[Patient-derived renal pelvic carcinoma organoids: establishment and sensitivity to chemotherapeutic drugs].

Renal pelvic carcinoma is a common upper urothelial cancer. The lack of an ideal in vitro model seriously hinders the research progress in the treatment for this disease. This study established a pipeline for the culture of renal pelvic carcinoma organoids based on the tumor tissue samples derived from the patients and tested the organoids to chemotherapeutic drugs. The results of immunohistochemistry and fluorescence experiments confirmed that the renal pelvic carcinoma organoids obtained from culture presented obvious nuclear heteromorphism, which was consistent with the tissue samples from renal pelvic carcinoma patients. The tumor marker molecule CD44 and the cell proliferation marker molecule Ki67 were positive in the organoids, indicating that the organoids were enriched with tumor stem cells and had strong proliferative ability. The renal pelvic carcinoma organoids were highly sensitive to pirarubicin, which had obvious killing effects. In brief, this study successfully established an in vitro model of renal pelvic cancer organoids and tested the sensitivity of the model to chemotherapeutic drugs. The results provide a new laboratory model for the individualized diagnosis and treatment of epithelial carcinomas represented by renal pelvic carcinoma.

A case of seronegative microscopic polyangiitis following the diagnosis of renal pelvic carcinoma.

The incidence rate of malignancy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is higher than that in the general population. Malignancy has been indicated to be a risk factor or inducer of AAV. Herein, we report the case of a healthy 84-year-old man with seronegative microscopic polyangiitis (MPA) after the diagnosis of renal pelvic carcinoma. Four weeks before admission, his estimated glomerular filtration rate (eGFR) was 85 ml/min/1.73 m2, and no hematuria or proteinuria was detected. Renal biopsy on admission revealed invasive urothelial carcinoma of the right renal pelvis. On day 15, his eGFR decreased to 30 ml/min/1.73 m2 without any incitement. The renal specimen extracted via right robot-assisted nephroureterectomy indicated the presence of ANCA-associated glomerulonephritis. On day 37, urinary protein/urinary creatinine level of 6.48 g/gCre, serum albumin level of 2.1 mg/dL, and eGFR of 20 ml/min/1.73 m2 indicated the presence of nephrotic syndrome. His blood sputum was analyzed via chest computed tomography, which revealed alveolar hemorrhage. Although his myeloperoxidase-ANCA was negative, he was diagnosed with MPA based on the 2022 American College of Rheumatology/European League Against Rheumatism classification criteria. This is the first case report of  MPA or AAV complicated with renal pelvic carcinoma. The clinical indicators demonstrated that renal pelvic carcinoma preceded the onset of MPA. The spatial proximity of both diseases indicated that renal pelvic carcinoma had some influence on MPA development via the mechanism of inflammatory cytokines or neutrophil extracellular traps. Our report may be useful in elucidating the mechanism of MPA development.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Primary Synchronous Ipsilateral Renal Fibrosarcoma and Renal Pelvic Carcinoma: A Case Report and Literature Review.

Renal fibrosarcoma is a rare tumor, with only a few cases reported so far, and simultaneous occurrence of ipsilateral renal fibrosarcoma and renal pelvic carcinoma in a patient is extraordinarily rare. A 66-year-old man admitted to our hospital with right renal percutaneous nephrostomy and recurrent fever. And the patient underwent laparoendoscopic nephrectomy and partial ureterectomy for pyonephrotic nonfunctioning kidneys. Postoperative pathology showed fibrosarcoma of right kidney and carcinoma of the renal pelvis. This is the first case of simultaneous occurrence of ipsilateral renal fibrosarcoma and renal pelvic carcinoma in a patient. The diagnosis of fibrosarcoma is one of ultimate immunohistologic exclusion, because there are no specific immunologic markers for fibroblasts. Electron microscopy combined with light microscopy and IHC is helpful for the case of renal fibrosarcoma which is difficult to diagnose. Clinically, radical nephrectomy is the main strategy for primary localized renal fibrosarcoma. At present, it is still necessary to carry out basic biology research to better understand etiology and therapeutical strategy of renal fibrosarcoma.

HER2 Status in Molecular Subtypes of Urothelial Carcinoma of the Renal Pelvis and Ureter.

INTRODUCTION: Erb-b2 receptor tyrosine kinase 2 (ERBB2, also known as HER2) gene amplification or protein overexpression occurs in certain types of urothelial carcinomas. Molecular pathologic classification of urinary bladder cancer using immunohistochemistry has identified basal and luminal subtypes with differing prognoses, but the HER2 status of these subtypes has not been investigated. In addition, research on urothelial carcinoma of the renal pelvis and ureter (UCRPU) has not progressed because of its rarity, though its prognosis is worse than that of bladder cancer. In this study, we evaluated the clinical significance of HER2 status in molecular subtypes of UCRPU. MATERIALS AND METHODS: HER2 status (protein overexpression and/or gene amplification) and molecular subtyping were determined for 148 cases of UCRPU (83 and 65 cases in the renal pelvis and ureter, respectively), using immunohistochemistry and fluorescent in situ hybridization, and compared with clinicopathologic factors. RESULTS: Subtype analysis revealed that the cases were 46% basal and 54% luminal. HER2 protein overexpression and/or gene amplification was observed in 14% of UCRPU cases and was significantly more frequent in the luminal subtype than in the basal (22% vs. 4%; P = .0030). Univariate analysis showed that the overall survival of patients with HER2-positive UCRPU was significantly shorter than those with HER2-negative tumors. CONCLUSIONS: HER2 protein overexpression and gene amplification were specifically observed in the luminal subtype of UCRPU, suggesting that these cases may respond to HER2-targeted therapies like trastuzumab.

[Computed Tomography Imaging Features of IgG4-related Nephropathy].

Objective To investigate the computed tomography(CT)imaging features of IgG4-related kidney disease(IgG4-RKD).Methods The clinicopathological and imaging data of 36 IgG4-RKD patients(including 26 cases of renal parenchyma,10 cases of renal pelvis,24 cases of double kidney or multiple lesions,and 12 cases of single focus)were retrospectively analyzed.Results IgG4-RKD had specific clinicopathological and imaging features.Although the kidney or renal pelvis was involved,there were no common clinical manifestations of malignant tumors such as hydronephrosis and hematuria.The boundary was clear and complete,and it had typical characteristics of continuous progressive enhancement.The peak value was mostly in the solid and excretory phase,and there were no imaging manifestations such as liquefaction,necrosis,cystic degeneration,and calcification.Even if the renal pelvis was obviously involved and the focus was large,there was no invasion of the peripheral renal parenchyma,the shape of the renal pelvis still existed,the wall was smooth,and there was no enlarged peripheral lymph nodes.Conclusions CT images of IgG4-RKD are similar to those of renal malignant tumors.Based on clinicopathological features,CT findings,and blood IgG4-related tests,a definite diagnosis can be made and unnecessary operation can be avoided.

Computed Tomography Imaging Features of IgG4-related Nephropathy / 中国医学科学院学报

Objective To investigate the computed tomography(CT)imaging features of IgG4-related kidney disease(IgG4-RKD).Methods The clinicopathological and imaging data of 36 IgG4-RKD patients(including 26 cases of renal parenchyma,10 cases of renal pelvis,24 cases of double kidney or multiple lesions,and 12 cases of single focus)were retrospectively analyzed.Results IgG4-RKD had specific clinicopathological and imaging features.Although the kidney or renal pelvis was involved,there were no common clinical manifestations of malignant tumors such as hydronephrosis and hematuria.The boundary was clear and complete,and it had typical characteristics of continuous progressive enhancement.The peak value was mostly in the solid and excretory phase,and there were no imaging manifestations such as liquefaction,necrosis,cystic degeneration,and calcification.Even if the renal pelvis was obviously involved and the focus was large,there was no invasion of the peripheral renal parenchyma,the shape of the renal pelvis still existed,the wall was smooth,and there was no enlarged peripheral lymph nodes.Conclusions CT images of IgG4-RKD are similar to those of renal malignant tumors.Based on clinicopathological features,CT findings,and blood IgG4-related tests,a definite diagnosis can be made and unnecessary operation can be avoided.

Urothelial carcinoma with an NRF1-BRAF rearrangement and response to targeted therapy.

Although BRAF mutations are commonly identified in many solid tumors and the response of BRAF p.V600E-positive tumors to targeted therapy is well documented, BRAF rearrangements are less frequent and are predominantly found in low-grade glioma, melanoma, lung, colorectal, and thyroid carcinoma. Preclinical and clinical studies have demonstrated effectiveness of multiple therapies (RAF-targeted, ERK-targeted, or MEK-targeted) targeting BRAF-fusion harboring tumors. We report a rare NRF1-BRAF fusion with novel breakpoints, identified by next-generation sequencing-based assay, from a 69-year-old man with metastatic urothelial carcinoma (UC) of the renal pelvis and his initial clinical response to a second-generation MEK inhibitor, trametinib, before stopping the medication because of adverse side effects. The NRF1-BRAF fusion has only been reported in a single case of anaplastic pleomorphic xanthoastrocytoma, and BRAF rearrangement has never been reported in UC.

IgG4 related disease involving the renal pelvis: a case report and the literature review / 中华泌尿外科杂志

Objective To summarize the characteristics of IgG4 related disease (IgG4-RD),and to avoid unnecessary surgical procedures due to misdiagnosis.Methods Retrospective analysis of the clinical data of one case of IgG4 related disease involving the renal pelvis in our hospital,and the clinical features of IgG4 related disease involving the renal pelvis were reviewed and discussed.A 56-year-old man presented with microscopic hematuria,CT showed right renal pelvis and ureteral wall thickening,local soft tissue density,post contrast CT showed low-density renal pelvic mass and the wall of the ureter-pelvic was irregularly thicken,indicating renal pelvic cancer and lymph node metastasis.PET-CT (18F-FDG) findings indicated that the renal pelvic mass was a malignant tumor,because the glucose metabolism was very high.The preoperative diagnosis was retroperitoneal lesion,suspecting renal pelvic carcinoma or lymphoma.The patient underwent 3D laparoscopic nephroureterectomy with out preoperative biopsy.During operation,we found extensive enlargement of the right renal portal and retroperitoneal lymph nodes,including that the renal portal and the renal pelvis mass had a serious adhesion to the vena cava and renal arterial vein.Results Postoperative pathology results revealed lymphatic tissue hyperplasia and germinal center formation.Immunohistochemical staining showed that most plasma cells positive expression of IgG4 (IgG4 ＞ 40％,IgG4 ＞ 100/HPF),reactive hyperplasia of lymph node,considering the IgG4 related diseases.Serum IgG4 level was 15.2 g/L (0.03-2.01 g/L)after operation.Combined with serological examination,IgG4 related disease was confirmed.There was no evidence of IgG4-related disease at any other site during the follow up period,thereby obviating the need for any additional therapy.Conclusions IgG4 related disease is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells,which leads to the enlargement of the organ or nodular/proliferative lesions.The disease can be revealed as a soft tissue tumor of the renal pelvis and be misdiagnosed as malignant tumor.Surgical intervention could be avoided according to the correct diagnosis.

The value of adding diffusion-weighted images for tumor detection and preoperative staging in renal pelvic carcinoma for the reader's experience.

PURPOSE: This retrospective study aimed to assess the value of adding diffusion-weighted magnetic resonance imaging (DWI) or gadolinium-enhanced fat-suppressed T1WI (CEI) to T2-weighted imaging (T2WI) for preoperative T categorization in renal pelvic carcinoma by the reader's experience using surgical specimens as the reference standard. METHODS: Two radiologists (Reader 1; 3 years, 2; 13 years) reviewed 49 cases with urothelial carcinoma who underwent magnetic resonance imaging examination before surgery, independently, using three image sets: T2WI alone, T2WI plus DWI, and T2WI plus CEI for tumor detection and T categorization. The differences in the apparent diffusion coefficient values between tumors and renal parenchyma, histopathologic grade were analyzed. RESULTS: T2WI plus CEI or DWI had high detection rates (93.4%) compared to T2WI alone. When discriminating T3a/T3b, for Reader 1, the use of T2WI plus DWI (88.0%) and T2WI plus CEI (92.0%) was significantly more accurate than T2WI alone (73%), with AUCs of 0.86, 0.86 and 0.77, respectively. For Reader 2, the accuracies were high on all image sets, with AUCs of 0.87-0.95, and the mean ADC of the tumors was significantly lower than that of the normal renal parenchyma. In addition, the mean ADC values of high-grade tumors were significantly lower than that of low-grade tumors. CONCLUSIONS: DWI and CEI could be more helpful than T2WI alone for preoperative T categorization by less-experienced reader and DWI could be used for preoperative T categorization and for predicting the histopathologic grade of renal pelvic carcinoma.

Image characteristics and early diagnosis of renal pelvic carcinoma:report of 69 cases / 重庆医学

Objective To analyze the typical clinical manifestations and imaging characteristics of renal pelvic carcinoma.Methods The clinical data in 69 cases of renal pelvic carcinoma verified by postoperative pathology in this department of the hospital from July 2013 to November 2016 were retrospectively summarized to analyze its typical clinical manifestations,imaging features and treatment regimens.Results All the cases were hospitalized due to hematuria and presented gross hematuria.The detectable rate of B-ultrasonic examination was 71.43 ％,which of computed tomography urography(CTU) was 84.21％ and which of intravenous urography(IVU) + kidney ureter bladder(KUB) was 70.27 ％,which of retrograde pyelography(RP) was 90.32 ％,which of flexible ureteroscope(FU) was 91.67 ％,the pathological detection rate of biopsy tissue by this method was 58.33 ％ and detection rate of fluorescence in situ hybridization was 79.07 ％.Sixty-nine cases all were performed the retroperitoneal laparoscopy combined with hypogastric incision renal pelvic carcinoma radical operation,postoperative pathological examination verified renal pelvis carcinoma.Conclusion Flexible ureteroscope examination has the highest definite diagnosis rate of renal pelvic carcinoma,but the pathological positive rate of biopsy tissue by this method is not ideal;the definite diagnosis rate of RP and CTU were secondary,urinary system B-ultrasonic examination,FISH and KUB+IVP can serve as the preliminary screening and postoperative re-examination means of renal pelvic carcinoma.

Apparent diffusion coefficient value of 3.0T MR diffusion-weighted imaging in assessing invasiveness of renal pelvic carcinoma / 第二军医大学学报

Objective To investigate the value of 3. 0T MR diffusion-weighted imaging (DWI) in diagnosing the renal pelvic cancer and the association of apparent diffusion coefficient (ADC) value with the histological grade and clinical stage of cancer. Methods The clinical data of 33 patients with renal pelvic carcinoma were retrospectively analyzed. Routine MRI and DWI with b-values of 0 and 800 s/mm2 were performed, and the examination results were compared with the corresponding pathological results. We then calculated the sensitivity, specificity, accuracy, positive and negative predictive values of DWI. The DWI signal characteristics of lesions were recorded and analyzed, and three regions of interest (ROIs), large and small ROIs andminimum ADC (minADC) value, were selected for each lesion. The differences of ADC values between different genders, locations, cancer tissue and normal renal parenchyma, among three ROIs, among different pathological grades, among different clinical stages were compared and analyzed. Immunohistochemical staining was used to detect the expression of Ki-67 in renal pelvic cancer tissues, and the relationship between ADC value and Ki-67 expression was also analyzed. Results The results of DWI with 800 s/mm2 b-value showed that the sensitivity, specificity, accurate rate, positive and negative predictive value for renal pelvic carcinoma were 90. 9%, 91. 4%, 91. 2%, 90. 9% and 91. 4%, respectively. The ADC values were significantly different between normal renal parenchyma and renal pelvic carcinoma tissues (P<0. 05), and they were notsignificantly different between different genders, locations or among small ROI, big ROI and the minADC values. The ADC value of low grade (G1-G2) tumors was significantly higher than that of high grade (G3) ones (P<0. 01). The ADC value of cancer cells confined to the renal pelvis (Ta-T2) was higher than that with local invasion (T3)(P<0. 05). Ki-67 expression was found associated with the pathological grades and tumor stages of pelvic carcinoma, and there was a negative correlation between ADC value and Ki-67 expression (r= —0. 88, P<0. 01). Conclusion Our findings suggest that the size of ROI may be of little value in diagnosis of urothelial carcinoma, and DWI may contribute to the preoperative assessment of histological grade and clinical stages of renal pelvic carcinoma.

Comparative study of six operations for the treatment of upper urinary tract carcinoma / 中国癌症杂志

Background and purpose:Radical nephroureterectomy can be performed in a variety of ways, and each method has its advantages and disadvantages. It still remains controversial for choosing the surgical methods. In this study, we chose six surgical methods and investigated the safety and efficacy of different methods in treating upper urinary tract carcinoma.Methods:We retrospectively analyzed 135 patients with upper urinary tract transitional cell carcinoma who underwent operations in our hospital from Jan. 2002 to Oct. 2013, and compared the data of six different operations in-cluding operating time, volume of bleeding, time of bowel function recovery and incidence of bladder carcinomas.Results:The operations were successfully completed in groups A and B. Five cases in group C were transferred into group A be-cause of failing to pull the nub of the ureter. Two cases in group D were transferred into group A because of failing to pull the nub of the ureter. Three cases in group E were transferred into group D and 1 case was transferred into group A because of adhesion or bleeding. One case in group F was transferred into group A because of bleeding. There was no statistically significant difference in survival rates among six operations.Conclusion:Six operations are all safe and effective for the treatment of upper urinary tract carcinomas. Each method has its advantages and disadvantages. We should choose differ-ent methods according to particular cases.

Renal pelvic carcinoma associated with renal stone / 中华泌尿外科杂志

Objective To discuss the diagnosis and treatment of renal pelvic carcinoma associated with renal stone.Methods A total of 13 patients,aged from 49 to 73 years old and averaged 59years old.The history of renal stone was 16 years.13 patients accepted B ultrasound check and 1 was found soft tissue occupying.8 patients accepted IVU check and none was found soft tissue occupying.7 patients accepted CT scan and 4 were found soft tissue occupying.The fluorescence in situ hybridization (FISH) examination was done for 2 patients and both were positive.6 patients were found lesions at renal pelvis mucous membrane during the operation of percutaneous nephrolithotripsy,4 accepted radical operations of renal pelvic carcinoma and 2 patients accepted radical nephrectomy according to the biopsy pathology.4 were found soft tissue occupying before operation and accepted radical operation of renal pelvic carcinoma ultimately.1 patient suffered gross hematuria and renal insufficiency accepted the renal pelvic carcinoma vaporization under the ureteroscope.Results The pathology showed that 7 cases were transitional cell carcinoma,4 were transitional cell carcinoma combined squamous cell carcinoma (SCC) metaplasia and 2 were squamous cell carcinoma.6 of 8 patients' stone chemical composition were infection stone and 2 were calcic blended stone.3 patients were followed up 1 to 2 years and survival with no tumor recurrence.The tumor recurred 10 months of the patient accepted the operation of renal pelvic carcinoma vaporization and accepted vaporization again.1 patient bsuffered SCC and local lymph node metastasis.He died 13 months post-operation.Conclusions For the patient who had long history of stone,combining infection with symptoms of severe hematuria and postoperation hematuria,the possibility of renal pelvic carcinoma should be considered.CT scan and urine FISH may help for diagnosis.The biopsy should routinely perform for the doubtful mucosa lesion during the cavity stone operation.Early and timely diagnosis and operation is the key for the patients with pelvic carcinoma associated with renal stone.

Contrast-enhanced ultrasonographic diagnosis of renal pelvic carcinoma / 中国医学影像技术

Objective To explore the potential value of contrast-enhanced ultrasonography (CEUS) in diagnosis of renal pelvic carcinoma. Methods The ultrasonogram of conventional ultrasound and CEUS were analyzed retrospectively in 22 patients of renal pelvic carcinoma proved pathologically. The size, echo, boundary and color flow signal of renal pelvic lesions were observed with conventional ultrasound. The enhancement modality and phase of tumors were also observed with CEUS, including wash-in and wash-out time, as well as the perfusion appearances. Results The maximum diameters ranged from 1.5 cm to 8.5 cm in 22 renal pelvic tumors. Conventional ultrasound detected flat mass in 7 tumors, irregular mass in 15 tumors; the same side hydronephrosis in 11 patients. Color Doppler flow imaging (CDFI) disclosed fairly rich flow signal of 5 tumors, a small amount of flow signal around tumor in 9 tumors and no-flow signal in the rest tumors. CEUS detected the cortical phase enhancement in all renal pelvic tumors, including synchronously enhancement in 8 tumors and delayed enhancement in 14 tumors. In peak time, hypoechogenicity compared to the normal renal cortex was showed in 18 tumors, hyperechogenicity in 3 tumors and isoechogenicity in 1 tumor. Fast wash-out in medulla phase was displayed in 20 tumors, isochronously wash-out in 1 tumor and delayed wash-out in 1 tumor. The diagnostic accuracy of the conventional ultrasound and CEUS was 63.64% (14/22) and 81.82% (18/22), respectively. Conclusion CEUS can depict blood flow supply and improve the diagnostic rate of renal pelvic carcinoma.

The Value of Contrast-Enhanced Spiral CT Scan in Diagnosing Renal Pelvic Carcioma / 实用放射学杂志

Objective To invesigate the value of contrast-enhanced spiral CT scan in diagnosing renal pelvic carcinoma.Methods All 35 cases with renal pelvic carcinoma confirmed by surgical pathology underwent plain and contrast-enhanced (including 4 phases) spiral CT scans before operation.CT data were reviewed retrospectively in comparison with surgical and patholgical results.Results CT findings of renal carcinoma could be classified into 3 types:type Ⅰ,the lesions limited within the renal pelvis in 25 cases;thype Ⅱ,the lesions were out of the renal pelvis and had indefinable margins with the renal parenchyma in 6 cases;type Ⅲ ,only showed the pelvic wall thickened with hydronephrosis in 4 cases.On contrast-enhanced CT scan,inhomogeneous enhancement of the lesions was presented in cortical phase,the intensity of enhancement was not obviously changed in 13 cases in parenchymal and excretion phases,but the lesions were still hypointense in comparison with renal parenchyma,14 cases demonstrated inhomogeneous enhancement of the lesions in delayed phase.Conclusion Contrast-enhanced spiral CT scanning is valuable in diagnosing renal pelvic carcinoma and renal delayed phase should be emphasized.