertension in another hospital. She had large multiple neurofibromatous lesions and café-au-lait spots on the trunk. We thought that it was difficult to make a skin incision on normal skin. Serum and urinary catecholamines were markedly increased. Magnetic resonance imaging revealed a solid round tumor 3 cm in diameter, located in the right adrenal gland. Laparoscopic right adrenalectomy was performed. Serum and urinary catecholamines returned to the normal range on post-operative day 10. Laparoscopic surgery may be a good option for NF1 patients with pheochromocytoma, especially those who had multiple neurofibromatosis on the trunk.

Efficacy of SMART Stent Placement for Salvage Angioplasty in Hemodialysis Patients with Recurrent Vascular Access Stenosis.

Vascular access stenosis is a major complication in hemodialysis patients. We prospectively observed 50 patients in whom 50 nitinol shape-memory alloy-recoverable technology (SMART) stents were used as salvage therapy for recurrent peripheral venous stenosis. Twenty-five stents each were deployed in native arteriovenous fistula (AVF) and synthetic arteriovenous polyurethane graft (AVG) cases. Vascular access patency rates were calculated by Kaplan-Meier analysis. The primary patency rates in AVF versus AVG at 3, 6, and 12 months were 80.3% versus 75.6%, 64.9% versus 28.3%, and 32.3% versus 18.9%, respectively. The secondary patency rates in AVF versus AVG at 3, 6, and 12 months were 88.5% versus 75.5%, 82.6% versus 61.8%, and 74.4% versus 61.8%, respectively. Although there were no statistically significant difference in patency between AVF and AVG, AVG showed poor tendency in primary and secondary patency. The usefulness of SMART stents was limited in a short period of time in hemodialysis patients with recurrent vascular access stenosis.

[Additional effect of propiverine for naftopidil-resistant nocturia in the patient with benign prostate hypertrophy].

The efficacy and safety of additional administration of propiverine were prospectively studied for naftopidil-resistant nocturia in patients with benign prostatic hypertrophy (BPH). Patients of 50 years and over with BPH who experienced nocturia twice a night or more and an overall International Prostate Symptom Score (IPSS) of 8 or more were first administered naftopidil (50 or 75 mg/day) for 4 weeks. Thirty subjects who did not show improvement in nocturia and requested further treatment were enrolled in the present study. Propiverine was then administered concomitantly 10 mg/day for 8 weeks. Significant improvement was observed with additional propiverine in the frequency of nocturia on voiding diary, total IPSS, voiding symptom, storage symptom and nocturnal voiding scores. No significant change was observed in the peak urinary flow rate (Qmax), mean urinary flow rate (Qave), voided urine volume, or residual urine volume. Adverse events were dysuria (2 cases), increased residual urine (6 cases), weak urine flow (1 case), thirsty (2 cases), angular cheilitis (1 case). Administration of propiverine was suspended in 7 subjects, 1 following dysuria and 6 following increased residual urine volume. The suspension of propiverine following increased residual urine volume was significantly more prevalent in subjects with pretreatment Qmax values of less than 10 ml/second or in subjects whose prostate specific antigen (PSA) levels were 2 ng/ml or more. In conclusion, the results indicate that additional administration of propiverine may be useful for the patients with BPH who have naftopidil-resistant nocturia. However, caution must be exercised regarding Qmax and PSA levels.

[Ganglioneuroma with calcification mimicking adrenal tumor: a case report].

A 28-year-old woman was referred to our hospital complaining of upper abdominal discomfort. The patient had been receiving medical treatment for hypertension. Computed tomography revealed a 30 mm solid tumor with calcification in the left adrenal gland and a 8 mm nodule in the right adrenal gland. Endocrinological examinations revealed no activity of either adrenal mass. The left adrenal tumor was extirpated, because malignancy of the tumor was not ruled out. Histopathological examination proved that the tumor was ganglioneuroma arising from the extra-adrenal retroperitoneum.

[Significance of a simple assay of urine telomerase activity for the detection of bladder cancer].

We developed a simple urine telomerase activity assay by a modification of the TeloTAGGG telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay kit. We conjugated digoxygenin (DIG) with the CX primer of omitting hybridization of PCR products and DIG-labeled probe. The sensitivity and specificity of bladder cancer diagnosis on 100 patients with bladder cancer and 25 healthy volunteers using the simple urine telomerase activity measurement were 81% and 92%, respectively. The positive rate for bladder cancer by the present assay system was affected by neither tumor grade nor invasiveness. The diagnostic potential of the present method is superior to the conventional urine telomerase assay kit and urine nuclear matrix protein-22 (NMP22). The present method is simple, and can be used for mass screening of bladder cancer.

[Experience of laparoscopic surgery of pheochromocytoma found on induction for hemodialysis].

A 64-year-old female patient had been receiving hemodialysis since June 2008. A left adrenal mass, 2.5 cm in diameter, was incidentally found by screening computed tomography at the initiation of hemodialysis. Plasma epinephrine and norepinephrine were increased to 1.21 ng/ml and 4.71 ng/ml, respectively. In the scintiscan using ¹²³I-metaiodobenzylguanidine (MIBG), accumulation of the radionuclide in the left adrenal tumor region was confirmed. Laparoscopic left adrenalectomy was performed without peri-operative complications under the diagnosis of left pheochromocytoma. The elevated catecholamines and the blood pressure were restored after surgery.

[The giant schwannoma in the pelvic cavity: a case report].

A 62-year-old man presented with a giant tumor in the pelvic cavity that was incidentally revealed by abdominal ultrasonography. Abdominal magnetic resonance imaging showed the heterogenous tumor in the pelvis with cystic components. The tumor was 10.8 × 10.5 × 11.7 cm in diameter and adhered to the sacral wall. The tumor was extirpated following diagnosis as a benign neurogenic tumor by needle biopsy. The pelvic cavity was occupied by the tumor rigidly adhered to the sacrum. The histopathological diagnosis of the specimen was benign schwannoma, type Antoni A.

Cauda equina symptoms are closely related to male lower urinary tract symptoms.

INTRODUCTION: To determine the impact of cauda equina symptoms on male lower urinary tract function, we investigated the related risk factors in healthy Japanese men. METHODS: Subjects included 345 healthy males (average age 56 years; range 26-83) who participated in the Iwaki Health Promotion Project in 2006. They were residents of Iwaki district, Hirosaki City, northern Japan. Using a self-administered, self-reported questionnaire for lumbar spinal stenosis and International Prostate Symptom Score (IPSS), we investigated the prevalence of cauda equina symptoms. We also measured body mass index; blood pressure; and triglyceride, cholesterol, glucohemoglobin, and prostate-specific antigen levels. RESULTS: Nineteen participants (5.5%) were positive for cauda equina symptoms; 270 participants (78.3%) scored 0-7 points on the total IPSS survey, 65 (18.8%) scored 8-19, and 10 (2.9%) scored 20-35. The total IPSS, and storage and voiding symptom scores of participants negative for cauda equina symptoms were significantly lower than those who were positive. Multiple logistic regression analysis revealed that age and cauda equina symptoms were independent significant risk factors for total IPSS and storage symptoms. CONCLUSIONS: Cauda equina symptoms are closely related to lower urinary tract symptoms in healthy Japanese men.

[Relationship between tumor volume and PSA recurrence after radical prostatectomy].

We examined whether the tumor volume (TV) is a good predictor of PSA recurrence after radical prostatectomy. Data were collected for 158 patients with clinically localized prostate cancer undergoing radical prostatectomy without neoadjuvant hormonal therapy in our hospital since April 2005 to September 2007. Along with the routine pathological assessment, TV was assessed in all prostatectomy specimens. PSA recurrence was defined as PSA levels of greater than 0.2 ng/ml. The TVs were 1.81+/-1.66 ml (mean +/-SD) ranging from 0.02 to 8.20 ml. The TV in cT1c was 1.77+/-1.64, and 1.89+/-1.72 ml in cT2 (not significant). Significant differences were observed between TV and pT. The TVs in pT2a, pT2b and pT3/4 were 0.54+/-0.54, 1.63+/-1.47 and 2.67+/-1.80 ml, respectively. The median follow-up period was 32.3 months (range from 15 to 45) after radical prostatectomy, and PSA recurrence was observed in 32 cases. Patients with smaller TV (TV <1.3 ml) had a higher PSA-free survival rate (89.5%) than those with a larger TV (TV > or = 1.3 ml, 66.7%) with a significant difference atp <0.001 (log-rank test). A multivariate analysis was performed for PSA, TV, pT, Gleason Score (GS), and surgical margins. Significant differences were observed for GS, and surgical margins, but not for TV. Clinically organ-confined disease in Japanese patients with prostate cancer included various cancers from clinically insignificant to locally advanced ones. In our series, TV was not regarded as a predictor of PSA recurrence after radical prostatectomy.