Fourth national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from patients with complicated urinary tract infections.

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.

Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

[Bladder Cancer Detected Incidentally by Cystoscopy before Radical Prostatectomy].

Radical prostatectomy is the treatment of choice for localized prostate cancer. In our institution, preoperative cystoscopy is performed routinely to clarify the prostate anatomy, including the median lobe and position of ureteral orifices. We conducted a retrospective analysis of 721 patients, from January 2008 to December 2022, our aim being to assess the clinical course of bladder cancer discovered incidentally through cystoscopy prior to radical prostatectomy. We found that bladder cancer was detected in eight of these patients (1.1%), seven of whom had low-grade, non-invasive, papillary urothelial carcinomas ; the remaining patient had a high-grade lesion. Notably, the pathological stage was Ta in all cases. The median duration of follow-up of patients with bladder cancer was initially set at 21 months (12-24 months). During the follow-up period, bladder cancer recurrence was identified in three patients. Patients who remained recurrence-free beyond the follow-up period underwent radical therapy. Importantly, no evidence of prostate cancer progression was detected throughout the follow-up period. Thus, incidental bladder cancer detected prior to radical prostatectomy is predominantly non-invasive, ensuring safe treatment of both the bladder and prostate cancers. Our findings suggest that cystoscopy could be omitted.

[A Case of Aldosterone-Producing Adrenocortical Carcinoma].

A 59-year-old man presented with high blood pressure, hypokalemia and muscle weakness. His aldosterone/renin ratio was high and plasma renin activity was low. Computed tomography (CT) showed a heterogeneous left adrenal mass. Primary aldosteronism was diagnosed and laparoscopic left adrenalectomy was performed. The pathological diagnosis was adrenocortical carcinoma with positive surgical margins. He underwent radiotherapy and mitotane as adjuvant therapies. Subsequently, CT revealed multiple metastases, in the liver and retroperitoneum. After six courses of EDP (a combination of etoposide, doxorubicin and cisplatin), CT showed widespread metastases in the retroperitoneum and he chose to receive the best supportive care. Aldosterone-producing adrenocortical carcinoma is exceedingly rare. To the best of our knowledge, only67 cases have been reported. Complete resection is needed to improve prognosis and this was not achieved in our case. We therefore recommend careful selection of the operative procedure.

Clinical practice pattern in patients with advanced urothelial cancer who had progressed on pembrolizumab in the pre-enfortumab vedotin era.

OBJECTIVES: Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment for advanced urothelial carcinoma. However, the standard treatment for patients after disease progression with pembrolizumab had not been established until the recent approval of enfortumab vedotin. We analyzed the treatment of these patients in the real world, and the patient background and outcomes. METHODS: We extracted data from 543 patients who experienced progressive disease after pembrolizumab initiation from a Japanese nation-wide cohort of platinum-refractory, metastatic urothelial carcinoma. RESULTS: The median overall survival of the 543 patients was 3.5 months (95% confidence interval 3.0-4.1). Of these, only 20.6% (n = 112) received chemotherapy as a subsequent systemic treatment after progressive disease. The regimen of chemotherapy was very diverse. The median overall survival was 11.9 months (95% confidence interval 9.2-14.7) for patients who received chemotherapy, compared to 2.4 months for those who did not receive chemotherapy (95% confidence interval 2.1-2.9; P < 0.0001). Patients who received subsequent chemotherapy were more likely to have better performance status, neutrophil-to-lymphocyte ratio <3, hemoglobin >11 mg/dL, and history of a single chemotherapeutic regimen at pembrolizumab initiation. CONCLUSIONS: This report highlights the real-world practice of the management after pembrolizumab treatment failure in the pre-enfortumab vedotin era, characterized by infrequent use of subsequent anticancer therapy comprising various regimens, reflecting the lack of a standard treatment. Clinical introduction of enfortumab vedotin is expected to improve treatment outcomes in this setting. The present study will provide important baseline data for evaluating the influence of enfortumab vedotin on clinical practices and outcomes.

[A Case of Bladder Plasmacytoma Diagnosed during Treatment of Multiple Myeloma].

A 78-year-old man was treated with Bortezomib, Lenalidomide, and Dexamethasone, for multiple myeloma. Two years after the start of treatment, the patient came to our department with a complaint of gross hematuria. Cystoscopy revealed a tumor on the left wall of the bladder. Urine cytology was negative. Magnetic resonance imaging (MRI) of the lower abdomen showed a slightly high signal on the T2-weighted image, indicating an intravesical mass lesion invading outside the bladder. Contrast-enhanced computed tomography (CT) also showed an intravesical mass and enlarged left external iliac lymph node swelling. Transurethral resection of bladder tumor was performed. The resection specimen showed tumor cells. The pathological examination revealed CD138 (+) and light-chain restriction. The patient was diagnosed with plasmacytoma. The patient was treated with radiation therapy for plasmacytoma of the bladder and surrounding lymph nodes, and then with daratumumab and dexamethasone for multiple myeloma for one year; however, the patient died because of worsening of multiple myeloma.

[A Case of Multiple Penile Schwannoma].

A 48-year-old man presented with a painless nodule on the right ventral aspect of the penile shaft root. The patient visited the hospital and complained that the mass was growing. On physical examinations, a 5 cm mass without tenderness was palpated. An isoechoic mass about 4 cm in size was observed on ultrasonography. Inhomogeneous high signal intensity was observed on T2-weighted magnetic resonance imaging. A needle biopsy revealed schwannoma. During surgery for excision of the tumor, another small tumor was detected both tumors were resected. Both tumors were diagnosed as schwannoma by pathological examination. Out of 40 cases of penile schwannoma reported, eight were of multiple tumors. In our case, it was difficult to detect the other small tumor by preoperative diagnosis. Therefore, we recommend careful observation during surgery.

[Clinical Course and Treatment of Acute Urinary Retention after Robot- Assisted Laparoscopic Radical Prostatectomy : A Single Institution Experience of 11 Cases].

Robot-assisted laparoscopic radical prostatectomy (RARP) is becoming the standard treatment procedure for localized prostate cancer. The main complications associated with RARP include urinary incontinence and sexual dysfunction. In addition, acute urinary retention (AUR) after urethral catheter removal is sometimes seen. Early catheter removal is a risk factor for AUR, and administration of alphablockers before catheter removal reduces the occurrence of AUR. However, the ideal management of AUR after RARP is not known. Here we report the clinical course and treatment after AUR. We performed 279 RARPs at our institution, and AUR developed in 11 cases. In all cases, urination status was improved after placement of a urinary catheter or intermittent catheterization. Later, urethral stricture was seen in 2 out of 11 cases. Ourstudy suggests that when AUR is observed afterRARP, catheterur ination should be initially performed. If urinary retention recurs, a urinary catheter should be placed with administration of alpha-blockers. The catheter is removed after about 3 days, and administration of analgesics is effective for reducing the pain on urination. If urination status is not improved, evaluation of the urethral stricture should be considered.

[A Case of Ureteral Metastasis from Prostate Cancer].

Ureteral metastasis from prostate cancer is rare. The present case report describes an 83-year-old patient with distant metastasis of prostate cancer to the right ureter that caused hydronephrosis. Upon initial examination at our hospital, he presented with a high prostate-specific antigen (PSA) level of 10.0 ng/ml. He was diagnosed with prostate adenocarcinoma, with Gleason score of 10 (5＋5) and clinical staging of cT2aN0M0. Intensity-modulated radiation therapy (IMRT) was performed after 1 year and 7 months of androgen depriation therapy. At 1 year and 4 months after IMRT, PSA increased to 3.068 ng/ml. Computed tomography scan revealed right hydronephrosis and thickening of the right ureter. We could not identify obvious malignant cells on ureteroscopic biopsy, and right nephroureterectomy was performed. Pathological examination revealed ureteral metastasis of prostate cancer. Six months after nephroureterectomy, PSA increased to 3.037 ng/ml. He was diagnosed with castration-resistant prostate cancer and has been treated with enzalutamide.

[A Case of Primary Renal Angiosarcoma with a Rapidly Worsening Course].

A 69-year-old man presented with left flank pain and underwent a computed tomographic scan, which revealed a large left renal mass of 16×9×5 cm. A left nephrectomy was performed. Pathological analysis revealed that the tumor was consistent with angiosarcoma of the left kidney with a negative surgical margin. He received combination therapy with radiation therapy and four courses of chemotherapy with doxorubicin and ifosfamide. However, he died 10 months after surgery because of pleural dissemination and peritoneal dissemination. Primary renal angiosarcoma is an extremely rare and highly aggressive tumor with a dismal survival rate, and a satisfactory surgical margin is necessary for its successful treatment. If primary renal angiosarcoma is suspected, biopsy may be considered before surgery. Primary renal angiosarcoma treatment with combination therapy of surgery, radiotherapy, and chemotherapy by a specialist multidisciplinary team with experience and expertise in sarcoma is preferable. Development of therapy for angiosarcoma is awaited.

The third national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from complicated urinary tract infection patients.

The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 µg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum ß-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.

Comparison of single- and multiple-dose cefazolin as prophylaxis for transurethral enucleation of prostate: A multicenter, prospective, randomized controlled trial by the Japanese Research Group for Urinary Tract Infection.

OBJECTIVES: To compare the optimal administration period of antimicrobial prophylaxis in patients undergoing transurethral enucleation of the prostate for benign prostatic hyperplasia. METHODS: We carried out a randomized controlled trial to compare the differences in incidence of perioperative genitourinary tract infection between single and multiple (3 days) administrations of cefazolin for transurethral enucleation of the prostate in benign prostatic hyperplasia patients without pyuria or bacteriuria between January 2015 and December 2018. RESULTS: This multicenter randomized controlled trial included 203 patients who underwent a transurethral enucleation of the prostate procedure. All received antimicrobial prophylaxis, and were randomized into those who received single-dose (n = 101) or multiple-dose (n = 102) therapy. The rate of genitourinary tract infection after transurethral enucleation of the prostate for all patients was 1.5%, whereas that in the single-dose group was 1.0% and in the multiple-dose group was 2.0%, which were not significantly different (P = 1.00). CONCLUSIONS: A single dose of antimicrobial prophylaxis as a prophylactic antibacterial drug is sufficient for patients undergoing transurethral enucleation of the prostate who do not have presurgical pyuria or bacteriuria.

[Radical Nephroureterectomy in Octogenarians].

We compared the perioperative and oncological outcomes of radical nephroureterectomy for renal pelvic and ureteral cancer between octogenarians and younger patients. We examined 146 patients attending our hospital from January 2012 to December 2019. The octogenarian group included 48 patients and the control group (younger patients) 98 patients. The median body mass index (BMI) (21.2 vs 23.4 kg/m^2, p<0.001), American Society of Anesthesiologists (ASA) score (p=0.044), preoperative albumin concentration (p=0.04) and operation time (287 vs 314 min, p=0.029) differed significantly between the two groups. However, there were no significant differences in perioperative complications between the two groups. According to multivariable analysis of overall survival, pT3 or higher pathology was a significant indicator of poor prognosis in all patients. In the octogenarian group alone, perioperative transfusion was the only other factor significantly associated with prognosis, whereas anti-CD55 monoclonal antibody (RM1) was a significant factor in the control group. There were significant differences between the octogenarian and control groups with respect to overall survival in those with pT2 or below stage disease (60.2% vs 87.5%, p=0.049), but not to cancer-specific survival (≤pT2 : 73.5% vs 94.2%, p=0.202 ≥pT3 : 72.2% vs 63.8%, p=0. 87). Our findings indicate that nephroureterectomy is a safe and efficient procedure for selected octogenarian patients.

[A Case of Isolated Peritoneal Metastasis from Prostate Cancer].

Peritoneal metastasis of prostate cancer is extremely rare, with only a few cases reported. A 78-yearold male patient was introduced to our hospital presenting with a prostate-specific antigen (PSA) level of 94.0 ng/ml at examination. He was diagnosed with poorly differentiated adenocarcinoma of the prostate, with a Gleasonscore of 9 (5＋4) at cT3bN0M0. Intensity-modulated radiation therapy was performed after 6 months of combined-androgen blockade (CAB) therapy. Twenty-one months later, several lymph node metastases were observed. With the resumptionof CAB therapy, PSA levels dropped and the multiple lymph node metastasis disappeared ; however, peritoneal metastasis was observed after 43 months. We performed a laparoscopic biopsy and our diagnosis after pathological evaluation was metastasis of the prostate cancer. He was treated with Enzalutamide.

[Distant Metastasis in Patients with Non-Muscle Invasive Bladder Cancer without Local Recurrence : Report of Two Rare Cases].

Distant metastasis is rare in patients with non-muscle invasive bladder cancer (NMIBC). We describe two cases of NMIBC with distant metastasis diagnosed in the follow-up period after transurethral resection (TUR), with neither intravesical recurrence nor progression to muscle-invasive disease. Case 1 : A 77-yearold man was referred to our hospital for treatment of a bladder tumor with the complaint of asymptomatic gross hematuria. TUR of the bladder tumor was performed. Pathological examination revealed high grade urothelial carcinoma pT1. Second TUR was performed and pathological examination confirmed high grade urothelial carcinoma pT1 with lymphovascular invasion. The patient received standard BCG therapy and subsequently developed left leg pain and lumbago 10 months after initial diagnosis. Magnetic resonance imaging, computed tomography, and bone scintigraphy demonstrated no local recurrence, but revealed multiple bone and liver metastases. The patient died 15 months after initial diagnosis. Case 2 : A 70-year-old man was referred to our hospital for treatment of an incidental bladder tumor. TUR of the bladder tumor was performed and pathological examination confirmed high grade urothelial carcinoma pT1. Second TUR was performed and pathological examination revealed no residual tumor cells. 18Fflurodeoxyglucose (FDG) positron emission tomography/computed tomography confirmed increasing uptake of 18F-FDG in the retroperitoneal lymph nodes, 18 months after initial diagnosis. The patient underwent laparoscopic lymphadenectomy. Pathological examination demonstrated metastasis of the bladder cancer. Combined chemotherapy was initiated with gemcitabine and cisplatin consecutively. To date the patient survives without progression or new distant metastases after four cycles of chemotherapy.

[Misdirection of an Indwelling Urethral Catheter into the Ureter in a Female Patient with Neurogenic Bladder : A Case Report].

We report a case of misdirection of an indwelling urethral catheter into the ureter. An 86-year-old women with neurogenic bladder had been undergoing chronic indwelling urethral catheter exchange for 1 year. She was referred to our hospital owing to lower abdominal pain and gross hematuria. A computed tomographic scan showed an indwelling urethral catheter in the right ureter. Retrograde ureterography showed that the ureter had no leakage and the catheter was removed under fluoroscopic guidance. Urethral catheterization is a common procedure. We reviewed 23 cases of an indwelling urethral catheter entering the ureter and we consider that this misdirection occurs particularly among female patients with neurogenic bladder.

[Two Cases of Inflammatory Myofibroblastic Tumor of the Urinary Bladder].

We describe two cases of inflammatory myofibroblastic tumor (IMT) of the urinary bladder. Case 1 : A 55-year-old man complained of urinary frequency. Transurethral biopsy of the bladder tumor was performed ; pathological examination revealed IMT. After steroid therapy for 1 year, the tumor was markedly reduced in size. Laparoscopic partial cystectomy was performed. The patient has now been free from recurrence for 3 years after the surgery. Case 2 : A 61-year-old man presented with gross hematuria. Transurethral biopsy of the bladder tumor revealed IMT. Despite steroid therapy for 6 months, the tumor size increased. Laparoscopic partial cystectomy and vesicoureteroneostomy were performed. The patient has now been free from recurrence for 1 year and 11 months after the surgery. IMT of the urinary bladder often responds well to steroid therapy. We experienced two cases of IMT. One showed a good response to steroid therapy and the other showed a poor response to steroid therapy. In both cases, we performed laparoscopic partial cyctectomy and the patients have remained free from recurrence IMT of the urinary bladder may have a good prognosis after complete surgical resection.

[Lymph Node Metastasis to the Prostatic Anterior Fat Pad in the Patients Treated with Prostatectomy].

We investigated the prostatic anterior fat pad (PAFP) for the presence of lymph nodes and lymph node metastases after excision during radical prostatectomy for the treatment of prostate cancer. From November 2013 to May 2017, 215 patients underwent radical prostatectomy for localized prostate cancer at our institution. PAFP was removed and sent for pathological analysis routinely to evaluate the presence of lymph nodes and lymph node metastases. Of the 215 patients, 20 (9.3%) had lymph nodes in the PAFP. Among the 20 patients with lymph nodes in the PAFP, 2 patients (10.0% ; 0.9% of all patients) were positive for metastatic prostate cancer. These patients did not have positive nodes elsewhere among the pelvic lymph nodes. There was no significant difference in the clinicopathological features between the patients with lymph nodes in the PAFP and those with no lymph nodes in the PAFP. The present findings are similar to those in the Western population. Considering the very low rate of lymph node metastasis in PAFP, it is necessary to discuss which patients should be selected for pathological analysis of PAFP.

[A Case of Primary Sigmoid Colon Lymphoma Presenting with Sigmoidovesical Fistula in a Patient with a Long History of Ulcerative Colitis].

A 73-year-old male patient with a 16-year history of ulcerative colitis presented to our hospital with a history of pneumaturia and fever. Cystoscopy and a computed tomography scan showed sigmoidovesical fistula. Colonoscopy showed a necrotic tumor along with sigmoidovesical fistula. A biopsy was not sufficient to make a definitive diagnosis of the tumor. Total colectomy with ileostomy and partial cystectomy were performed. A pathological examination showed diffuse large B-cell lymphoma of the sigmoid colon. On postoperative day 35, delayed dehiscence of the bladder wall was detected and a biopsy of the bladder wall showed lymphoma. Standard systemic chemotherapy (R-THP-COP) was administered and the defect of the bladder was closed. Three years and 2 months postoperatively, the patient has no local recurrence or distant metastasis.

[An Increase in Cases of Bladder Tamponade Due to Cystitis Among Elderly Women and Clinical Background Factors].

Bladder tamponade is thought to be caused mainly by bladder cancer or radiation cystitis. However, in women, it may often be caused by cystitis in clinical settings. This has not been noted in previous reports of bladder tamponade in Japan. Thus, we retrospectively analyzed the clinical features of 83 male and 41 female patients with bladder tamponade. Seventy-four patients were treated at Nishi-Kobe Medical Center between April 2005 and March 2015, and 50 were treated at Shizuoka City Shizuoka Hospital between November 2008 and March 2015. The patients'median age was 80 years. The cause of bladder tamponade was urological malignancies in 33 of the 83 male patients (40%), benign prostatic hyperplasia in 20 of the 83 male patients (24%), and cystitis in 33 of the 41 female patients (80%). Compared with the men, the women with bladder tamponade were significantly older and the proportion of patients with cerebrovascular disease, diabetes, and dementia was higher. In addition, more women were nursing home residents, with a higher rate of voiding with diapers and antithrombotic use than men. Causative strains of cystitis were diverse, and some were antibiotic resistant. Most of the cases of bladder tamponade in the women occurred in the elderly and were caused by cystitis. In an aging society, increases in the incidences of chronic, complicated cystitis due to impaired independent micturition, dysuria, and systemic diseases such as diabetes, and increased use of antithrombotic drugs may contribute to bladder tamponade in women.