A rare manifestation of IgG4-related disease and secondary hypereosinophilic syndrome: A case report.

We report a case of IgG4-related disease (IgG4-RD) with marked eosinophilia. A 79-year-old woman was admitted due to diarrhoea and weight loss. Cervical lymphadenopathy, bilateral submandibular glands swelling, anaemia (Hb8.5 g/dl), hypereosinophilia (9750/µl), elevated serum creatinine (1.57 mg/dl), pancreatic amylase (191 IU/l), and IgG4 (3380 mg/dl) were found. Diffusion-weighted image on magnetic resonance imaging showed high-intensity signals inside both the pancreas and the kidneys. The echogram of submandibular glands revealed cobblestone pattern. Kidney biopsy revealed acute tubulointerstitial nephritis. Biopsies of lip, gastrointestinal tract, and bone marrow showed infiltration of lymphoplasmacytic cells and IgG4-positive plasma cells (30-67/HPF). Gastrointestinal and bone marrow biopsies also showed eosinophilic infiltration. Adrenal insufficiency, rheumatic disease, tuberculosis, parasite infection, drug-induced eosinophilia, and eosinophilic leukaemia were all ruled out. We started treatment with 40 mg of prednisolone (PSL) and her general condition rapidly improved. The eosinophil count, serum IgG4, and serum creatinine decreased. We gradually tapered PSL and maintained 5 mg/day. During the 5 years of treatment, she had no recurrence of the symptom. According to the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, eosinophils >3000/µl is one of the exclusion criteria. If we comply with this criterion, the diagnosis of IgG4-RD should be avoided. However, our case fit the diagnostic criteria of type I autoimmune pancreatitis, IgG4-related sialadenitis, and global diagnosis of IgG4-RD. We finally diagnosed our case as IgG4-RD with secondary hypereosinophilic syndrome. This case suggests that IgG4-RD with eosinophils >3000/µl does exist in the real world.

A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier. CASE PRESENTATION: A 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of "decoy cells". Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy. CONCLUSIONS: BKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.

Risk factor for progression to kidney failure with replacement therapy in elderly patients with chronic kidney disease: A retrospective single-centre cohort study.

BACKGROUND: Although the number of elderly patients with chronic kidney disease (CKD) has increased, few studies have examined their prognosis. METHODS: The study design was a retrospective cohort study at a single centre. We evaluated 301 patients aged ≥75 years old with CKD stage G3a to G5. The primary endpoint was kidney failure with replacement therapy (KFRT) and secondary endpoints were all-cause mortality and annual decline rates of estimated glomerular filtration rate (eGFR). The incidence of KFRT was estimated using the cumulative incidence method considering the competing risk of death. To identify the independent risk factors related to KFRT, multivariate Fine-Gray regression model analysis were performed. RESULTS: The median age of the patients was 79 years and the median eGFR was 24.0 mL/min/1.73 m2 at baseline. Urinary protein was positive in 70% of patients. With a median follow-up of 24.5 months, 35% of the patients developed KFRT and 9% died. Kidney survival significantly decreased according to the CKD stage at baseline. In patients without proteinuria, the cumulative incidence of KFRT increased in CKD stage G5 patients, while in patients with proteinuria, the incidence of KFRT increased from patients with CKD stage G3b. Multivariate Fine-Gray regression model revealed that less aged, CKD stage G5, baseline data such as proteinuria, hypoalbuminemia, hyperphosphatemia, and hyperuricemia were independent risk factors for KFRT. CONCLUSION: Elderly CKD patients with proteinuria need to be carefully monitored even at an early CKD stage because of the risk of developing KFRT.

Distribution of the positive UPOINT domain in patients with chronic prostatitis or chronic pelvic pain syndrome: A multicenter observational study.

OBJECTIVE: To determine the UPOINT-positive domain numbers and evaluate the significance of the sexual dysfunction domain in patients with chronic prostatitis or chronic pelvic pain (CP/CPPS) in Japan. METHODS: A total of 58 patients with CP/CPPS with moderate or greater symptoms were included. Symptom severity was determined by > 14 on the chronic prostatitis symptom index (CPSI). The main outcome was to confirm the number and distribution of the positive UPOINT domains in this group. As secondary outcomes, the correlation between positive domain numbers and CPSI scores was evaluated. We also examined whether the sexual dysfunction subdomain, as determined by the five-item international index of erectile function, could improve the correlation with symptom severity. RESULTS: The mean age was 48.6 ± 15.4 years, CPSI score 24.3 ± 6.1, and positive UPOINT domain number 2.4 ± 0.9. The distribution of each positive domain was 67.2% for urinary, 15.5% for psychosocial, 75.8% for organ-specific, 3.4% for infection, 5.1% for neurological/systemic conditions, and 75.8% for tenderness. Although the mean CPSI total scores tended to increase with an increasing number of positive UPOINT domains, a significant correlation was not observed (r = 0.134, p = 0.312). The sexual dysfunction domain was positive in 62.0% of the cases, but the correlation could not be improved. CONCLUSIONS: Urinary, organ specific, and tenderness domains were mainly observed in patients with CP/CPPS. When patients with moderate or grater CPSI scores are clinically evaluated, clinicians should recognize that the UPOINT-positive domain and CPSI score are clinically and pathologically different concepts. (250 words).

Clinicopathological significance of light chain deposition in IgA nephropathy.

BACKGROUND: Clinicopathological significance of light chain deposition in IgA nephropathy and the relation of monotypic IgA deposition to bone marrow abnormalities are important issues to be clarified. METHODS: We retrospectively investigated light chain deposition in 526 patients with IgA nephropathy. We divided the patients into 5 groups according to the balance of intensity of both light chain deposition: lambda monotypic, lambda dominant, polytypic, kappa dominant and kappa monotypic. Clinicopathological parameters were compared among the groups. The relation of monotypic IgA deposition to hematological malignancy was also evaluated. RESULTS: The prevalence of monotypic IgA deposition was 6.3%, 33 patients (21 lambda and 12 kappa). Thirty-two (4.0%) and 10 patients (1.9%) were classified into lambda and kappa dominant groups, respectively. Polytypic IgA deposition was observed in 455 patients (85.7%). Age of onset, age at biopsy, urinary protein creatinine ratio, the percentage of global glomerulosclerosis, and the degree of IgA and C3 deposition were different among the groups. However, there was no gradual difference according to the groups. No patient with monotypic IgA deposition showed hematological abnormality at biopsy and during follow-up. CONCLUSIONS: The prevalence of IgA monotypic deposition was extremely low. Clinicopathologically, we could not differentiate patients with monotypic IgA deposition from those with polytypic one and no hematological disorder was documented in patients with monotypic IgA deposition. Whether IgA nephropathy with monotypic IgA deposition and that with polytypic one is the same entity or not, and relation between monotypic IgA deposition and hematological malignancy should be clarified by further investigations.

The first case of COVID-19 pneumonia in a hemodialysis patient in Japan.

On 31 December 2019, cases of pneumonia whose cause was later identified as SARS-CoV-2 were detected in Wuhan City, Hubei Province of China, and now COVID-19 has spread worldwide. On March 1, 2020, a 69-year-old Japanese man who had been on hemodialysis for 3 years was diagnosed as having COVID-19 pneumonia and hospitalized at our Medical Center. Pulmonary CT revealed bilateral multiple consolidation with bilateral pleural effusion. Aggressive weight reduction was needed to improve the patient's respiratory condition. Hemodialysis therapy was performed in isolation with hydroxychloroquine administration, but the formation of a dialysis membrane clot forced the withdrawal of dialysis therapy. Changing the dialysis membrane material and anticoagulant enabled the resumption of dialysis therapy, allowing the body weight to correct downward. On the 5th hospitalization day, the patient's fever dropped and he showed improved oxygenation and chest X-ray. He was eventually discharged. The hydroxychloroquine and appropriate fluid management may have contributed to the patient's recovery. Clinicians should pay close attention to avoid dialysis-related problems when treating a patient with COVID-19.

Comprehensive evaluation of the significance of immunofluorescent findings on clinicopathological features in IgA nephropathy.

BACKGROUND: The clinicopathological significance of immunofluorescent findings in IgA nephropathy remains controversial. METHODS: The relations of the deposition of IgA, IgG, IgM, C3, C1q and fibrinogen (Fib) with pathological findings, baseline clinical findings, and renal outcome were evaluated in 688 patients with IgA nephropathy. Pathological features included cellular or fibrocellular crescents, endocapillary or mesangial hypercellularity, segmental or global glomerulosclerosis and the Oxford classification. RESULTS: The median age at biopsy was 30 years. There were 289 men. With 74 months median follow-up, 32% of patients received steroids. Twelve percent of patients developed end-stage renal disease (ESRD). The degree of IgA was closely related to the degree of C3, IgG and IgM deposition. The degree of IgA, C3, IgG and Fib deposition was significantly related to the percentage of glomeruli with crescent, endocapillary and mesangial hypercellularity. IgM deposition showed significant association with crescent, mesangial hypercellularity, segmental sclerosis, global glomerulosclerosis and tubular atrophy/interstitial fibrosis. In the patients treated with steroids, the risk for ESRD in patients with 2-3+ IgA deposition was significantly lower with reference of 1+ IgA deposition. CONCLUSION: We found the different roles of glomerular immune reactants' deposition in the inflammatory process from acute to chronic stage. IgA deposition together with IgG, Fib and C3 may produce acute inflammatory injury. IgM deposition might occur in the early stage of inflammation and remains until late sclerotic stage. The prominent deposition of IgA related to low risk for ESRD in patients who received steroids might suggest effectiveness of steroids in such patients.

Oral administration of cernitin pollen extract (Cernilton® ) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study.

OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.

Asymptomatic Brain Edema after Hemodialysis Initiation in a Patient with Severe Uremia.

A 66-year-old man with severe renal insufficiency presented with mild confusion associated with uremia. Cranial magnetic resonance imaging (MRI) showed no remarkable changes. The patient was placed on short-duration hemodialysis (2 hours) with smaller surface area and low blood flow (100 mL/min) to avoid dialysis disequilibrium syndrome (DDS). His consciousness gradually improved and he did not develop apparent DDS symptoms. However, T2-weighted FLAIR MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe on day 15. In other words, cranial MRI showed cerebral edema, indicating asymptomatic DDS. On day 29, cranial MRI showed a return to findings on admission. In this case, because the patient did not have apparent DDS symptoms despite MRI changes, we diagnosed asymptomatic cerebral edema. The patient was discharged on regular intermittent HD without any neurological deficits. No further neurological disturbances were noted during 1-year follow-up. MRI findings in ESKD patients without DDS symptoms help to clarify the diagnosis of cerebral edema. In this case, the patient did not have apparent DDS symptoms and was therefore diagnosed with asymptomatic cerebral edema.

Clinicopathological significance of monoclonal IgA deposition in patients with IgA nephropathy.

BACKGROUND: Clinicopathological significance of monoclonal IgA deposition and its relation to bone marrow abnormalities in IgA nephropathy (IgAN) remains unclear. METHODS: We retrospectively investigated the prevalence and clinicopathological significance of monoclonal IgA deposition in 65 patients with IgAN. Serum-free light chain ratio, and urinary Bence Jones protein were also measured. RESULTS: Thirty-nine percent of patients were men, median age was 40 and median observation period was 31 months. Five patients (Group M) showed monoclonal IgA lambda deposition and one showed monoclonal IgA kappa deposition. Fifty-nine patients (Group P) showed polyclonal IgA deposition. There were no significant differences in the degree of proteinuria, hematuria and renal function between Group M and Group P. Total protein and albumin were significantly lower in Group M than in Group P. According to the Oxford classification, the percentage of patients with M1 was significantly higher in Group M than in Group P. One patient in Group P showed serum monoclonal IgG lambda. No patient showed abnormal serum-free light chain ratio. Seventy-five percent in Group M and 42 % in Group P were treated with steroid. Three patients in Group P progressed to end-stage renal disease (ESRD). The frequency of disappearance of proteinuria or hematuria and progression to ESRD was not different between the groups. CONCLUSIONS: The prevalence of monoclonal IgA deposition was 9.2 %. Although some parameters differed between the groups, renal outcome were similar. Thus, IgAN with monoclonal IgA deposition seems not to be different entity from those with polyclonal IgA deposition.

Comparison of mirabegron and imidafenacin for efficacy and safety in Japanese female patients with overactive bladder: A randomized controlled trial (COMFORT study).

OBJECTIVES: To evaluate the efficacy and safety of mirabegron compared with imidafenacin for the treatment of female patients with overactive bladder. METHODS: Patients (n = 89) were randomized to receive 0.1 mg imidafenacin twice daily (n = 47) or 50 mg mirabegron once daily (n = 42) for 12 weeks. The primary efficacy end-point was change in total Overactive Bladder Symptom Score. Secondary efficacy end-points included change in Overactive Bladder Symptom Score, 3-day micturition diary, International Prostate Symptom Score and Overactive Bladder Questionnaire. Safety assessments included adverse events, vital signs, post-void residual volume and patient-reported incidence, and severity of distinctive symptoms related to adverse events. RESULTS: The mirabegron group showed a significantly reduced mean total Overactive Bladder Symptom Score from baseline, but no significant differences were noted in change of total Overactive Bladder Symptom Score compared with the imidafenacin group. Significant improvements in secondary efficacy end-points were observed regarding the mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, total International Prostate Symptom Score and quality of life in both groups, with no significant differences between the groups. The overall incidence of adverse events and the incidence of dry mouth were significantly higher in the imidafenacin group than in the mirabegron group. Patient-reported incidence and the severity of dry mouth were significantly exacerbated in the imidafenacin group. CONCLUSIONS: Treatment with 50 mg mirabegron once daily effectively relieves overactive bladder symptoms in women with fewer adverse events than treatment with antimuscarinics.

Obstructive pyelonephritis as a result of urolithiasis in Japan: diagnosis, treatment and prognosis.

OBJECTIVES: To study the current scenario of diagnosis, treatment and mortality of obstructive pyelonephritis secondary to urolithiasis in Japan. METHODS: The study was a retrospective and multicenter survey for hospitalized patients with obstructive pyelonephritis as a result of urolithiasis in educational facilities for specialists by the Japanese Urological Association. Patients' characteristics including physical or laboratory examinations, treatment and prognosis were recorded, and the risk factors for disease death were analyzed. RESULTS: A total of 1363 patients from 208 hospitals were analyzed. The median age of patients was 68 years, and there were 2.2-fold more female patients than male patients. From 844 patients, 891 species of bacteria or fungi were isolated, and Gram-negative rods accounted for 76.5% of cases. The mortality of patients was 2.3%. The risk factors related to disease death by univariate analysis were identified as older age, solitary kidney, ambulance use to visit hospital, disturbance of consciousness, severe appetite loss, higher performance status, disseminated intravascular coagulation status or systemic inflammatory response syndrome, vasopressors and anti-disseminated intravascular coagulation therapies, increased pulse rates, lower hemoglobin, lower serum albumin, and high blood urea nitrogen values. The predictive risk factors for disease death of patients' status at hospitalization were age over 80 years, systemic inflammatory response syndrome, disseminated intravascular coagulation status, disturbance of consciousness and solitary kidney by multivariate analysis. CONCLUSIONS: Obstructive pyelonephritis as a result of urolithiasis represents an emergent disease in the urological field with relatively high mortality. Patients with older age or poor conditions should be hospitalized, and intervention by a urology specialist is likely to be required.

Changes in perioperative management of radical prostatectomy using clinical pathways according to a standardized care plan: a multi-institutional study.

OBJECTIVES: To improve the perioperative care for radical prostatectomy patients at a multi-institutional level and practice. METHODS: A prospective multi-institutional study involving 50 hospitals was carried out in cooperation with the Japanese Society of Endourology. As the first step, a consensus meeting was held to establish a standardized perioperative care plan. Second, the clinical pathways were individually developed and revised according to the standardized care plan in each of the participating hospitals. Patterns of perioperative care, including preoperative hospital stay, resuming meals and ambulation, removal of pelvic drain and urethral catheter, antimicrobial administration, and postoperative hospital stay, were compared before (2007) and after developing/revising pathways (2009). Furthermore, actual practice and complications before and after implementing the pathways were investigated. RESULTS: Except for resuming ambulation, all perioperative pathways were significantly shortened with the adoption of the newly defined clinical pathway (P < 0.001). Furthermore, all settings except for postoperative hospital stay significantly decreased in terms of variance (P < 0.002). In 2009, the overall complication rate significantly decreased (P < 0.001), and all of the outcomes except urethral catheter removal were also significantly shortened (P ≤ 0.008) and decreased in variance after implementation of the new pathways (P ≤ 0.006). In multivariate analyses, implementation of the refined clinical pathways was an important factor to improve perioperative care. CONCLUSIONS: When standardized goals in perioperative care are recommended to hospitals and care plans are developed/revised in individual hospitals, both settings and practice are significantly improved. It is to be investigated whether a similar intervention could be useful to achieve a standardization of surgical pathway for other diseases.

Fever associated with severe dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA) is one of the most important complications in patients on long-term hemodialysis (HD). DRA often affects the osteoarticular system; however, little is known about the role of ß2-microglobulin in the induction of fever in HD patients. We report a 64-year-old woman on long-term (24 years) HD who developed polyarthralgia and intermittent fever. Infectious diseases, connective tissue diseases, and malignant neoplasm were ruled out. Computed tomography and magnetic resonance imaging showed swelling of the soft tissues around bilateral shoulder and hip joints, suggestive of amyloid deposits. Gallium scintigraphy showed abnormal uptake in the vicinity of several large joints. It was presumed that the fever was related to the amyloid joint deposits, and the patient was treated with prednisolone and ß2-microglobulin adsorption therapy. The treatment resulted in the resolution of fever, relief of arthralgia, and normalization of several inflammatory cytokines and C-reactive protein. The findings suggest that massive DRA could cause systemic inflammatory response in patients on long-term HD.

Osteomalacia secondary to renal tubular acidosis due to Sjögren's syndrome: a case report and review of the literature.

A 43-year-old woman was admitted to our hospital because of generalized bone pain. Arterial blood gas showed pH 7.266, HCO3- 13.5 mEq/l, and anion gap (AG) 12. Since her urine pH was 7.0 despite metabolic acidosis with normal AG, we diagnosed distal renal tubular acidosis (RTA). Serum phosphate was 2.5 mg/dl, the level of ß2 microglobulin was 41100 µg/l, and aminoaciduria was present. These results indicated proximal tubular dysfunction. The radiograph showed pseudofracture in the pubic bone, indicating osteomalacia. Bone scintigram showed abnormal accumulations of 99mTc-HMDP in multiple joints. Then, her generalized bone pain was considered to be a symptom of osteomalacia. Despite the absence of overt Sicca syndrome, the evaluation of Sjögren's syndrome (SjS) as a cause of distal RTA was performed. Antibodies to the SS-A level was 127U/ml. Tear break-up time was 3 s bilaterally and salivary gland scintigraphy showed low uptake of 99mTc in the submandibular glands and the parotids. Thus, we diagnosed SjS finally. Gallium scintigraphy showed mild abnormal uptake in bilateral kidneys, suggesting acute tubulointerstitial nephritis. After treatment with prednisolone, alfacalcidol, and sodium bicarbonate, bone pain was remarkably relieved. Additionally, aminoaciduria disappeared and the level of ß2 microglobulin decreased. We speculated that the coincidence of proximal tubular dysfunction and distal RTA cause a severe manifestation of osteomalacia.

Retrograde endoscopic management of ureteral stones more than 2 cm in size.

OBJECTIVES: To verify the safety and efficacy of retrograde endoscopic lithotripsy as the treatment modality for large ureteral stones. METHODS: From July 1996 to May 2005, we performed retrograde endoscopic treatment in 54 patients with large ureteral stones more than 2 cm in size, using a small-caliber ureteroscope and a holmium:yttrium-aluminum-garnet laser lithotriptor. Although the mean maximal stone diameter was 2.4 cm, 6 patients had stones measuring larger than 3 cm. Of the 54 patients, 11 had stones that could not be effectively fragmented by shock wave lithotripsy previously. RESULTS: Of the 54 patients, 48 were treated solely using retrograde ureteroscopy. In 47 patients (87%), the stones were fragmented completely by a single endoscopic procedure. Additional shock wave lithotripsy was performed after endoscopic debulking in 2 patients, and any stones remaining in the ureter were easily treated by shock wave lithotripsy. Pyelonephritis resulting from obstruction caused by ureteral stones was observed in 4 patients, 3 of whom required percutaneous nephrostomy and 1 of whom required stent insertion before the endoscopic procedure. These patients then underwent retrograde endoscopic lithotripsy, which completely cleared the calculi in one session. No intraoperative complications occurred. The only postoperative complication was found in 1 patient presenting with a ureteral stricture. One month after the final treatment, no patients had evidence of residual stones. CONCLUSIONS: With use of a small-caliber ureteroscope and a holmium:yttrium-aluminum-garnet laser lithotriptor, retrograde endoscopic lithotripsy seems to be an effective first-line therapy for large ureteral stones measuring more than 2 cm in size.

Retrograde endoscopic laser therapy and ureteroscopic surveillance for transitional cell carcinoma of the upper urinary tract.

OBJECTIVE: To investigate the efficacy of endoscopic laser therapy and ureteroscopic surveillance for transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: Tumors of the upper urinary tract were detected at ureteroscopy. After TCC was diagnosed by biopsy, retrograde endoscopic laser therapy was performed. Recurrent tumors were treated endoscopically and the patients were followed by ureteroscopic surveillance at 3- to 6-month intervals. RESULTS: Seven patients underwent ureteroscopic treatment. The tumor was grade 1 in five patients and grade 2 in two patients. The average tumor size was 1.3 cm. One patient with large, multifocal tumors died of metastatic disease, and one died of an unrelated cause. One patient requested nephroureterectomy after endoscopic treatment. The remaining four patients were followed up for a mean of 32 months after initial treatment. Each patient received an average of 5.3 ureteroscopic surveillance procedures while 3.3 recurrences on average were detected. Recurrence occurred in all the patients who showed normal radiographic findings. Urine cytology was also of little value in predicting tumor recurrence, except in one patient with carcinoma in situ. The recurrent tumors detected by ureteroscopy were successfully treated by repeated endoscopic procedures. After the follow up, three patients remained alive with no signs indicative of disease, but one patient with an initial grade 2 tumor died of recurrence after 30 months. CONCLUSIONS: Given that ureteroscopic evaluation is essential for surveillance after endoscopic treatment of upper urinary tract TCC because of residual concern about recurrence, patients treated endoscopically should be recommended to undergo long-term endoscopic follow up.

Long-term outcome of a low-dose intravesical bacillus Calmette-Guerin therapy for carcinoma in situ of the bladder: results after six successive instillations of 40 mg BCG.

BACKGROUND: In Japan, bacillus Calmette-Guerin (BCG: Tokyo 172 strain) instillation is generally performed at a dose of 80 mg once weekly for eight consecutive weeks; however, many adverse effects including severe ones have been reported. We employed a dose of 40 mg once a week for six consecutive weeks in principle for carcinoma in situ (CIS) of the bladder, and retrospectively evaluated its effectiveness and safety. METHODS: A total of 43 patients with CIS of the bladder were treated by this method and followed-up for a subsequent 12-79 months (median, 54 months). The patients consisted of 35 males and eight females aged 45-87 years (mean, 67.5 years). Intravesical BCG instillation at a dose of 40 mg was conducted once a week for six consecutive weeks. RESULTS: A complete response (CR) was achieved in 84% of the patients, in whom the recurrence-free rate was 72.4% after 3 years and 61.9% after 5 years. The median CR duration was 37.5 months. Two patients underwent total cystectomy, but none died of bladder cancer. As adverse effects, bladder irritation symptoms were observed in 48.8%, pyuria in 46.5%, macroscopic hematuria in 18.6% and fever (>37.5 degrees C) in 9.3%. There were no severe adverse effects requiring discontinuation of drug administration. CONCLUSION: Our present study corroborated both the effectiveness and safety of low-dose BCG therapy for CIS of the bladder. This therapy warrants further study by prospective randomized trials in the future.

[Intravesical Bacillus Calmette-Guerin (BCG: Tokyo 172 strain) instillation for carcinoma in situ of the bladder: results with 6 successive instillations of 40 mg BCG].

We performed a study to evaluate the usefulness of intravesical Bacillus Calmette-Guerin (BCG: Tokyo 172 strain) instillation on carcinoma in situ (CIS) of the bladder. Between 1998 and 2003, 43 patients were treated for CIS of the bladder with a median follow-up period of 45 months (range: 12 to 69 months). The patients (35 males and 8 females) ranged in age from 45 to 89 years (average: 67.5 years). They underwent intravesical instillation of 40 mg of BCG once a week for 6 weeks. A complete response (CR) was achieved in 83.7% of the patients. Among these patients, 97.2% and 70.7% remained recurrence-free during follow up for one year and three years, respectively. The median duration of CR was 31.5 months. Although total cystectomy was performed on 1 patient, none of the patients died of bladder cancer. Adverse effects included bladder irritability in 48.8%, pyuria in 46.5%, gross hematuria in 18.6%, and fever (temperature over 37.5 degrees C) in 9.3%. No clinically significant side effects were observed. These results indicate that intravesical instillation of BCG at a dose of 40 mg given 6 times was as effective as the routine dose of 80 mg, and could decrease systemic adverse effects such as high fever.