Prognosis of Patients Receiving Chemotherapy for Metastatic Upper Tract Urothelial Carcinoma Compared With Metastatic Urinary Bladder Cancer.

BACKGROUND/AIM: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. RESULTS: The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. CONCLUSION: Platinum-based chemotherapy had a similar effect on patients with mUTUC and mUBC.

Current status and future perspectives of the managements of metastatic hormone-sensitive prostate cancer.

PURPOSE: The therapeutic landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has changed dramatically. Here, we provide the current status and future prospective of the management of mHSPC. METHODS: We reviewed recent literature of landmark studies on the managements of mHSPC. RESULTS: Upfront docetaxel or androgen receptor signaling inhibitor (ARSi) in addition to ADT has improved survival in mHSPC patients and has become the new standard of care. Triplet therapy with docetaxel, ARSi and ADT also improved survival. In the future, triplet therapy may become the standard of care. Oligometastatic mHSPC patients could benefit from local therapy. The inclusion of risk factors or the genetic biomarkers will provide the best treatment for individual mHSPC patients. CONCLUSION: Strong systemic therapy in the first-line treatment of mHSPC has been shown to improve survival and quality of life. Currently, several clinical trials are evaluating novel compounds such as PARP inhibitor, AKT inhibitor, and immune checkpoint inhibitor. The therapeutic landscape of mHSPC management will change dramatically.

Comparison of Abiraterone and Combined Androgen Blockade Therapy for High-Risk Metastatic Hormone-Sensitive Prostate Cancer: A Propensity Score-Matched Analysis.

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score-matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2-89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.

[A CASE OF UNRESECTABLE METASTATIC RENAL CARCINOMA SUCCESSFULLY TREATED BY COMBINED MODALITY THERAPY WITH NIVOLUMAB AND SURGERY].

The patient was a 65-year-old male who was referred with right renal mass (8 × 6.7 cm) and swelling of para-aortic lymph nodes in CT in April, 20XX. Additional examinations revealed inferior vena cava invasion, multiple lung metastases and left iliac bone metastasis and he was diagnosed with a renal cell carcinoma (cT4N1M1b). Pazopanib was administered as the first line treatment for an unresectable renal cancer. Nivolumab was then administrated as the 2nd line therapy due to the disease progression evaluated in (late) June, 20XX. However, immediately after the first administration of nivolumab, the patient have a difficulty in walking resulting from low-back pain, and MRI showed multiple lumbar vertebral metastases and L2 compression fracture. He was transferred to another hospital for combined modality therapy including right femoral head replacement and palliative radiotherapy in August, 20XX. Nivolumab was resumed since he had stable disease after his return to our hospital, and a total of 20 cycles of nivolumab treatment was performed. A follow-up CT showed 70% decrease in an initial primary tumor and tumor decrease or disappear in metastatic lung and bone tumors. The primary tumor was considered surgically resectable, and a radical nephrectomy was performed in August 20XX +1. Histopathological examination showed with a marked effect of neoadjuvant therapy and no evidence of viable tumor cells. We report a case of unresectable carcinoma that was successfully treated with nivolumab.

The Change in Neutrophil Lymphocyte Ratio from the First to the Last Repeat Prostate Biopsy Proposed as a Marker of Carcinogenesis.

INTRODUCTION: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (ΔNLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. MATERIALS AND METHODS: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy, ΔNLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. RESULTS: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters, ΔNLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. CONCLUSIONS: ΔNLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa.

Efficacy of Adding Dutasteride to α-Blocker Therapy Treated Benign Prostatic Hyperplasia Patients with Small Volume Prostate (<30 mL).

OBJECTIVES: To assess the efficacy of dutasteride add-on therapy for patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with small prostates who have been treated with α-blocker therapy for >3 months. METHODS: A total of 110 men with clinical BPH were enrolled. There were 17 and 93 subjects with a prostate volume (PV) <30 and ≥30 mL, respectively. All subjects had been treated with α-blocker therapy for >3 months. Subjective and objective clinical variables were assessed using the total International Prostate Symptom Score (IPSS-T), IPSS quality of life (IPSS-QoL), IPSS voiding subscore (IPSS-V), IPSS storage subscore (IPSS-S), overactive bladder symptom score (OABSS), PV, prostate specific antigen (PSA) level, post-void residual (PVR), and maximum flow rate (Qmax). These variables were assessed at baseline and every 3 months for 1 year. RESULTS: In the small prostate group, IPSS-T and IPSS-V showed improvements from baseline at 6 and 9 months, storage subscore at 6 months, and OABSS at 3 months, but no sustained improvements were observed. During the study period, only the IPSS QoL scores did not show any improvement. Conversly, dutasteride was significantly effective at improving IPSS-T, IPSS-V, IPSS-S, and IPSS-QoL scores throughout the study period in the large prostate BPH group. PSA levels and PV significantly decreased in both groups throughout the study. CONCLUSIONS: Benign prostatic hyperplasia in LUTS patients with small prostates did not show a sustainable benefit from the addition of dutasteride to α-blocker therapy.

[A CASE OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER WITH SQUAMOUS DIFFERENTIATION RESPONDING TO PACLITAXEL AND CARBOPLATIN NEOADJUVANT CHEMOTHERAPY].

A 42-year-old man was referred to our hospital for macrohematuria. Computer tomography and magnetic resonance imaging revealed right hydronephrosis and a retroperitoneal mass, located next to right side of the bladder. Cystoscopy showed a protruded lesion covered with normal mucosa at the right lateral wall. The patient underwent transurethral resection of the bladder tumor and biopsies of the bladder wall. Histological examination showed squamous cell carcinoma. Neoadjuvant chemotherapy using paclitaxel and carboplatin (TC) was performed. A total cystectomy, right nephroureterectomy and construction of the ileal conduit were performed after one course of systemic chemotherapy. Histological examination showed urothelial carcinoma with squamous cell differentiation. Unexpectedly, a small amount of CIS was detected only in the vicinity of the TUR scar. The patient received 2 cycles of TC chemotherapy as adjuvant chemotherapy. Unfortunately, 11 months later, local recurrence and liver metastasis were detected. He died 17 months after the surgery.

Clinical Outcome of Small Renal Cell Carcinoma after Delayed Surgery versus Immediate Surgery.

BACKGROUND: This study was undertaken to investigate the growth rate and clinical outcome of patients with a small renal mass (SRM) after delayed surgery versus immediate surgery. METHODS: We reviewed the clinical records of 328 patients with SRM ≦ 4cm at diagnosis, who underwent delayed or immediate surgical intervention from January 2000 to December 2011. Radiographic evaluation using CT scan and MRI were performed at least every 6 months and the tumor size was determined at least twice in the delayed surgery group. RESULTS: A total of 292 RCC patients with pT1aN0M0 were identified; among them, 32 patients had been managed with delayed surgery intervention. No statistically significant difference was observed in overall survival rate (OSR) and cancer recurrence-free rate (CRFR). But cancer-specific survival rate (CSSR) was significantly lower in the delayed surgery group (p=0.0002). CONCLUSIONS: The overall survival rate of delayed surgery was not inferior compared with that after immediate surgery. Delayed surgery intervention for SRMs is a treatment option in the current study.

[Spontaneous renal artery dissection with renal infarction: a case report].

A 58-year-old woman visited our hospital with nausea and right flank pain. At first abdominal ultrasonography was performed, suggesting a right renal infarction. Computed tomography (CT) study of the abdomen with intravenous contrast was performed to determine the cause of the symptoms. The scan revealed poor enhancement in the lower half of the right kidney. She was diagnosed with a right renal infarction. She was initially treated with anticoagulant therapy, but 5 days later, she complained of nausea. This time, CT demonstrated exacerbation of a right renal infarction with renal artery dissection. Based on this finding, we performed a right nephrectomy. The result of pathology was segmental arterial mediolysis. She was discharged 12 days after the surgery and is doing well at 6 months after discharge. Spontaneous renal artery dissection is a rare disease. It constitutes approximately 0.05% of arteriographic dissections. In addition, spontaneous renal artery dissection shows nonspecific symptoms. Together, these two factors may cause a delay in diagnosis.

Micropapillary urothelial carcinoma of the renal pelvis: report of a case and review of the literature.

BACKGROUND: Micropapillary urothelial carcinoma (MPUC) is a rare variant of urothelial carcinoma (UC), which is often advanced at presentation, and carries poor prognosis. Majority of the reported cases of MPUC originate from the urinary bladder. Of over 190 MPUC cases reported in the English literature, 35 cases were of the upper urinary tract. We report a rare case of MPUC of the renal pelvis. CASE REPORT: A 73-year old woman presented with hematuria. She had a mass in the left renal pelvis with massive infiltration in the renal parenchyma. She underwent surgery. Pathological stage was pT4N2M1. Although she received chemotherapy, she died of disease 14 months after operation. Histologically, MPUC was found in 40% of the tumor, mostly in the infiltrating portion. Immunohistochemically, MPUC showed intracytoplasmic expression of CK7 and CK20. Distinctive expression of MUC1 was observed on the stroma-forming surface of the neoplastic clusters in MPUC. Positive staining for p53 and negative staining for bcl-2 were remarkable. In the review of the literature, overall male predominance was remarkable (M:F=5.09:1), but it was less pronounced in the upper urinary tract (M:F=1.61:1). CONCLUSIONS: Here we present a rare case of MPUC arising in the renal pelvis with thorough review of the literature.

[Pulmonary metastasis of renal cell carcinoma 20 years after nephrectomy].

A 70-year-old man underwent right nephrectomy for clear cell renal carcinoma in 1985. After nephrectomy, he was routinely followed up as an outpatient. Solitary chest tumor was detected on pulmonary CT in 2005. A wedge resection of pulmonary tumor was performed under diagnosis of primary lung cancer. The histological feature was not of primary lung cancer, but the previous nephrectomised specimen, i.e., clear cell renal carcinoma.

Both T and non-T cells with proliferating potentials are effective in inducing suppression of allograft responses by alloantigen-specific intravenous presensitization combined with suboptimal doses of 15-deoxyspergualin.

In an MHC class I-disparate combination of mouse strains, a single intravenous injection of donor spleen cells combined with 10 suboptimal doses of 15-deoxyspergualin (DSG) administration was effective in inducing donor-specific suppression of cytotoxic T-lymphocyte (CTL) responses and prolonged survival of the relevant skin allograft. Proliferative potentials of the donor spleen cells were requirement for the induction of suppressed allospecific responses, but both highly purified T cells and non-T cells were equally effective to induce the suppression of CTL responses by intravenous injection. These results have shown that, although working on different mechanisms, DSG is as effective as FK506 or rapamycin in inducing allograft tolerance when used at suboptimal doses along with the donor-specific intravenous presensitization, and an immune mechanism other than well-characterized veto T cells is working in this model in suppressing alloreactive CTL precursors.

[Evaluation of the management of blunt renal trauma and indication for surgery].

OBJECTIVES: Appropriate management of renal trauma is still controversial. Many of the patients have minor injuries and conservative treatment can achieve excellent outcomes without any complications. For major injuries of deep lacerations or ruptures, we have been performing early surgical treatment to salvage the kidney in the selected cases after the precise evaluation of the injury. To obtain the optimal management options, we evaluated the clinical results of our procedures. PATIENTS AND METHODS: We conducted a retrospective study, which included 106 cases of blunt renal trauma with evident etiology over the past 22 years and 9 months. The severity of the injury was evaluated mainly by CT scanning. The indication of renal exploration included persistent renal bleeding, large hematoma around the kidney, dislocated fragments, nonviable tissue, massive urinary extravasation and vascular injury. With the patients who required an operation, we first controlled the bleeding by clamping the hilar vessels. Then, the final decision whether to repair or remove the kidney was made based on the direct inspection of the injured kidney after the complete removal of the hematoma. The severity of renal trauma was classified by the classifications found in The Organ Injury Committee of the American Association for the Surgery of Trauma. RESULTS: Sixty-three patients were managed conservatively without any interventions, while 22 surgical repairs and 21 nephrectomies were performed. Of the 63 patients, 35 patients (81.4%) were operated on within 2 days after the injury. Judging from systolic blood pressure, red cell count, blood loss during surgery and transfusion requirements, surgically treated patients were more severely injured than conservatively treated patients. And nephrectomized patients than surgically repaired patients. All the surgically repaired cases were confirmed to have preserved renal functions postoperatively. In all of the 50 patients with Grade I injuries, conservative treatment was successful. Eight out of the 19 Grade II and III cases, who were indicated for kidney exploration because of multiple lacerations or considerable bleeding, were also successfully repaired. Localized hematoma with no urine leakage, even when it was large, settled spontaneously without complication. For the 37 Grade IV and V injuries, including 4 cases with hilar injuries, we implemented conservative procedures on 2 patients, surgical repair on 14 patients and nephrectomy on 21 patients. In the conservatively treated cases, one deep laceration with relatively large, but localized, hematoma, and minimal urine extravasation healed spontaneously. Atrophy of the segment and hypertension developed in the other ruptured kidney with dislocated fragments, large hematoma and urine leakage. This kidney, which also required later surgical exploration, did have good parenchymal blood flow. Hilar injury cases were all resulted in nephrectomy. CONCLUSION: In most of our cases the indication for surgical exploration or nephrectomy based on our criteria seemed to be properly decided. Several cases, though, might have received overtreatment. Recent advances in evaluations and strategies of renal trauma have decreased the need for surgical exploration. This may have overreached the indication for conservative management. Severely injured kidneys may be managed conservatively because in most cases bleeding settles after the full formation of large hematoma within the Gerota's fascia. In such cases, though, no one can predict whether the injury will heal spontaneously or not, and, moreover, whether a complication will develop or not. We think that the optimal management of the patient requires an accurate evaluation of the injured kidney. Therefore the indication for surgical exploration should be made based on the degree of the injury.