[THE EFFECT OF LOW-DOSE INTRAVESICAL BACILLUS CALMETTE-GUÉRIN (BCG) INFUSION THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER].

(Objective) Bacillus Calmette-Guérin (BCG) intravesical infusion therapy plays an important role in the treatment of patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Our institute performs low-dose (40 mg) BCG intravesical infusion therapy (completed 8 times) to reduce side effects. We retrospectively investigated its efficacy and side effects. (Patients and methods) We analyzed the response, non-recurrence, and side effect rates by risk stratification in 179 patients who received low-dose BCG intravesical infusion therapy from September 2003 to November 2018 in Nagano Municipal Hospital. Complications were classified using the Common Terminology Criteria for Adverse Events version 4.0. (Results) The median age was 73 years, and the male/female ratio was 137:42. The median observation period was 32 months, and infusion was completed 8 times in 149 cases (83.2%). The overall response rate was 88.8%. The response rate was significantly higher in the low-grade pathology group than in the high-grade group. However, no significant differences in G1/G2/G3 side effects, sex, age, presence of carcinoma in situ (CIS), depth of invasion, purpose of administration, and grade of side effects were observed. The overall non-recurrence rates were 91.8%, 76.7%, and 71.3% at 1, 3, and 5 years, respectively. Nevertheless, there were no significant differences in the non-recurrence rates with respect to depth of penetration, the degree of dysmorphism, purpose of administration, presence of CIS, and completed of infusion. A total of 71 G2 side effects (39.7%) were identified, and 3 cases of G3 side effects required hospitalization. (Conclusion) In our institution, the completion rate of low-dose BCG intravesical infusion therapy was high, with few side effects. Furthermore, it demonstrated similar therapeutic effect to that reported with standard-dose administration. Low-dose BCG intravesical infusion therapy may be an effective treatment, particularly for pathologically low-grade NMIBC.

Comparison of efficacy and safety of 1- and 3-month luteinizing hormone-releasing hormone agonist depots as initial therapies for prostate cancer.

BACKGROUND: We compared the efficacy and safety of 1- and 3-month depots of the luteinizing hormone-releasing hormone (LH-RH) agonist goserelin acetate in prostate cancer patients. METHODS: Patients were randomly assigned to the Direct Group that received the goserelin 3-month depot or the Switch Group that began with the 1-month depot for the first 3 months and then switched to the 3-month depot. All patients were co-administered the antiandrogen agent bicalutamide. Serum testosterone and prostate-specific antigen (PSA) levels and adverse events were recorded at weeks 4, 8, 12, and 24. RESULTS: Baseline testosterone levels in the Direct and Switch Groups were 4.98 and 5.07 ng/mL, respectively (P = 0.798). At each week, the levels in both groups were ≤0.50 ng/mL (castration level) with no significant differences between them. All of the patients in the Switch Group and 98.1 % in the Direct Group had achieved castration levels at week 12, and 100 % had achieved such levels at week 24. Baseline PSA levels in the Direct and Switch Groups were 52.37 and 46.72 ng/mL, respectively (P = 0.793). Levels in both groups dropped continuously, to about 1.0 ng/mL at week 24, with no significant differences between the groups at any time. Three patients in the Direct Group experienced adverse events that were attributed to the co-administered bicalutamide. CONCLUSIONS: There was no difference in the efficacy or safety between the 1- and 3-month depots of goserelin when given as initial prostate cancer treatment in combination with bicalutamide. Patients must be monitored for adverse events associated with bicalutamide.

[Clinical evaluation of lower urinary tract symptoms following seed implant for prostate cancer].

A total of 320 localized prostate cancer patients including 272 at low-risk and 48 at intermediate-risk were treated with permanent iodine-125 seed implants. Changes of lower urinary tract symptoms after the treatment were analyzed for one consecutive year using international prostate symptom score, quality of life (QOL) score and uroflowmetry. These patients did not have prostate hypertrophy or were not treated with any α1 blocker before the seed implant. Tamsulosin (0.2 mg/day) was prophylactically administered to all the patients for six months beginning the day after the seed implant. Both voiding and storage symptoms developed even in patients without any urinary symptoms before seed implant and worsened during the consecutive three months; and, QOL also worsened after seed implant. Lower urinary tract symptoms continued to be significantly severe for six months compared with that before the seed implant, then improved gradually to almost the initial level after one year. It seems to take longer for storage symptoms to diminish to the initial level compared with voiding symptoms. Neoadjuvant hormone therapy improved neither voiding nor storage symptoms in patients without prostate hypertrophy less than 40 ml in volume. In conclusion, a more effective α1 blocker or other potent prophylactic drug therapy should be used on the patients after seed implant because the disadvantage of seed implant is probably only urinary disturbance.

Genital abnormalities in Pallister-Hall syndrome: Report of two patients and review of the literature.

We describe two patients with Pallister-Hall syndrome (PHS) with genital abnormalities: a female with hydrometrocolpos secondary to vaginal atresia and a male with micropenis, hypoplastic scrotum, and bilateral cryptorchidism. Nonsense mutations in GLI3 were identified in both patients. Clinical and molecular findings of 12 previously reported patients who had GLI3 mutations and genital abnormalities were reviewed. Genital features in the male patients included hypospadias, micropenis, and bifid or hypoplastic scrotum, whereas all the females had hydrometrocolpos and/or vaginal atresia. No hotspot for GLI3 mutations has been found. The urogenital and anorectal abnormalities associated with PHS might be related to dysregulation of SHH signaling caused by GLI3 mutations rather than hormonal aberrations. We recommend that clinical investigations of genital abnormalities are considered in patients with PHS, even those without hypopituitarism.

Diffusion weighted imaging in the detection of upper urinary tract urothelial tumors.

PURPOSE: Diffusion-weighted (DW) magnetic resonance imaging (MRI) provides information about the biophysical properties of tissues such as cell organization and density. DW imaging (DWI) is becoming important in the assessment of malignant tumors. The purpose of our study was to evaluate the capability and reliability of DWI in the evaluation of upper urinary tract urothelial tumors. MATERIALS AND METHODS: DWI was performed in seventeen patients with upper urinary tract urothelial tumor, previously diagnosed by either CT or retrograde pyelography. An histological evaluation was performed after surgical resection. Each MRI was carried out using a 1.5T superconductive magnet MRI system. DWI images were obtained with b value of 1000 s/mm(2) under normal breathing. The apparent diffusion coefficient (ADC) values were measured. RESULTS: In nine patients with renal pelvis tumors and seven patients with ureteral tumors, the lesions were shown as high-signal intensity in the corresponding region on DWI. In one patient with carcinoma in situ (CIS) of the ureter, the lesion was not depicted with DWI. The mean ADC value of the tumor was 1.125 + or - 0.217 x 10(-3) mm(2)/s and was significantly lower than those of the renal parenchyma (1.984 + or - 0.238 x 10(-3) mm(2)/s, p < 0.01) and the urine (2.941 + or - 0.315 x 10(-3) mm(2)/s, p < 0.01). CONCLUSIONS: In our study, the renal pelvic and ureteral tumors except CIS were shown clearly with DWI. Although further studies are required, DWI may take the place of invasive retrograde urography for detecting tumors of the upper urinary tract.

Diffusion weighted imaging in the detection of upper urinary tract urothelial tumors

Purpose: Diffusion-weighted (DW) magnetic resonance imaging (MRI) provides information about the biophysical properties of tissues such as cell organization and density. DW imaging (DWI) is becoming important in the assessment of malignant tumors. The purpose of our study was to evaluate the capability and reliability of DWI in the evaluation of upper urinary tract urothelial tumors. Materials and methods: DWI was performed in seventeen patients with upper urinary tract urothelial tumor, previously diagnosed by either CT or retrograde pyelography. An histological evaluation was performed after surgical resection. Each MRI was carried out using a 1.5T superconductive magnet MRI system. DWI images were obtained with b value of 1000 s/mm2 under normal breathing. The apparent diffusion coefficient (ADC) values were measured. Results: In nine patients with renal pelvis tumors and seven patients with ureteral tumors, the lesions were shown as high-signal intensity in the corresponding region on DWI. In one patient with carcinoma in situ (CIS) of the ureter, the lesion was not depicted with DWI. The mean ADC value of the tumor was 1.125 ± 0.217 x 10-3 mm2/s and was significantly lower than those of the renal parenchyma (1.984 ± 0.238 x 10-3 mm2/s, p < 0.01) and the urine (2.941 ± 0.315 x 10-3 mm2/s, p < 0.01). Conclusions: In our study, the renal pelvic and ureteral tumors except CIS were shown clearly with DWI. Although further studies are required, DWI may take the place of invasive retrograde urography for detecting tumors of the upper urinary tract.

Leiomyosarcoma of the urinary bladder in a patient with bilateral retinoblastoma.

We report a case of bladder leiomyosarcoma in a 27-year-old woman who had previously been treated with surgery and radiation for bilateral retinoblastoma. The patient was admitted to hospital with discomfort on micturition. Cystoscopy revealed a bladder tumor covered by normal urothelium. Transurethral resection of the bladder tumor was performed, and the histopathological diagnosis was leiomyosarcoma. Partial cystectomy was performed. The leiomyosarcoma of the bladder did not invade the muscle layer. However, bladder tumors recurred at new intravesical locations repeatedly. After transurethral resection of the bladder tumor had been performed twice, total cystectomy and creation of an ileal conduit were performed.

[Preoperative magnetic resonance imaging in the management of the nonpalpable testis].

We evaluated the efficacy of magnetic resonance imaging (MRI) as the preoperative study in the management of the nonpalpable testis. From 1997 to 2005, a total of 41 MRI was performed for the patients with nonpalpable testis and 42 testes were evaluated. The MRI showed 19 testes from 18 patients in the inguinal region. Eighteen testes were found in the inguinal region and one was intraabdominal during groin exploration. Six testes were pointed out to be intra-abdominal by MRI. Five testes were identified in the abdomen and one was disclosed to be vanishing testis. Seventeen testes could not be detected by MRI and they underwent laparoscopic or groin exploration. Four abdominal testes were identified. Thirteen patients had a diagnosis of vanishing testis. The sensitivity and the specificity of our MRI studies in predicting the presence of nonpalpable testis were 85.7% and 92.9%, respectively. Enlarged lymph node could be misdiagnosed as abdominal testis. Inguinal undescended testes can be diagnosed accurately with MRI. MRI is informative regarding the testis location and useful for limiting the area of surgical exploration.

[Sarcomatoid renal cell carcinoma with von Hippel-Lindau disease: a case report].

We report a 68-year-old woman who had bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau (VHL) disease. Surgical resection of a central nervous system hemangioblastoma had been done previously. This time, synchronous bilateral RCCs were found in her kidneys, with metastases to lungs and liver. Right radical nephrectomy was performed to remove the primary tumor in the right kidney. Histopathological examination of the tumor revealed clear cell RCC with a sarcomatoid component. After surgery, transcatheter arterial embolization was performed for the tumor in the left kidney and interferon therapy was commenced. The left renal tumor decreased in size and interferon therapy was effective against the metastatic lung tumors. However, 4 years after resection of the right RCC, the tumor in the left kidney increased progressively in size and partial left nephrectomy was performed. Histopathological examination of the resected tumor also showed clear cell type RCC with a sarcomatoid component. The patient eventually died of her disease at 5 years after resection of the right RCC. RCC associated with VHL is usually of the clear cell type has a relatively good prognosis. Sarcomatoid RCC is rare in VHL patients and, to our knowledge, the present report is the first case of sarcomatoid RCC associated with VHL in the Japanese literature.

Permanent prostate brachytherapy for Japanese men: results from initial 100 patients with prostate cancer.

OBJECTIVE: To evaluate the initial results of brachytherapy for prostate cancer with permanent iodine-125 implant in Japan. METHODS: The results obtained with brachytherapy in the initial 100 Japanese patients treated at Nagano Municipal Hospital were reviewed. Patients with a prostate-specific antigen (PSA) level of less than 10 ng/mL and a Gleason's scores of 5, 6, 3 + 4 were classified as having a low risk of recurrence. Patients with a PSA level of 10-20 ng/mL and/or a Gleason's score of 4 + 3 were classified as having an intermediate risk for recurrence. Seventy-eight of the low-risk patients and 19 of the intermediate-risk patients were treated by seed implants alone, or seed implants combined with preceding external radiation, respectively. A total of 53 patients received neoadjuvant hormone therapy. The efficacy and morbidity of brachytherapy were investigated using the serum PSA, International Prostate Symptom Score, quality of life score and uroflowmetry data. RESULTS: The average V100 and D90 obtained by post-implant dosimetry was 94.3 and 113.7%, respectively. Serum PSA decreased gradually after treatment, although it had still not reached a nadir after 1 year. There was little difference of the PSA level between the patients with and without neoadjuvant hormone therapy even at 1 year after seed implantation. There were no PSA biochemical failure or clinical recurrence during the follow-up period. Voiding symptoms worsened until 3 months after treatment, and then gradually improved. Acute urinary retention occurred transiently in one patient (1%). Rectal bleeding and severe diarrhea did not occur. CONCLUSION: Brachytherapy is a feasible and effective option for the treatment of prostate cancer in Japanese men. Brachytherapy may have a different effect in Japanese patients with respect to voiding symptoms. Urinary retention was rare, but voiding symptoms were persistent in Japanese patients. Neoadjuvant hormone therapy deserves investigation to determine whether it can achieve better results, especially in patients with an intermediate risk.

[Adrenal pseudocyst; a case report].

We report a case of adrenal pseudocyst. A 35-year-old woman presented with palpation of right upper abdominal mass without tenderness. Abdominal computed tomographic scan showed a right retroperitoneal cystic mass 20 cm in diameter. The patient underwent complete resection of the mass, including the normal adrenal gland. The cyst contained 3100 ml of dark brown thrombotic liquid. Histopathological examination revealed adrenal pseudocyst with a thick figrocollagenous wall. The normal adrenal gland was compressed by the wall. Adrenal pseudocyst is a rare disease. The mechanisms of adrenal pseudocyst formation and their expanding nature are discussed.

[Novel NMP22 quick qualitative analysis (BladderChek NMP22) for the diagnosis of urothelial tumor].

PURPOSE: The BladderChek NMP22 test was studied to determine whether it could be a useful diagnostic tool for urothelial tumor. MATERIALS AND METHODS: During the period from April to May 2004, a total of 50 patients who visited Nagano Municipal Hospital were subjected to analysis with the BladderChek NMP22 test. They consisted of 25 patients with microscopic or gross hematuria and 25 patients with urothelial tumor who were being followed after surgery. The clinical diagnosis was made by cystoscopy, abdominal CT scanning, ultrasonography or intravenous urography. BladderChek NMP22 was used in all of the patients and the test was judged to be positive when a line appeared on the glass at 30 minutes after a drop of urine was added to the sample well. Cytological examination of the urine was also done. It was defined as negative if the result was I, II or III, while it was positive if the result was IV or V. RESULTS: Seven patients who were not eligible were excluded and the remaining 43 patients were studied. Eleven of the 43 patients were diagnosed as having urothelial tumor. The sensitivity, specificity, and accuracy of BladderChek NMP22 for making a correct diagnosis was 63.6%, 62.5%, and 62.7%, respectively (p = 0.1703). As for urine cytology, the sensitivity, specificity, and accuracy was 36.3%, 100%, and 83.7%, respectively (p = 0.0027). BladderChek NMP22 was positive in all the patients whose urine cytology was positive and in three patients with low-grade, low-stage, and small tumors, although urine cytology was negative. On the other hand, false-positive BladderChek NMP22 results were obtained in patients undergoing follow-up after removal of urothelial carcinoma and in patients with urinary stones. The sensitivity of BladderChek NMP22 was superior to that of urine cytology, but its specificity was inferior. CONCLUSION: The combined use of BladderChek NMP22 and cystoscopy may be useful for the diagnosis and follow-up of urothelial tumor. On the other hand, the results obtained with BladderChek NMP22 need to be interpreted carefully because the test can yield a false-positive outcome in the presence of marked hematuria, pyuria or cytolysis of normal urotherium. When the result of BladderChek NMP22 in the monitoring of recurrent urotherial tumor following surgery was positive in spite of negative findings of cystoscopy, it is necessary to consider the presence of a tumor in the upper urinary tract or a high tendency toward tumor recurrence. In such a case, careful followup may be necessary.

[Non-ischemic partial nephrectomy using microwave tissue coagulator].

PURPOSE: The indications and the safety of non-ischemic partial nephrectomy using a microwave tissue coagulator were studied. MATERIALS AND METHODS: Non-ischemic partial nephrectomy was performed on 17 kidneys of 16 patients using a microwave tissue coagulator. The diagnosis was renal tumor and renal stones in eleven and five patients, respectively. Renal tumors were less than 4 centimeters in diameter, while the stones were associated with a caliceal diverticulum or secondary cortical atrophy. Excision of the tumors was done via the retroperitoneal approach through an oblique lumbar incision. The needle of the microwave tissue coagulator was inserted around the tumor (stone) 10 to 20 times, and the coagulator was activated. Then the tumor (stone) was excised with a sharp knife or scissors. Patients were encouraged to walk on the first postoperative day. RESULTS: Vascular clamping was necessary in one patient to reduce bleeding. Nephrectomy was done after partial nephrectomy in one patient because it was difficult to close the urinary collecting system after it was widely exposed. Although urine leakage was seen postoperatively in two patients, it ceased spontaneously at 14 and 23 days after surgery. Postoperative complications developed in one of seven patients (14%) with protruding renal tumor, in three of five patients (60%) with non-protruding renal tumor and in two patients with renal stone. Allogenic or autologous blood transfusion was not necessary, nor was any bleeding noticed post-operatively. In one patient, atrophy of the renal parenchyma occurred gradually after surgery and function was eventually lost. However, renal function was well preserved and recurrence of the problem was not observed in the other 15 patients, excluding one who died of esophageal cancer. CONCLUSIONS: The microwave tissue coagulator is a useful surgical instrument for non-ischemic partial nephrectomy, not only in patients with renal tumors but also in patients with complicated kidney stones. However, non-protruding renal tumor in a patient with solitary kidney should be avoided for this surgery. Thermal injury to the renal parenchyma or large vessels should be avoided and urine leakage from the collecting system should be meticulously treated during the operation.

De-serosalized muscle layer covering method for antireflux ureteroileostomy: a new operative technique and pressure study with ureterometry at the ureteroileal anastomotic site in dogs.

PURPOSE: In pursuit of a more effective antireflux ureteroileostomy with a lower postoperative complication rate we performed a new operative technique and evaluated intraureteral pressure with ureterometry to examine the mechanism of antireflux function. MATERIALS AND METHODS: A total of 11 beagle dogs were used in this study. A 3 x 2 cm. section of the ileal serosa was removed, the severed ureter was directly anastomosed to the de-serosalized area and 1 cm. of terminal ureter and the direct anastomotic site were covered with the de-serosalized ileal wall. The bladder was augmented with the ileum containing the ureter. Postoperative evaluations were performed monthly and ureterometry of the reimplanted ureter was done 6 months postoperatively. RESULTS: Complete reflux prevention and a low stricture rate were achieved with this procedure. Direct ureteroileal anastomosis caused stricture in 1 of the 11 ureters but the covering procedure to prevent ureteral reflux caused no ureteral strictures. When the bladder was empty, ureteral closure pressure at the intramural portion of the ureter was low. At the phase of high intravesical pressure ureteral closure pressure at the intramural ureter was as high as intravesical pressure. CONCLUSIONS: The de-serosalized muscle layer covering method prevented ureteral reflux completely with a low stricture rate. The antireflux function of this method seems to depend on the flexibility of the terminal ureter covered with the de-serosalized ileal wall. Reflux prevention in the low intravesical pressure phase seems to be due to extension of the ileal wall.