Ibuki Tsuru

Supplementary Table 1. Data summary of patients on dialysis. Supplementary Table 2. Significantly mutated genes in tumor in patients on dialysis. Supplementary Table 3. Data summary of patients not on HD. Supplementary Table 4. Genes sepcific to ACD. Supplementary Table 5. Gene list of pure PT cells. Supplementary Table 6. Genes sepcific to the cyst cluster. Supplementary Table 7. Recurrently mutated genes detected in LMD.

Supplementary Figure 1: a, Frequencies of mutations identified in ACD-RCC (left), ESRD-ccRCC (middle), and sporadicccRCC (right). Supplementary Figure 2: a, UMAP plot of the transcriptomes of tumours from HD patients. Supplementary Figure 3: a, eGFR in the expression-defined cluster groups. The green and pink groups correspond to the groups shown in Figure 3a. Supplementary Figure 4: a, Representative images of each marker via mIHC. Supplementary Figure 5: a, Spatial expression patterns of PT genes and DT genes in the renal cortex of patients not on HD. Scale bar, 2 mm.

Patients with end-stage renal disease (ESRD) are at increased risk of acquired cystic kidney disease (ACKD) and renal tumors, but the molecular basis of such disorders remains elusive. In this study, we performed spatial immunogenomic analyses on 268 specimens from 43 patients with ACKD and associated tumors. The molecular landscape of ESRD-associated tumors is different from that of sporadic renal cell carcinoma. Single-cell and spatial analyses have shown that ACKD is under an inflammatory environment and that the renal cysts in ACKD are derived from proximal tubular cells that have survived the destructive effects of inflammation. Interestingly, we revealed that cysts are formed by clonal expansion and that paracrine activation of the MET tyrosine kinase pathway by the surrounding environment nurtures cysts. Collectively, our results identify the oncogenic mechanisms of ESRD-associated renal tumors and will pave the way for improving the prognosis of patients with ESRD.Significance:We elucidated the molecular basis of renal cancer arising in patients with ESRD and show that the inflammatory environment of ESRD gives rise to field cancerization.See related commentary by Sager et al., p. 426

Supplementary Figure 6: a, Expression patterns of PT-related gene sets in UMAP plots of the integrated scRNA-seq data of the renal cortex of 5 HD patients with ACD-RCC. Supplementary Figure 7: a, Inferred CNV profiles of cyst cells with macrophages used as references. The yellow and green clusters in each figure represent heterogeneous expression clusters of cells within the same cyst. Supplementary Figure 8: a, Expression levels of HGF (macrophage) and MET (cyst) genes in UMAP plots of the integrated scRNA-seq data.

Patients with end-stage renal disease (ESRD) are at increased risk of acquired cystic kidney disease (ACKD) and renal tumors, but the molecular basis of such disorders remains elusive. In this study, we performed spatial immunogenomic analyses on 268 specimens from 43 patients with ACKD and associated tumors. The molecular landscape of ESRD-associated tumors is different from that of sporadic renal cell carcinoma. Single-cell and spatial analyses have shown that ACKD is under an inflammatory environment and that the renal cysts in ACKD are derived from proximal tubular cells that have survived the destructive effects of inflammation. Interestingly, we revealed that cysts are formed by clonal expansion and that paracrine activation of the MET tyrosine kinase pathway by the surrounding environment nurtures cysts. Collectively, our results identify the oncogenic mechanisms of ESRD-associated renal tumors and will pave the way for improving the prognosis of patients with ESRD. Significance: We elucidated the molecular basis of renal cancer arising in patients with ESRD and show that the inflammatory environment of ESRD gives rise to field cancerization. See related commentary by Sager et al., p. 426

Introduction: Pelvic arteriovenous malformations are rare in male patients. We present a case of pelvic arteriovenous malformation involving the seminal vesicle.Case presentation: A 58‐year‐old man was diagnosed with pelvic arteriovenous malformation that involved the left seminal vesicle by angiography. The patient underwent three embolization procedures and made favorable progress after the embolizations.Conclusion: Herein, we report a rare case of pelvic arteriovenous malformation involving the seminal vesicle treated by embolizations with good outcome.

IntroductionPatients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome have high risks of uterine and cutaneous leiomyomas and renal cell carcinoma (RCC), which are caused by germline mutation of the fumarate hydratase (FH) gene. RCC lesions are mostly high-grade tumors with a poor prognosis.Case presentationA 37-year-old man who had previously undergone treatment for a left RCC was referred to our hospital with a diagnosis of right RCC. Robot-assisted partial nephrectomy was performed, and the pathological diagnosis revealed fumarate hydratase (FH)-deficient RCC. The left RCC, which was originally diagnosed as mucinous tubular and spindle cell carcinoma, was reviewed and diagnosed as FH-deficient RCC. The patient's father and uncle both died of RCC, and the father's tumor was also immunohistochemically proven to be FH-deficient RCC.ConclusionHLRCC-related RCC should be considered in a differential diagnosis of young patients with a family history of RCC.

IntroductionCondyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma.Case presentationA 42-year-old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad-base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high-grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin-embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas.ConclusionWe report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.

Introduction: Subcutaneous emphysema is a relatively common complication in laparoscopic surgery. However, airway obstruction secondary to subcutaneous emphysema is rare.Case presentation: A 63‐year‐old woman with a 56‐mm left renal tumor underwent a robot‐assisted partial nephrectomy. The operative time was 155 min, the insufflation time was 108 min, and the estimated blood loss was 70 mL. The pneumoperitoneum pressure was maintained at 12 mmHg, except at 15 mmHg for 19 min during tumor resection. The end‐tidal CO₂ was <47 mmHg throughout the procedure. Postoperatively, broad subcutaneous emphysema from the thigh to the eyelid was observed. Computed tomography revealed airway obstruction, and extubation was aborted. On postoperative day 1, emphysema around the trachea and neck improved and the intubation tube was successfully removed.Conclusion: Both laryngeal emphysema and physical compression secondary to emphysema can cause airway obstruction. To reduce gas‐related complications, the risk of developing subcutaneous emphysema should be properly assessed during robot‐assisted laparoscopic surgery.

Introduction: Intravesical Bacillus Calmette–Guérin immunotherapy is an effective treatment for non‐muscle‐invasive bladder cancer, which is occasionally associated with side effects and complications. The incidence of significant renal complications after intravesical Bacillus Calmette–Guérin immunotherapy is less than 2%. We report a case of renal granuloma after intravesical Bacillus Calmette–Guérin immunotherapy for bladder cancer, which radiologically resembled a papillary renal cell carcinoma.Case presentation: A 65‐year‐old man, who had a medical history of urothelial carcinoma and received intravesical Bacillus Calmette–Guérin therapy, was referred to our Urology Department with a right renal tumor. Imaging findings suggested papillary renal cell carcinoma. Robot‐assisted partial nephrectomy was performed, and the histopathological examination revealed epithelioid cell granuloma, which were considered to be Bacillus Calmette–Guérin‐related renal granuloma.Conclusion: Bacillus Calmette–Guérin‐related renal granuloma mimicking papillary renal cell carcinoma have been reported. We should consider the possibility of renal granulomas when encountering image abnormalities for patients treated with intravesical Bacillus Calmette–Guérin therapy.