Comparisons of in-hospital fee and surgical outcomes between robot-assisted, laparoscopic, and open radical cystectomy: a Japanese nationwide study.

OBJECTIVE: To evaluate in-hospital fees and surgical outcomes of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) using a Japanese nationwide database. METHODS: All data were obtained from the Diagnosis Procedure Combination database between April 2020 and March 2022. Basic characteristics and perioperative indicators, including in-hospital fees, were compared among the RARC, LRC and ORC groups. Propensity score-matched comparisons were performed to assess the differences between RARC and ORC. RESULTS: During the study period, 2931, 1311 and 2435 cases of RARC, LRC and ORC were identified, respectively. The RARC group had the lowest in-hospital fee (median: 2.38 million yen), the shortest hospital stay (26 days) and the lowest blood transfusion rate (29.5%), as well as the lowest complication rate (20.9%), despite having the longest anesthesia time (569 min) among the three groups (all P < 0.01). The outcomes of LRC were comparable with those of RARC, and the differences in these indicators between the RARC and ORC groups were greater than those between the RARC and LRC groups. In propensity score-matched comparisons between the RARC and ORC groups, the differences in the indicators remained significant (all P < 0.01), with an ~50 000 yen difference in in-hospital fees. CONCLUSIONS: RARC and LRC were considered to be more cost-effective surgeries than ORC due to their superior surgical outcomes and comparable surgical fees in Japan. The widespread adoption of RARC and LRC is expected to bring economic benefits to Japanese society.

Differential treatment responses to immune checkpoint inhibitor (ICI) therapy in a case of multiple primary malignancies: the programmed death ligand-1 (PD-L1) negative ureteral and lung metastasis from a clear cell renal cell carcinoma appearing after robotic-assisted partial nephrectomy progressed after ICI therapy, while synchronous PD-L1-positive primary lung squamous cell carcinoma responded very well to ICI therapy: a case report.

BACKGROUND: Renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are representative malignancies that respond well to immune checkpoint inhibitors (ICIs). Research has been conducted to identify biomarkers, such as programmed death ligand-1 (PD-L1), that would allow the response to ICI therapy to be predicted; however, the complex tumor immune system consisting of both host and tumor factors may also exert an influence. CASE PRESENTATION: Computed tomographic imaging (CT) incidentally revealed a left renal mass, and a left pulmonary nodule with multiple lymph node metastases (LNMs). Firstly, video-assisted thoracic surgery revealed a lung tumor invading the chest wall. Histologically, the findings of the tumor were consistent with squamous cell carcinoma (SCC), and immunohistochemistry (IHC) showed positive PD-L1 expression. The renal tumor was excised by robotic-assisted partial nephrectomy (RAPN). Histologically, the renal tumor showed the features of clear cell carcinoma (CCC). Four months after the RAPN, CT revealed left hydronephrosis caused by an enhancing ureteral tumor. Then, multiple right lung metastases appeared, and the left lung tumor increased. Following treatment including atezolizumab, the primary lung SCC and the multiple LNMs almost disappeared completely, while the ureteral and right lung metastases showed progression. The ureteral metastasis was resected by left open nephroureterectomy. Histology of the ureteral tumor revealed features consistent with CCC. Histological examination of the multiple right lung metastases that were resected by partial lobectomy via a small thoracic incision also revealed features consistent with CCC. Two months after nephroureterectomy, a solitary left lung metastasis was treated by nivolumab and ipilimumab. Six months after nephroureterectomy, the patient died of RCC. Further studies of specimens revealed that the tumor cells in the primary RCC and the ureteral and lung metastases showed negative results of IHC for PD-L1. CONCLUSIONS: The responses to ICI therapy of concomitant RCC and NSCLC were quite different. The PD-L1 expression status in individual tumors in cases of multiple primary malignancies (MPMs) may directly predict the response of each malignancy to ICI therapy, because the host immune system, which may affect the response to ICI therapy, could be the same in MPMs.

CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis.

CD169+ macrophages are suggested to play a pivotal role in establishing anti-tumor immunity. They capture dead tumor cell-associated antigens and transfer their information to lymphocsytes, including CD8+ T cells, which is important for successful tumor suppression. This study aimed to determine the prognostic significance of CD169+ macrophages residing in the tumor-draining lymph nodes from cases of bladder cancer. In this retrospective study, 44 bladder cancer patients who received radical cystectomy were examined. The abundance of CD169+ macrophages in the regional lymph nodes and the number of CD8+ T cells in the primary tumor were investigated by immunohistochemistry. A CD169 score was calculated based on the intensity of CD169 staining and the proportion of CD169+ macrophages, and the scores were compared to the patients' clinicopathological parameters. A high CD169 score was significantly associated with low T stage and with a high number of CD8+ T cells infiltrating into the tumor. The group with high CD169 expression had significantly longer cancer-specific survival than the group with low CD169 expression (5-year cancer-specific survival rate: 83.3% vs 31.3%). In a multivariate analysis, the CD169 score was identified as a strong and independent favorable prognostic factor for cancer-specific survival. Our findings suggest that CD169+ macrophages in the lymph nodes enhance anti-tumor immunity by expanding CD8+ T cells in bladder cancer. The CD169 score may serve as a novel marker for the evaluation of bladder cancer prognosis.

CD169+ Macrophages Residing in the Draining Lymph Nodes and Infiltrating the Tumor Play Opposite Roles in the Pathogenesis of Bladder Cancer.

Purpose: CD169+ macrophages are considered to enhance anti-tumor immunity by capturing lymph-borne dead tumor cells. The number of CD169+ macrophages in regional lymph nodes (RLNs) is positively correlated with prolonged cancer-free survival in various human cancers. However, a recent study argued against this dogma; that is, CD169+ macrophages infiltrating into the tumor were associated with poor prognosis in patients with breast cancer. To explain this discrepancy, we quantified the number of CD169+ macrophages located in the bladder tumor and RLNs of the same patients and examined their relationship with the 5-year survival rate. Patients and Methods: Tumor and RLN specimens resected from 40 invasive bladder cancer patients (29 males and 11 females; median age, 70.7 years; range, 49-81 years) who underwent radical cystectomy were evaluated using immunostaining. Results: The number of CD169+ macrophages in RLNs was associated with a good cancer prognosis, while CD169+ macrophages infiltrating the tumor strongly correlated with a higher incidence of lymphovascular invasion. Conclusion: CD169+ macrophages play opposing roles in the induction of anti-tumor immunity based on their location in RLNs or tumors.

Gradual resolution over time of recurrent dystrophic calcification after bipolar transurethral resection of the prostate: A case report.

Dystrophic calcification (DC) after transurethral resection of prostate (TURP) is rare. In our patient, bipolar TURP was performed by an experienced urologist, without complications. Seven months later, he developed a tingling urethral sensation, difficulty in urination, urgency, and perineal discomfort. Computed tomography (CT) showed a high-density area occupying the prostatic resection cavity. Re-surgery involved laser ablation of the DC. Two months later, the DC recurred. At the second re-surgery, the DC was removed without using electricity. Repeat CT at 13 months showed near complete disappearance of the DC. Wound healing might interrupt the vicious cycle of DC recurrence.

Intranodal glue embolization for lymphorrhea following inguinal lymphadenectomy in penile cancer: A case report.

An 86-year-old man underwent total penectomy and bilateral inguinal lymphadenectomy (ILND) for penile cancer with an enlarged right inguinal lymph node. The accumulation of 100-150 ml of lymphatic fluid was observed in the right inguinal drain in a day after surgery. Compression was performed, without any improvement in lymphorrhea. During the right inguinal lymphangiography performed on postoperative day (POD) 28, lymphorrhea was still detected. Lymphorrhea was improved 2 days after intranodal glue embolization (IGE) was performed using a mixture of lipiodol and n-butyl-2 cyanoacrylate (NBCA). IGE was effective for intractable lymphorrhea after ILND in penile cancer.

Development of a Humanoid Hand System to Support Robotic Urological Surgery.

In robotic urological surgery, it is common for an assistant to use laparoscopic forceps to move organs clear of the surgical working space; however, the assistance efficiency is low. In this study, we aimed to develop a three-fingered humanoid hand with multiple degrees of freedom and a folding mechanism that would allow it to be inserted through a small incision to improve the efficiency of assisting with organs. The bladder (with prostate) and kidneys were selected as the target organs. To achieve stable assistance for these organs, we analyzed three postures: "grasp," "open palm," and "pinch." We verified that the proposed hand can be inserted into the abdominal cavity through a 20 mm port and can assist in a grasping an object of the same size as the target organ with these three movements. Clinical Relevance- The proposed three-fingered, eight-degree-of-freedom humanoid hand with a folding mechanism can be inserted through a 20-mm port and is shown to be able to stably assist in grasping objects of the same size as the kidney and bladder (with prostate) in the urological surgical workspace.

Bladder metastasis with additional metastases in multiple other organs 4 years after radical nephrectomy for clear cell renal cell carcinoma: a case report and review of the literature.

BACKGROUND: Renal cell carcinoma rarely metastasizes to the bladder, and its biological behavior is not yet fully understood. CASE PRESENTATION: In our case (54-year-old Japanese woman), computed tomography evaluation suggested the presence of a bladder metastasis, associated with additional metastases in the lungs, mediastinal lymph nodes, ribs, and renal bed, 4 years after radical nephrectomy for renal cell carcinoma. The histological findings of the metastatic bladder tumor were consistent with those of clear cell carcinoma. The mediastinal lymph node, rib, and renal bed metastases responded to treatment with an immune checkpoint inhibitor administered for 12 months after surgery for the bladder and lung metastases. In patients with bladder metastasis, absence of metastases in other organs and an interval of more than 1 year after nephrectomy are known to be favorable prognostic factors. Interestingly, in our case, the bladder metastasis was detected more than 1 year after nephrectomy, which was a favorable factor, but there were also metastases in other organs, which was an unfavorable factor. Therefore, we reviewed the literature, including that pertaining to targeted therapy and immune checkpoint inhibitor therapy published in the last two decades, to analyze the clinical significance of the presence of additional metastasis in other organs in renal cell carcinoma (clear cell type, which is the predominant subtype) patients with bladder metastasis. CONCLUSIONS: Patients with bladder metastasis after nephrectomy for renal cell carcinoma also having metastases in other organs may respond to targeted therapy and immune checkpoint inhibitor therapy. This may suggest that the interval to relapse in the bladder after nephrectomy may be a more important prognostic factor than the presence of synchronous metastases in other organs.

Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice.

Phospholipid hydroperoxide glutathione peroxidase (GPx4) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids. GPx4 is strongly expressed in the mitochondria of testis and spermatozoa. We previously found a significant decrease in the expression of GPx4 in spermatozoa from 30% of infertile human males diagnosed with oligoasthenozoospermia (Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M., and Nakagawa, Y. (2001) Biol. Reprod. 64, 674-683). To clarify whether defective GPx4 in spermatocytes causes male infertility, we established spermatocyte-specific GPx4 knock-out mice using a Cre-loxP system. All the spermatocyte-specific GPx4 knock-out male mice were found to be infertile despite normal plug formation after mating and displayed a significant decrease in the number of spermatozoa. Isolated epididymal GPx4-null spermatozoa could not fertilize oocytes in vitro. These spermatozoa showed significant reductions of forward motility and the mitochondrial membrane potential. These impairments were accompanied by the structural abnormality, such as a hairpin-like flagella bend at the midpiece and swelling of mitochondria in the spermatozoa. These results demonstrate that the depletion of GPx4 in spermatocytes causes severe abnormalities in spermatozoa. This may be one of the causes of male infertility in mice and humans.

Clinical efficacy of naftopidil on lower urinary tract symptoms after radical prostatectomy.

OBJECTIVE: The management of lower urinary tract symptoms that persist after radical prostatectomy remains to be established. We investigated whether an alpha1-blocker, naftopidil, improves LUTS in patients >or=1 year after radical prostatectomy. METHODS: A total of 29 male patients received 25 mg/day of naftopidil for the first week, then 75 mg/day for 4 weeks. The frequency-volume chart, international prostate symptom score and quality of life index (QOL) were examined before and at the end of the 5-week administration in all subjects. RESULTS: Total international prostate symptom score (I-PSS) and I-PSS subtotals associated with voiding symptoms and storage symptoms were significantly decreased at 5 weeks compared with baseline (P < 0.001 each). QOL index was significantly improved with naftopidil for 5 weeks (P < 0.001). From analyses of the frequency-volume chart, mean and maximum volume/void were significantly increased (P < 0.05 each). CONCLUSION: Lower urinary tract symptoms detected in patients >or=1 year after radical prostatectomy were markedly improved with administration of naftopidil at 75 mg/day. These symptoms could represent a novel target for medical treatment by improved understanding of the symptom pathology in the near future.

[A case of non-traumatic rupture of varicocele].

We report a case of a non-traumatic rupture of varicocele. A 28-year-old man visited our hospital complaining of left scrotal swelling with severe spontaneous pain of sudden onset after straining for defecation. MRI revealed a dilated spermatic cord with scrotal hematoma surrounding the left testis, which leads to the diagnosis of varicocele rupture. Conservative treatment with oral analgesics for a couple of weeks relieved the swelling and pain. Subinguinal microscopic ligation of left spermatic veins was performed 4 months later.

[5 years intravesical instillation with mitomycin-C and pirarubicin as a prophylactic treatment for superficial bladder cancer].

PURPOSE: We studied prophylactic intravesical instillation of mitomycin C (MMC) and pirarubicin (THP) following transurethral resection of bladder tumor (TUR-Bt) for superficial bladder cancer. MATERIALS AND METHODS: Forty-six evaluable patients were administered intravesically 20 mg of MMC dissolved in 20 ml saline on day 1 and 20 mg of THP dissolved 20 ml 5% dextrose on day 2. The patients were followed up by cystscopy and urinary cytology. Intravesical instillations were performed once a month and continued for 5 years. RESULTS: The non-recurrence rates at 1, 3 and 5 years were 88.8%, 79.5% and 67.0%, respectively. No significant differences were observed between grade 1-2 and 3, male and female, and solitary and multiple tumors. Although the side effects were relatively mild, 6 patients were stopped intravesical instillation. CONCLUSIONS: Because non-recurrence rates of our report is not better than previous reports with shorter treatment periods, intravesical MMC and THP instillation for 5 years is not beneficial to the patients with superficial bladder cancer.

[Bone loss in men under androgen-deprivation therapy for prostate cancer].

Bone is a major target tissue for sex hormones and hypogonadism is a known cause of male osteoporosis. Androgen-deprivation therapy (ADT) for prostate cancer yields hypogonadotropic status and accelerates age-related decrease in bone mineral density. The risk for osteoporotic fractures is also increased which may lead to a shorter life expectancy for prostatic cancer patients. Baseline and follow up bone density measurement is desired for all men beginning ADT and it is advisable to take calcium and vitamin D as well as maintain a moderate exercise. Bisphosphonate is a possible treatment for those in whom osteoporosis develops. More data are desirable to make a guideline to prevent and treat male osteoporosis under ADT.

Bone mineral density in hypogonadal men remains low after long-term testosterone replacement.

AIM: In 11 congenital hypogonadal men, the bone mineral density (BMD) values were determined to assess the effect of long-term androgen replacement therapy (ART) on skeletal integrity. METHODS: Eleven congenital hypogonadal men, including 8 isolated gonadotropin deficiency patients, 2 Kallmann's syndrome and 1 vanishing testes syndrome were recruited and treated with 250 mg of testosterone enanthate intramuscularly every 4 weeks for 7-43 years (mean+/-SD: 21.5 +/-13 years). In these patients and a group of 10 healthy young men (controls), the whole and trabecular BMDs were examined at the distal end of radius by means of a peripheral quantitative computerized tomography device. RESULTS: The whole radial BMD in hypogonadal men was significantly less in the patients than in the healthy men (498+/-115 and 725+/-134 mg/cm(3), respectively; P<0.01); the trabecular BMD was also lower in the hypogonadal men (199+/-80 and 375+/-89 mg/cm(3); P< 0.01). The whole radial BMD values in 10 of 11 hypogonadal men were at least 1 SD below the mean value for healthy young men; 2 hypogonadal men had BMD values more than 2.5 SD lower than the healthy mean. Additionally, the whole radial BMD showed a significant negative correlation with the patient's age at the initiation of ART (r = 0.748, P<0.01). The serum level of bone-specific alkaline phosphatase and the urinary level of deoxypyridinoline were not significantly different between the two groups. CONCLUSION: Osteopenia persists in the hypogonadal men after long-term ART, suggesting that such patients have a persistent defect in bone development not alleviated by androgen replacement.

[A case of non-functioning adrenocortical adenoma associated with renal cell carcinoma].

Left renal and left adrenal masses were incidentally found by computerized tomography (CT) in a 56-year-old man who was admitted to our hospital for treatment of upper digestive tract hemorrhage. Apparently no clinical signs suggestive of Cushing's syndrome existed. The renal tumor was diagnosed as renal cell carcinoma based on the findings on enhanced CT. 131I-adosterol uptake in the examination of adrenal scintigraphy under dexamethasone suppression was definitely increased in the left adrenal gland, although hormonal examinations of serum and urine for adrenal functions were within the normal range. Plasma adrenocorticotropic hormone (ACTH) and serum cortisol were suppressed by administration of 2 mg dexamethasone for 2 days. The left kidney was radically removed by surgery together with the left adrenal gland. Histological diagnoses were left renal cell carcinoma and adrenocortical adenoma.

[Transitional cell carcinoma of the urinary bladder accompanied by signet-ring cell carcinoma: a case report].

A 58-year-old man visited our clinic with complaints of gross hematuria and pollakisuria. Cystoscopic examination revealed multiple non-papillary broad based tumors and reddish unstable mucosa in the bladder. The pathological specimen of the transurethral biopsy of the tumors showed signet-ring cell carcinoma predominantly and adenocarcinoma transforming into signet-ring cell carcinoma partially. A total cystectomy with ileal conduit urinary diversion was performed. The histopathological finding of the radical cystectomy specimen was grade 3 transitional cell carcinoma accompanied by adenocarcinoma. These findings suggest that the adenomatous metaplasia of transitional cell carcinoma in the bladder could differentiate into signet-ring cell carcinoma.

[Long-term survival in patients with metastatic renal cell carcinoma managed with conservative therapy: a report of two cases].

Case 1. A 58-year-old man underwent radical nephrectomy due to a tumor in the left kidney (renal cell carcinoma, clear cell subtype, G3, pT1bpN0) in 1988. Thirteen years later, he underwent surgical resection of metastases to lung and cerebrum and gamma ray knife resection of two other sites of metastases to cerebrum in 2001. He had no evidence of disease in April, 2003. Case 2. A 53-year-old man underwent radical nephrectomy due to a tumor in the right kidney (renal cell carcinoma, clear cell type, pT1apN0) in 1987. From 1996 to 2001, irradiation therapy to multiple metastases to thoracic vertebrae (50 Gy), rib (50 Gy), para-aorta lymph nodes (40 Gy), sacrum (44 Gy) and sternum (44 Gy), and surgical resection of dermal metastasis were performed. Paraplegia occurred due to regrowth of thoracic bone metastasis in December, 2001. In February, 2002, he died of septic shock caused by infection of decubitus. Surgical resection and palliative therapy of recurrent metastatic foci was useful to improve the quality of life and probably prognosis.

[Fibroepithelial polyp of the anterior urethra, found during post-operative follow-up of ureteral cancer].

A 52-year-old man underwent nephroureterectomy against left distal ureteral cancer (transitional cell carcinoma, Grade 2, pTa), and was followed up by surveillance alone. Twenty-two months postoperatively, a pedunculated tumor was found in the anterior urethra by cystourethroscopy. Pathological examination of the tumor resected transurethrally revealed a fibroepithelial polyp. There have been only twelve cases of fibroepithelial polyp of the anterior urethra reported in the literature. Since 4 out of 8 adult cases among them were found during the postoperative follow up period of urothelial cancer, mechanical irritation by repeated transurethral procedures might be responsible for the development of fibroepithelial polyp of the anterior urethra in these cases. If anterior urethral tumor is found during follow-up urothelial carcinoma, benign urethral polyp should be considered in the differential diagnosis.

[A case of giant perineal epidermal cyst: a case report].

A 33-year-old man was admitted to our hospital with the chief complaint of a giant perineal mass causing difficulty in walking. Magnetic resonance imaging revealed cystic tumor with a diameter of 13 cm. We performed tumor resection. Histopathological diagnosis of the tumor was epidermal cyst. To our knowledge, this is the sixth case of perineal epidermal cyst reported in Japan.

[Alveolar rhabdomyosarcoma originating in spermatic cord: a case report].

A 19-year-old man visited our hospital complaining of swelling of the left inguinal region. A thumb head-sized tumor was palpated through the skin on the left spermatic cord. Tumor resection was performed because it was dissected easily apart from the left spermatic cord. Pathological examination revealed alveolar rhabdomyosarcoma with positive surgical margin. Computed tomographic scanning revealed no retroperitoneal lymph node swelling, and there were no clinical findings of distant metastasis (clinical stage I). Radical inguinal orchiectomy with combined chemotherapy using vincristine, dactinomycin, and ifosfamide (VAI) was performed. He has been alive without any recurrence for 8 years and 8 months after the surgery.