Vision-based estimation of manipulation forces by deep learning of laparoscopic surgical images obtained in a porcine excised kidney experiment.

In robot-assisted surgery, in which haptics should be absent, surgeons experience haptics-like sensations as "pseudo-haptic feedback". As surgeons who routinely perform robot-assisted laparoscopic surgery, we wondered if we could make these "pseudo-haptics" explicit to surgeons. Therefore, we created a simulation model that estimates manipulation forces using only visual images in surgery. This study aimed to achieve vision-based estimations of the magnitude of forces during forceps manipulation of organs. We also attempted to detect over-force, exceeding the threshold of safe manipulation. We created a sensor forceps that can detect precise pressure at the tips with three vectors. Using an endoscopic system that is used in actual surgery, images of the manipulation of excised pig kidneys were recorded with synchronized force data. A force estimation model was then created using deep learning. Effective detection of over-force was achieved if the region of the visual images was restricted by the region of interest around the tips of the forceps. In this paper, we emphasize the importance of limiting the region of interest in vision-based force estimation tasks.

Renal cell carcinoma with multiple bone metastases effectively treated by a combination of tyrosine kinase inhibitor, robot-assisted partial nephrectomy, and metastasectomy.

Key Clinical Message: Maintaining a disease-free status for a long time in cases of renal cell carcinoma with multiple bone metastases and repeated recurrences is challenging. What matters most in the multidisciplinary approach is the treatment strategy. Although this is a case where multidisciplinary treatment resulted in long-term CR during the TKI era, the treatment strategy is still relevant now that treatment options have increased. Abstract: Recent advances in medications, such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have improved metastatic renal cell carcinoma (mRCC) outcomes. We report a case of mRCC with bone metastasis that was successfully treated using a multidisciplinary approach. Here, we present a case of a 56-year-old man with left renal cancer and large and painful bone metastases at the 11th thoracic vertebrae (Th11). Therefore, a metastasectomy of Th11 was performed. Systemic treatment with TKI, robot-assisted partial nephrectomy, and metastasectomy were then administered. No recurrence was observed in >2 years. Long-term disease-free survival with the TKI-era multidisciplinary approach in a patient with mRCC remains significant when considering treatment sequences, especially now that drug treatment options-including ICIs-have increased. Treatment strategy and indication and timing of resection of the primary lesion and metastasectomy should be carefully considered in each case.

Extracellular vesicles secreted from bone metastatic renal cell carcinoma promote angiogenesis and endothelial gap formation in bone marrow in a time-dependent manner in a preclinical mouse model.

Introduction: Bone is a major metastatic site of renal cell carcinoma (RCC). Recently, it is well recognized that bone metastatic tumor cells remodel bone marrow vasculature. However, the precise mechanism underlying cell-cell communication between bone metastatic RCC and the cells in bone marrow remains unknown. Extracellular vesicles (EVs) reportedly play crucial roles in intercellular communication between metastatic tumor cells and bone marrow. Therefore, we conducted the current study to clarify the histological alteration in vascular endothelium in bone marrow induced by EVs secreted from bone metastatic RCC cells as well as association between angiogenesis in bone marrow and bone metastasis formation. Materials and methods: We established a bone metastatic RCC cell line (786-O BM) by in vivo selection and observed phenotypic changes in tissues when EVs were intravenously injected into immunodeficient mice. Proteomic analysis was performed to identify the protein cargo of EVs that could contribute to histological changes in bone. Tissue exudative EVs (Te-EVs) from cancer tissues of patients with bone metastatic RCC (BM-EV) and those with locally advanced disease (LA-EV) were compared for in vitro function and protein cargo. Results: Treatment of mice with EVs from 786-O BM promoted angiogenesis in the bone marrow in a time-dependent manner and increased the gaps of capillary endothelium. 786-O BM EVs also promoted tube formation in vitro. Proteomic analysis of EVs identified aminopeptidase N (APN) as a candidate protein that enhances angiogenesis. APN knockdown in 786-O BM resulted in reduced angiogenesis in vitro and in vivo. When parental 786-O cells were intracardially injected 12 weeks after treatment with786-O BM EVs, more bone metastasis developed compared to those treated with EVs from parental 786-O cells. In patient samples, BM-EVs contained higher APN compared to LA-EV. In addition, BM-EVs promoted tube formation in vitro compared to LA-EVs. Conclusion: EVs from bone metastatic RCC promote angiogenesis and gap formation in capillary endothelium in bone marrow in a time-dependent manner.

Efficacy and Tolerability of Second-line Pembrolizumab With Radiation Therapy in Advanced Urothelial Carcinoma.

BACKGROUND/AIM: Considering the limited data available on immune checkpoint inhibitors and radiation combination therapy in advanced urothelial carcinoma, this study evaluated the survival benefit and associated toxicity of adding radiation therapy to second-line pembrolizumab. PATIENTS AND METHODS: We retrospectively examined 24 consecutive patients with advanced bladder or upper urinary tract urothelial carcinoma and for whom second-line pembrolizumab was initiated between August 2018 and October 2021 in combination with radiation therapy (with curative intent in 12 patients, and palliative intent in 12 patients). Their survival outcomes and toxicities were compared with those of propensity-score-matched cohorts from a Japanese multicenter study with similar characteristics who received pembrolizumab monotherapy. RESULTS: The median follow-up periods after pembrolizumab initiation were 15 months for the curative cohort and 4 months for the palliative cohort. The median overall survival was 27.7 months for the curative cohort and 4.8 months for the palliative cohort. Compared with the matched pembrolizumab monotherapy cohort, overall survival was better among the curative cohort although not statistically significant (p=0.13), but similar between the palliative and matched pembrolizumab monotherapy cohorts (p=0.44). There was no difference in the incidence of grade ≥2 adverse events between the combination and monotherapy cohorts, irrespective of the intent of radiation therapy. CONCLUSION: The combination of radiation therapy and pembrolizumab can be performed with a clinically acceptable safety profile, and the addition of radiation therapy to immune checkpoint inhibitors may improve survival outcome after pembrolizumab treatment in cases where the intent of radiation therapy is curative.

Analysis of trifecta outcomes in a single center with robot-assisted partial nephrectomy for T1b renal tumors.

INTRODUCTION: This study was performed to investigate the preoperative factors associated with difficulty achieving trifecta in robot-assisted partial nephrectomy for clinical T1b renal cell carcinoma. METHODS: Among 187 patients who underwent robot-assisted partial nephrectomy at our hospital from March 2012 to February 2022, we retrospectively examined 30 patients with unilateral single clinical T1b renal cell carcinoma with at least 6 months of postoperative follow-up, excluding patients with hereditary disease. The following factors were examined in detail: patient-related factors, perioperative factors, surgical techniques, tumor factors, and R.E.N.A.L. nephrometry scores. We examined the preoperative factors associated with difficulty achieving trifecta. A positive surgical margin was pathologically defined as the presence of tumor cells at the margin of the resected specimen or visually defined as intraoperative tumor incision or pseudocapsular damage. RESULTS: Of the 30 patients in this study, 12 achieved trifecta and 18 did not. The reasons for not achieving trifecta were a warm ischemia time of >25 min (66.7%), positive surgical margin (23.3%), and Clavien-Dindo grade ≥3 complications (13.3%) (with overlapping factors). No patients had a pathologically positive surgical margin. Visually positive surgical margins were confirmed by the surgical records and surgical videos. Achieving trifecta was challenging in the multivariate analysis when the "L" component of the R.E.N.A.L. nephrometry score was ≥2 points. CONCLUSION: A preoperative "L" component of ≥2 points in the R.E.N.A.L. nephrometry score was associated with difficulty achieving trifecta.

Retroperitoneal malignant extra-gastrointestinal neuroectodermal tumor with EWSR1::CREM fusion and IL-6-related systemic inflammatory symptoms: a case report.

Malignant gastrointestinal neuroectodermal tumors (GNETs) are mesenchymal tumors that typically arise in the digestive tract and harbor EWSR1::ATF1 or EWSR1::CREB1 fusions. We report a case of primary retroperitoneal GNET in a 38-year-old woman who presented with a month-long fever with increased serum IL-6 level. A right retroperitoneal mass of 7 cm consisting of diffuse sheets of small cells with a high nuclear-to-cytoplasmic ratio and scattered osteoclast-like multinucleated giant cells was confirmed apart from the digestive tract. Peripheral lymphoid cuff and focal pseudoangiomatous spaces were present, reminiscent of angiomatoid fibrous histiocytoma. The tumor cells were positive for S100 protein and SOX10 and negative for melanocytic markers. Fluorescent in situ hybridization revealed EWSR1 and CREM gene rearrangements, consistent with EWSR1::CREM fusion, which has never been reported in GNET. The patient lives with recurrent lesions for 8 months. This case was associated with several unusual features and contributes to the evolving GNET concept.

The efficacy of sequential therapy with docetaxel and cabazitaxel for castration-resistant prostate cancer: A retrospective multi-institutional study in Japan.

OBJECTIVE: This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data. METHODS: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment. RESULTS: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030). CONCLUSIONS: For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.

Paraurachal paraganglioma.

Introduction: Paragangliomas (PGLs) are frequently reported around the abdominal aorta; however, are extremely rare near the urachus. Case presentation: A 78-year-old woman was referred to the urology department of our hospital for further examination and treatment of a 1.2-cm tumor in the lower abdominal wall, a tumor excision was then performed. On immunohistochemical staining, the tumor and supporting cells were positive for chromogranin A and the S 100 protein, respectively, and were diagnosed as PGL. The PGL was thought to be derived from chromaffin cells that migrated to the wall of the urachus during embryonic life and remained even after the wall regressed. Conclusion: We report a case of PGL near the urachus that can be explained by the distribution of the sympathetic network around the midline of the lower abdominal wall during embryonic development. Therefore, PGL should be considered in the differential diagnosis of periurachal tumors.

Limited predictive impact of tumor size dynamics on further tumor shrinkage after 4 cycles of first-line chemotherapy in patients with advanced urothelial carcinoma.

PURPOSE: To investigate the correlation between tumor size changes during the initial 4 cycles of first-line chemotherapy and tumor shrinkage following 2 additional cycles of chemotherapy in patients with advanced urothelial carcinoma (aUC) who experienced disease control after initial chemotherapy. METHODS: We retrospectively reviewed 128 patients with aUC who received first-line chemotherapy. We analyzed 51 patients with disease control (stable disease or better) at the end of the fourth cycle. Of these, 47 patients received 1 to 2 additional cycles of chemotherapy, whereas the remaining patients underwent observation. For patients who received additional chemotherapy, the change in tumor size after additional chemotherapy (cycles 5-6) was defined as "no shrinkage" (tumor growth), "minor shrinkage" (no tumor growth or ≤10% reduction in tumor size), or "shrinkage" (>10% reduction in tumor size). Then, we investigated the relationship between the rate of tumor size change during the initial 4 cycles and that after additional chemotherapy. RESULTS: Of the patients who received additional chemotherapy, the change in tumor size was categorized as no shrinkage in 21 patients (44.7%), minor shrinkage in 18 patients (38.3%), and shrinkage in 8 patients (17%). Regarding predictors of tumor shrinkage after additional chemotherapy, the rate of tumor size change between the cycles 3 and 4 (area under the receiver operating characteristics curve = 0.642) was correlated with the trend of the tumor shrinkage (P = 0.009) and the likelihood of beneficial tumor shrinkage after additional chemotherapy (minor shrinkage + shrinkage; P = 0.02). However, the change in tumor size between cycles 1 and 2, cycles 1 and 4, or cycles 3 and 4 was not satisfactorily predictive of further tumor shrinkage because of substantial overlaps of the tumor size changes. CONCLUSIONS: Only a small subset of patients would have substantial tumor shrinkage by additional cycles after successful induction of 4 cycle chemotherapy. Tumor size dynamics during the initial 4 cycles of chemotherapy displayed limited ability to predict the subset of patients with further tumor shrinkage after additional chemotherapy. Therefore, it might be better to consider switch maintenance immunotherapy for patients who experience disease control after the fourth cycle of first-line chemotherapy.

Incomplete sagittal septum of the bladder with cystolithiasis.

Introduction: Incomplete sagittal septum of the urinary bladder is an extremely rare congenital anomaly and one of the variations in bladder duplication. Herein, we report a case of incomplete sagittal septum of the bladder with cystolithiasis. Case presentation: A 20-year-old man was referred to our department for examination and treatment of symptomatic cystolithiasis and a suspected giant ureterocele on the left side. Cystoscopy and urography performed under general anesthesia revealed anatomical structures suggestive of the sagittal septum of the bladder. Subsequently, transurethral septostomy and cystolithotripsy were performed. The detrusor muscle was microscopically identified, leading to the diagnosis of an incomplete sagittal septum of the bladder. Conclusion: Although extremely rare, an incomplete sagittal septum of the bladder may be difficult to differentiate from a ureterocele, and should be considered when a large cystic lesion is found in the bladder.

[A Retrospective Study of Lymph Node Dissection for Renal Cell Carcinoma].

We retrospectively analyzed the effect of lymph node dissection (LND) in patients with renal cell carcinoma (RCC). Of 151 patients who underwent nephrectomy for RCC, 86 underwent LND. No distant metastasis (M0) was present in 71 patients, although distant metastasis (M1) was present in 15. Three (4.2%) and eight (53%) patients in the M0 and M1 groups, respectively, were clinical N-stage positive. Two (2.8%) and three (20%) patients in the M0 and M1 groups, respectively, were pathological N-stage positive. Both pathological N stage-positive patients in the M0 group were pathologically diagnosed with microphthalmia transcription family translocation RCC. The clinical and pathological positive node areas exhibited concordance in all three pathological N stage-positive patients in the M1 group. Chylous leakage occurred in 16 (19%) patients in the LND group (p＜0.05). Extended LND was a statistically significant risk factor for chylous leakage in the multivariate analysis. Only limited cases should undergo LND, owing to the low frequency of positive pathological lymph node metastasis, and high complication rate.

[Tumor Lysis Syndrome in a Patient with Germ Cell Tumor : A Case Report].

A 36-year-old man presented to our hospital with right scrotal swelling. A computed tomographic scan revealed a mass in the right scrotum, multiple masses in the lung and liver, and enlarged cervical, mediastinal, and retroperitoneal lymph nodes. After right high orchiectomy, he was diagnosed with nonseminomatous germ cell tumor (pT3N3M1b), with poor risk prediction according to the International Germ Cell Consensus classification. We started chemotherapy with bleomycin, etoposide, and cisplatin. Since serum alphafetoprotein (AFP) and human chorionic gonadotropin (HCG) levels did not decrease to normal levels, second-line chemotherapy with paclitaxel, ifosfamide, and cisplatin was administered. Six days after the start of treatment, the patient became unconscious, and his blood pressure decreased. Seven days later, blood tests revealed high uric acid levels, hyperphosphatemia, and increased creatinine. This was diagnosed as tumor lysis syndrome. Following diagnosis, continuous hemodiafiltration was started, and his condition gradually improved.

A novel missense mutation in the folliculin gene associated with the renal tumor-only phenotype of Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome is an autosomal dominant disease caused by germline mutations in the folliculin gene (FLCN), characterized by skin fibrofolliculomas, pulmonary cysts, and multiple renal tumors. We report the case of a 51-year-old woman with multiple bilateral renal tumors resected by bilateral open partial nephrectomy. Following pathological diagnosis of hybrid oncocytic/chromophobe tumors, targeted next-generation sequencing of FLCN of the patient's blood revealed a novel missense mutation (c.602A>C, p.Gln201Pro) in exon 6. Sanger sequencing revealed that this mutation was heterozygous. In silico prediction programs consistently indicated the mutation as pathogenic. Western blot analysis and immunohistochemistry revealed suppressed FLCN expression and the upregulation of glycoprotein nonmetastatic B, a downstream target negatively regulated by FLCN, in the tumor tissue, suggesting that the mutation resulted in reduction of functional FLCN expression. Whole-genome sequencing of one of the tumors identified another frameshift mutation in exon 4, suggesting a "second hit" leading to tumorigenesis. We recommend that gene sequencing should be considered in patients with multiple renal tumors to identify their genetic predisposition to renal tumors.

[Diagnostic Accuracy of Transperineal MRI-Ultrasound Fusion Biopsy at the Introduction Period].

Magnetic resonance imaging (MRI) ultrasound fusion biopsy is becoming popular owing to the better detection rate of clinically significant prostate cancer (csPCa). We retrospectively evaluated the accuracy of MRI-targeted biopsy during the period of introduction at a single academic center by comparing findings of its specimen and whole-mount histopathology. Between June 2018 and January 2021, 106 transperineal MRI-ultrasound fusion biopsies using BioJet software were performed. Among the cases, 15 subsequently underwent robotic-assisted laparoscopic radical prostatectomy and were eligible for analysis. This study included all regions of interest (ROIs) with a Prostate Imaging Reporting and Data System v2 category of 3 or greater on pre-biopsy MRI．For each lesion, grade group of MRI-targeted biopsy specimens and prostatectomy specimens were compared. From a total of 25 ROIs identified among 15 males, csPCa was found in 21 (84%) of the concordant locations of prostatectomy specimens. However, MRI-targeted biopsy could diagnose csPCa in only 12 (48%) of them. In the csPCa undetected group, the ROI volume was significantly smaller (median volume 0.23 ml vs 0.40 ml, p＝0.03). We also found that in cases where PCa was not detected through MRI-targeted biopsy, the biopsy sample length was significantly shorter (median length 9 mm vs 17 mm, p＝0.01). Our data suggest that failure of detecting PCa in MRI-targeted biopsy could be due to technical errors at the introduction period of the technique. A sufficient sampling length of 10 mm or more is desirable, especially for small lesions.

Rapidly Progressive Bladder Cancer Diagnosed because of Spontaneous Bladder Rupture.

Background: Spontaneous bladder rupture (SBR) is very rare and can be associated with advanced bladder cancer. Because of its rarity, the optimal management of bladder cancer with SBR has not been established. Herein, we report a case of SBR due to locally advanced bladder cancer, which rapidly invaded the ileum and caused peritoneal dissemination. Case Presentation. An 86-year-old man presented with sudden-onset lower abdominal pain and distension. The patient was diagnosed with bladder perforation and bladder tumor on contrast-enhanced computed tomography (CECT). Transurethral resection of the bladder tumor revealed an invasive urothelial carcinoma with squamous differentiation. Although radical cystectomy with lymph node dissection was planned, preoperative CECT and magnetic resonance imaging revealed enlargement of the bilateral iliac regional lymph nodes, multiple peritoneal nodules, and invasion of the bladder tumor to the ileocecum. Therefore, cystectomy and resection of ileocecum with palliative intent and bilateral cutaneous ureterostomy were performed. However, the patient's general condition rapidly worsened after surgery, and he died 74 days after the initial diagnosis. Conclusions: We encountered a case of SBR accompanied by bladder cancer with extremely rapid progression, which suggested the importance of short-interval repeat imaging examinations. Emergency surgery should be considered when bladder cancer is suspected in patients with SBR so as not to miss the window period of a possible cure.

Robot-assisted partial nephrectomy for renal cell carcinoma in the isthmus of horseshoe kidney.

The anatomic features of a horseshoe kidney are unique-the kidney is fixed and poorly mobile, with many arterial and venous blood supplies, thereby complicating minimally invasive surgery for renal cancer in this setting. Several reports have described robot-assisted partial nephrectomy (RAPN) to treat renal cancer in a horseshoe kidney, but no reports of RAPN for renal cancer in the isthmus of a horseshoe kidney have been published to date. This case report describes the technique and usefulness of RAPN for treatment of renal cancer located in the isthmus of a horseshoe kidney.

A case of microsatellite instability-high clinically advanced castration-resistant prostate cancer showing a remarkable response to pembrolizumab sustained over at least 18 months.

Defective DNA mismatch repair genes can lead to microsatellite instability (MSI)-high status in prostate cancer (PC). Accumulation of replication errors in DNA leads to the production of abundant neoantigens, which could be targets for immune checkpoint inhibitors (CPIs). However, the incidence of MSI-high PC is low, and not all patients show a satisfactory therapeutic response to CPIs. Here, we present the case of a patient with MSI-high castration-resistant PC who showed a remarkable and durable response to pembrolizumab. The patient was resistant to abiraterone, docetaxel, and cabazitaxel and was suffering from multiple tumor-associated or treatment-related complications, such as urinary tract infection, infective endocarditis, and uncontrollable prostatic hemorrhage. Soon after the start of pembrolizumab therapy, the patient showed a dramatic decrease in prostate-specific antigen from 35.67 ng/mL to an undetectable level and a remarkable reduction in the size of a massive prostate mass and lymph node metastases, with an absence of treatment-related complications. Specimens from the transurethral resection of prostate cancer during cabazitaxel treatment for control of prostate bleeding and also that from the prostate biopsy at initial diagnosis revealed MSI-high status. Immunohistochemistry showed loss of MSH2 and MSH6, and whole-exome sequencing revealed an approximate tumor mutation burden of 61 mutations/Mb as well as biallelic loss of MSH2 Pembrolizumab could show a significant effect even in a heavily treated patient with MSI-high advanced PC. Accumulation of detailed clinical and genomic information of cases of MSI-high PC treated with pembrolizumab is necessary for optimal patient selection.

A rare case of intestinal lymphangiectasia induced by pazopanib.

A 62-year-old man underwent left radical nephrectomy for left renal cell carcinoma at our hospital in 1999. At the age of 79 years, he was diagnosed with intra-abdominal disseminations, lung metastases, pancreas metastases, and bilateral femoral muscle metastases during a routine follow-up computed tomography scan. The patient began treatment with pazopanib. Four years later, at the age of 83 years, he developed fever, abdominal pain, and general malaise. Blood samples showed liver dysfunction, hypoalbuminemia, and anemia. Contrast-enhanced computed tomography showed thickening of the small bowel wall with marked edema of the submucosa from the third part of the duodenum to the jejunum, suggesting intestinal lymphangiectasia. The diagnosis of intestinal lymphangiectasia was confirmed by small bowel endoscopy and histological examination. The patient's general condition improved after discontinuation of pazopanib without the need for any active therapeutic interventions. The possibility of intestinal lymphangiectasia should be considered in patients with hypoalbuminemia and general malaise during treatment with multikinase inhibitors.

IFN-Gamma Expression in the Tumor Microenvironment and CD8-Positive Tumor-Infiltrating Lymphocytes as Prognostic Markers in Urothelial Cancer Patients Receiving Pembrolizumab.

Although immune checkpoint inhibitors have shown benefit for advanced urothelial carcinoma (aUC) patients, prognostication of treatment efficacy and response duration remains a clinical challenge. We evaluated the expression of immune markers in the tumor microenvironment and assessed their associations with response to and survival after pembrolizumab treatment in 26 aUC patients. High levels of CD8+ tumor-infiltrating lymphocytes (TILs) were associated with favorable objective responses (23.0% vs. 15.3%, p = 0.0425), progression-free survival (median, 8.8 vs 2.1 months; hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.07-0.66, p = 0.0060), and overall survival (median, >24.0 vs. 5.3 months; HR, 0.17; 95% CI, 0.04-0.56, p = 0.0034) compared with low levels. High interferon-gamma (IFNγ) expression levels were associated with longer post-progression survival (median, 4.9 vs. 1.0 months; HR, 0.18; 95% CI, 0.04-0.59, p = 0.0027) compared with low expression. Multivariate analysis incorporating clinical prognosticators demonstrated that the coincidence of low CD8+ T cells/IFNγ was an independent factor for unfavorable overall survival after pembrolizumab treatment (HR, 4.07; 95% CI, 1.36-12.73; p = 0.0125). The combination of low CD8+ TILs and IFNγ expression was an independent prognostic factor with predictive ability equivalent to previously reported clinical prognosticators.

Modification of Platinum-based Systemic Chemotherapy for Advanced Urothelial Carcinoma in Patients With Suboptimal Renal Function.

BACKGROUND/AIM: Standard chemotherapy for advanced urothelial carcinoma (UC) patients with moderate renal dysfunction has not yet been established. PATIENTS AND METHODS: We retrospectively assessed outcomes of patients with advanced UC who underwent first-line chemotherapy with full-/reduced-dose gemcitabine plus cisplatin (GC-f/GC-r) or full-/reduced-dose gemcitabine plus carboplatin (G-Car-f/G-Car-r) according to renal function. RESULTS: Seventy-eight patients were included in this study. The objective response rate was 42%, 30%, 42%, and 27% for the GC-f, GC-r, G-Car-f, and G-Car-r groups, respectively. For the GC-r and G-Car-f groups, the median progression-free survival and the median overall survival was 4.5 vs. 7.0 months (p=0.07) and 7.5 months vs. 12.0 months (p=0.124), respectively. Grade 3/4 thrombocytopenia occurred more frequently in the GC-r group than the G-Car-f group (80% vs. 38%, p=0.021). CONCLUSION: G-Car-f could be more beneficial than GC-r for patients with advanced UC who have moderate renal dysfunction.