Genomic profiling of Chinese patients with urothelial carcinoma.

BACKGROUNDS: Urothelial carcinoma (UC) is the most common genitourinary malignancy in China. In this study, we surveyed the genomic features in Chinese UC patients and investigated the concordance of genetic alterations between circulating tumor DNA (ctDNA) in plasma and matched tumor tissue. MATERIALS AND METHODS: A total of 112 UC patients were enrolled, of which 31 were upper tract UC (UTUC) and 81 were UC of bladder (UCB). Genomic alterations in 92 selected genes were analyzed by targeted next-generation sequencing. RESULTS: In the study cohort, 94.64, 86.61 and 62.50% of patients were identified as having valid somatic, oncogenic and actionable somatic alterations, respectively. The most frequently altered genes included TP53, KMT2D, KDM6A, FAT4, FAT1, CREBBP and ARID1A. The higher prevalence of HRAS (22.0% vs 3.7%) and KMT2D (59.26% vs 34.57%) was identified in UTUC than in UCB. Comparisons of somatic alterations of UCB and UTUC between the study cohort and western cohorts revealed significant differences in mutant prevalence. Notably, 28.57, 17.86 and 47.32% of the cases harbored alterations in FGFRs, ERBBs and DNA damage repair genes, respectively. Furthermore, 75% of the patients carried non-benign germline variants, but only two (1.79%) were pathogenic. The overall concordance for genomic alterations in ctDNA and matched tumor tissue was 42.97% (0-100%). Notably, 47.25% of alterations detected in ctDNA were not detected in the matched tissue, and 54.14% of which were oncogenic mutations. CONCLUSIONS: We found a unique genomic feature of Chinese UC patients. A reasonably good concordance of genomic features between ctDNA and tissue samples were identified.

A three-dimensional, anatomy-based nephrometry score to guide nephron-sparing surgery for renal sinus tumors.

BACKGROUND: A quantitative nephrometry scoring system specifically for renal sinus tumors will assist in classifying surgical complexity and treatment planning. METHODS: By using preoperative computed tomography, magnetic resonance imaging, and 3-dimensional image reconstruction, 5 critical components were assessed: the ratio of the sinus area occupied by the tumor in relation to the whole sinus area (R), the compression of the renal segmental vessels or collection system by the tumor (O), the anteroposterior relation of the tumor relative to the segmental vessels or collection system (A), the tumor diameter (D), and whether the tumor affects a solitary kidney (S) ("ROADS"). The ROADS score, indicating low, moderate, or high surgical complexity, was then used to guide surgical strategy planning, including cooling techniques, surgical approaches, and parenchyma incision techniques. A cohort of 134 patients with renal sinus tumors was treated based on their ROADS score and was retrospectively analyzed. RESULTS: The authors successfully performed 113 nephron-sparing surgeries and 21 radical nephrectomies with a complication rate of 7.9%. During follow-up, 3 cases were classified according to surgical margin status because they lacked an intact tumor capsule. There was only 1 case of local recurrence, and there were no cases of metastasis. A high ROADS score was correlated with greater operative complexity, such as longer operation and ischemia times and higher estimated blood loss and complication rates. However, renal function and short-term oncologic outcomes were not related to the score. CONCLUSIONS: The ROADS scoring system provides a standardized, quantitative, 3-dimensional anatomic classification to guide surgical strategy in renal sinus tumors.

MRI-based Bosniak Classification of Cystic Renal Masses, Version 2019: Interobserver Agreement, Impact of Readers' Experience, and Diagnostic Performance.

Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test. P < .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively; P < .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively; P = .71) and version 2005 (weighted κ = 0.54 vs 0.46; P < .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% [92 of 111] vs 68% [75 of 111], respectively; P < .001), without any difference in sensitivity (89% [85 of 96] vs 84% [81 of 96]; P = .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Choyke in this issue.

Multiparametric MRI Radiomic Model for Preoperative Predicting WHO/ISUP Nuclear Grade of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Nuclear grade is of importance for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC). PURPOSE: To develop and validate an MRI-based radiomic model for preoperative predicting WHO/ISUP nuclear grade in ccRCC. STUDY TYPE: Retrospective. POPULATION: In all, 379 patients with histologically confirmed ccRCC. Training cohort (n = 252) and validation cohort (n = 127) were randomly assigned. FIELD STRENGTH/SEQUENCE: Pretreatment 3.0T renal MRI. Imaging sequences were fat-suppressed T2 WI, contrast-enhanced T1 WI, and diffusion weighted imaging. ASSESSMENT: Three prediction models were developed using selected radiomic features, radiomic and clinicoradiologic characteristics, and a model containing only clinicoradiologic characteristics. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the predictive performance of these models in predicting high-grade ccRCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) method were used for the selection of radiomic features and clinicoradiologic characteristics, respectively. Multivariable logistic regression analysis was used to develop the radiomic signature of radiomic features and clinicoradiologic model of clinicoradiologic characteristics. RESULTS: The radiomic signature showed good performance in discriminating high-grade (grades 3 and 4) from low-grade (grades 1 and 2) ccRCC, with sensitivity, specificity, and AUC of 77.3%, 80.0%, and 0.842, respectively, in the validation cohort. The radiomic model, combining radiomic signature and clinicoradiologic characteristics, displayed good predictive ability for high-grade with sensitivity, specificity, and accuracy of 63.6%, 93.3%, and 88.2%, respectively, in the validation cohort. The radiomic model showed a significantly better performance than the clinicoradiologic model (P < 0.05). DATA CONCLUSION: Multiparametric MRI-based radiomic model can predict WHO/ISUP grade in patients with ccRCC with satisfying performance, and thus could help the physician to improve treatment decisions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Percutaneous microwave ablation of renal cell carcinoma: practice guidelines of the ultrasound committee of Chinese medical association, interventional oncology committee of Chinese research hospital association.

Imaging-guided percutaneous microwave ablation (MWA) with high thermal efficiency comprises rapid, successful management of small renal cell carcinomas (RCCs) in selected patients. Ultrasound Committee of Chinese Medical Association, Interventional Oncology Committee of Chinese Research Hospital Association developed evidence-based guidelines for MWA of RCCs after systematically reviewing the 1969-2019 literature. Systematic reviews, meta-analyses, randomized controlled trials, cohort, and case-control studies reporting MWA of RCCs were included and levels of evidence assessed. Altogether, 146 articles were identified, of which 35 reported percutaneous MWA for T1a RCCs and 5 articles for T1b RCCs. Guidelines were established based on indications, techniques, safety, and effectiveness of MWA for RCCs, with the goal of standardizing imaging-guided percutaneous MWA treatment of RCCs. Key points Microwave ablation is recommended for managing small renal cell carcinoma in selected patients. Imaging protocols are tailored based on the procedural plan, guidance, and evaluation. Patient's selection evaluation, updated technique information, clinical efficacy, and complications are recommended to standardize management. A joint task force (multidisciplinary team) summarized the key elements of the standardized report.

Minimally Invasive Surgery-Based Multidisciplinary Clinical Management of Reninoma: A Single-Center Study.

BACKGROUND This article presents our experience in managing a rare kidney tumor - reninoma - by analyzing a relatively large series of cases from a single center. MATERIAL AND METHODS Nine cases of reninoma were reviewed. Clinical manifestations, imaging examinations, laboratory examinations, perioperative data, and pathological findings were summarized. A 58.8-month follow-up was performed to evaluate patient survival and recrudescence. RESULTS The main clinical manifestations were hypertension, hypokalemia, headache, dizziness, nausea, vomiting, palpation, and sweating. Three patients had hypertensive end-organ damage, including brain hemorrhage, gestation termination, and grade III ocular fundus changes. All patients underwent retroperitoneal laparoscopic partial nephrectomy successfully. The mean warm ischemic time was 23.4 min. The median operation time was 95.1 min, with a median estimated blood loss of 60 ml. The median hospital stay was 6 days. No serious intraoperative or postoperative complications occurred. The histology and electron microscopy findings confirmed the diagnosis of reninoma in all cases. After 58.8 months of follow-up, symptoms involving hypertension were relieved in all patients, and no tumor recurrence or metastasis was detected. CONCLUSIONS Reninoma may have severe consequences despite being a benign tumor. Retroperitoneal laparoscopic partial nephrectomy is a feasible and effective method for the surgical removal of reninoma. Multidisciplinary cooperation plays an important role in improving the diagnosis and enabling the early surgical treatment of reninoma. Especially in cases of reninoma with moderate and high RENAL scores, an accurate diagnosis of reninoma based on multidisciplinary cooperation facilitates the selection of less invasive surgical approaches.

Diffusion-weighted imaging versus contrast-enhanced MR imaging for the differentiation of renal oncocytomas and chromophobe renal cell carcinomas.

OBJECTIVES: To compare the performance of diffusion-weighted imaging (DWI) with that of contrast-enhanced MRI in differentiating renal oncocytomas from chromophobe renal cell carcinomas (RCCs). METHODS: We recruited 48 patients with histopathologically confirmed renal oncocytomas (n=16) and chromophobe RCCs (n=32). All patients underwent preoperative DWI and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) and signal intensity were measured in each patient. ADC ratio and percentage of signal intensity change were calculated. RESULTS: Mean ADC values for renal oncoctytomas were significantly higher than those for chromophobe RCCs (1.59±0.21 vs. 1.09±0.29× 10-3 mm2/s, p < 0.001). Area under the ROC curve, sensitivity and specificity were 0.931, 87.5% and 84.4%, respectively, for ADC measurement of DW imaging; 0.825, 87.5% and 75%, respectively, for enhancement ratio (p > 0.05). Adding ADC values to the enhancement ratios in the ROC, analysis to differentiate renal oncocytoma from chromophobe RCCs increased specificity from 75 to 87.5% at 87.5% sensitivity without significantly increasing the AUC (0.930). CONCLUSIONS: Both DWI and contrast-enhanced MRI may assist in differentiating renal oncocytomas from chromophobe RCCs, with DWI showing higher diagnostic value. The combination of the two parameters could potentially provide better performance in distinguishing these two tumours. KEY POINTS: • ADC values can assist in differentiating renal oncocytomas from chromophobe RCCs. • DW imaging possesses better specificity than does contrast-enhanced MR imaging. • Combining the two parameters provides higher specificity regarding the differential diagnosis.

Renal epithelioid angiomyolipoma: MRI findings.

PURPOSE: To retrospectively analyze the MR imaging presentation of renal epithelioid angiomyolipoma (EAML). METHODS: Retrospective analysis revealed 12 subjects with histologically proven renal EAML who underwent preoperative MRI at our institution between January 2009 and June 2016. Two radiologists reviewed the images in consensus, describing MR imaging features including size, location, growth pattern, signal intensity of tumor, and dynamic enhancement pattern. RESULTS: Nine women and three men were included. The average maximum tumor diameter was 7.1 cm. Exophytic growth was present in 9/12 cases, mesophytic growth in 2/12, and endophytic growth in 1/12. On T1-weighted images, 2/12 displayed homogeneous isointensity, 1/12 homogeneous hyperintensity, 5/12 heterogeneous hypointensity, and 4/12 heterogeneous hyperintensity. Macroscopic fat was detected in 5/12 cases and microscopic fat in 6/12 cases. On T2-weighted images, 5/12 showed heterogeneous hypointensity, 4/12 heterogeneous hyperintensity, and 3/12 homogeneous hypointensity. On dynamic contrast-enhanced MR images, 7/12 showed a slow washout enhancement pattern, 2/12 a rapid washout pattern, 2/12 progressive enhancement, and 1/12 persistent enhancement. Imaging findings were suggestive of hemorrhage (50%), necrosis (25%), or cystic change (50%) within the tumors. Enlarged vessels were detected in 5/12 cases. One tumor extended into the renal sinus. No metastases were found on the preoperative MR imaging. CONCLUSION: Although MRI appearances of renal EAML were various, some MRI characteristics may contribute to suggest the possibility of renal EAML.

The pathology of urinary bladder lesions with an inverted growth pattern.

Inverted lesions in the urinary bladder have been the source of some difficulty in urological pathology. The two common ones are von Brunn's nests and cystitis cystic/cystitis glandularis, which are considered normal variants of urothelium. Apart from them, a number of other rare urothelial lesions with inverted growth pattern occur in the urinary bladder. Some of them are only reactive conditions, just as pseudocarcinomatous hyperplasia. Some are benign tumors, namely inverted papilloma. Whereas others are malignant neoplasms, including inverted papillary urothelial neoplasm of low malignant potential (PUNLMP), non-invasive inverted papillary urothelial carcinoma (low-grade and high-grade), and invasive urothelial carcinoma (inverted, nested and big nested variants). Because of the overlapping morphological features of all the inverted lesions mentioned above, even between high-grade invasive carcinoma and pseudocarcinomatous hyperplasia which are only a kind of reactive conditions, it is very important for the surgical pathologist to recognize and be familiar with these inverted lesions in urinary bladder. In this article, we review these spectrums of inverted lesions of the urinary bladder. Emphasis is placed on histogenesis, morphology, differential diagnosis of these lesions, and the pathologic grading of the non-invasive inverted neoplasms, such as inverted papilloma, inverted PUNLMP, non-invasive inverted papillary urothelial carcinoma with low-grade, and non-invasive inverted papillary urothelial carcinoma with high-grade.

Role of preoperative sonography in the diagnosis and pathologic staging of pseudomyxoma peritonei.

OBJECTIVES: The purpose of this study was to analyze the sonographic features of pseudomyxoma peritonei and the ability of preoperative sonography to assess the pathologic grades of this disease. METHODS: Nineteen patients with pseudomyxoma peritonei who underwent preoperative sonographic examinations were included (9 male and 10 female; age range, 31-70 years). Four patients presented with disseminated peritoneal adenomucinosis, 7 with peritoneal mucinous carcinomatosis with intermediate or discordant features (intermediate-grade disease), and 8 with peritoneal mucinous carcinomatosis. The sonographic characteristics, clinical features, and serum tumor marker levels were recorded and compared among the 3 grades. RESULTS: Clinical symptoms and carcinoembryonic antigen, cancer antigen 125 (CA-125), CA-19-9, CA-724, and CA-153 levels were not significantly different among the 3 pathologic grades (P > .05). Ascites, scalloping of the visceral margin, invasive parenchymal nodules, and peritoneal masses were detected in all grades. Disseminated peritoneal adenomucinosis occurred without the finding of an omental cake. The presence of enlarged lymph nodes was more common in peritoneal mucinous carcinomatosis. The diagnosis of pseudomyxoma peritonei was made by preoperative sonography in 1 case. Four cases were diagnosed as ovarian mucinous cystadenoma with rupture. One case was diagnosed as a mucinous appendiceal cyst. Four cases were diagnosed as ascites or encapsulated effusion. One case was misdiagnosed as lymphoma. The others were diagnosed as celiac masses. CONCLUSIONS: Preoperative sonography can be used to diagnose pseudomyxoma peritonei as long as radiologists are familiar with the imaging features. Although there are overlaps in the sonographic findings among the different grades, some features may aid in separating them.

[Prognostic value of clinical and pathological characteristics in 48 women with pseudomyxoma peritonei].

OBJECTIVE: To investigate the clinic-pathological characteristics and prognosis of 48 female cases with peritoneal pseudomyxoma(PMP). METHODS: The clinicopathologic features and follow-up data of 48 female patients with PMP diagnosed in the General Hospital of People's Liberation Army from Jan.1982 to Dec.2011 were retrospectively reviewed. The relationship between clinic-pathological characteristics and prognosis were analyzed using log-rank test and Cox proportional hazards model. RESULTS: (1) Clinicopathologic features: the mean age of the 48 cases was 58.8 years (range from 24 to 79 years). SYMPTOMS: abdominal distention and abdominal discomfort were the main symptoms. Imaging examinations showed nonspecific abdominal and pelvic lesions in most cases. TREATMENT: all the 48 patients underwent laparotomy and cytoreductive surgery (CRS), in which 15(31%) patients with completeness of the cancer resection (CCR) -1, 24(50%) cases with CCR-2, and CCR-3 in 9(19%) cases. Six (12%) cases were treated by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin, 20(42%) patients were treated with different options postoperative adjuvant chemotherapy. Pathological types:the cases were histologically classified into 3 subcategories:disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D), which were 22(46%) cases, 9 (19%)cases and 17 (35%)cases, respectively. Appendiceal tumors: 44(92%) cases underwent appendectomy, in which 38 cases presented appendiceal tumors (including 20 cases of low-grade appendiceal mucinous adenoma and 18 cases of appendiceal mucinous adenocarcinoma), 2 cases were diagnosed as appendicitis, 4 cases with unknown pathologic diagnosis. And the other 4(8%) cases, who didn't undergo appendectomy at the first operation, presented peritoneal tumor recurrence and appendiceal mucinous tumors 1, 11, 32 and 85 months after surgery, respectively. Parenchymal organs involved: ovarian involving was happened in 34 (71%) patients including 15 cases with the right ovary involving, 13 cases in both sides, and 6 cases involving the left side. The other parenchymal organs in 10(21%) cases. (2) Prognostic factors: 11 patients died, 31 survived and 6 cases were lost to follow-up. The mean survival time was 99 months(ranged from 1 to 312 months). The 3-year, 5-year and 10-year survival rates were 73.3%, 68.0% and 46.6%, respectively. Univariate statistical analysis showed that age, pathological type and parenchymal involvement were significantly relationship with the survival time (all P < 0.05). But the operation times, appendiceal tumor type, ovarian involvement, CCR, intraperitoneal HIPEC and post-operative adjuvant chemotherapy were not significantly correlate with survival time (all P > 0.05). Multivariate analysis showed that age and pathologic type were independent prognostic factors(P < 0.05). CONCLUSIONS: No specific clinical features presented in PMP. CRS with HIPEC should the recommended treatment. Both ovaries exploration and appendectomy should be carried out routinely in CRS. The 10-year overall survival of PMP is low. Age, pathological type and parenchymal organs involvement other than ovarian are correlated with the prognosis. And the pathological type and age are independent prognostic factors of PMP.

Venous tumor thrombus consistency: is it a prognostic factor of survival for patients with renal cell carcinoma?

OBJECTIVES: To evaluate whether venous tumor thrombus (VTT) consistency is a risk factor for the patient's prognosis with renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 190 RCC patients with VTT, who were treated at Department of Urology, Chinese PLA General Hospital, were retrospectively analyzed in this study. The baseline clinical characteristics, postoperative outcomes, and pathological findings were analyzed. Tumor thrombus was classified as solid and friable based on their respective characteristics. Survival curves were estimated using the Kaplan-Meier survival curve analysis, and univariable and multivariable cox proportional hazard regression models were used. RESULTS: Among the total 190 patients included in this study, 145 (76.3%) patients had solid VTT, and 45 (23.7%) patients had friable VTT in their renal veins and inferior vena cava (IVC). There were no significant differences in the age, gender, BMI, symptoms, complex diseases, tumor side, tumor size, TNM stage, Mayo stage, tumor grade, sarcomatous differentiation, pelvic invasion, and sinus fat invasion of patients. Solid VTT consistency was more likely to have a capsule as compared to those with friable VTT (P = 0.007). Kaplan-Meier survival curve analysis demonstrated no statistically significant differences in the overall survival (OS) (P = 0.973) and progression-free survival (PFS) (P = 0.667) of patients. Moreover, VTT consistency was not associated with OS (P = 0.706) of PFS (P = 0.504) in multivariate cox regression analysis. CONCLUSIONS: RCC VTT consistency was not a prognostic risk factor for predicting the OS and PFS of patients.

Classification of human coronary atherosclerotic plaques using ex vivo high-resolution multicontrast-weighted MRI compared with histopathology.

OBJECTIVE: The objective of our study was to evaluate the feasibility of ex vivo high-resolution multicontrast-weighted MRI to accurately classify human coronary atherosclerotic plaques according to the American Heart Association classification. MATERIALS AND METHODS: Thirteen human cadaver heart specimens were imaged using high-resolution multicontrast-weighted MR technique (T1-weighted, proton density-weighted, and T2-weighted). All MR images were matched with histopathologic sections according to the landmark of the bifurcation of the left main coronary artery. The sensitivity and specificity of MRI for the classification of plaques were determined, and Cohen's kappa analysis was applied to evaluate the agreement between MRI and histopathology in the classification of atherosclerotic plaques. RESULTS: One hundred eleven MR cross-sectional images obtained perpendicular to the long axis of the proximal left anterior descending artery were successfully matched with the histopathologic sections. For the classification of plaques, the sensitivity and specificity of MRI were as follows: type I-II (near normal), 60% and 100%; type III (focal lipid pool), 80% and 100%; type IV-V (lipid, necrosis, fibrosis), 96.2% and 88.2%; type VI (hemorrhage), 100% and 99.0%; type VII (calcification), 93% and 100%; and type VIII (fibrosis without lipid core), 100% and 99.1%, respectively. Isointensity, which indicates lipid composition on histopathology, was detected on MRI in 48.8% of calcified plaques. Agreement between MRI and histopathology for plaque classification was 0.86 (p < 0.001). CONCLUSION: Ex vivo high-resolution multicontrast-weighted MRI can accurately classify advanced atherosclerotic plaques in human coronary arteries.

[Clinical and pathologic characteristics of small cell neuroendocrine carcinoma of urinary tract].

OBJECTIVE: To study the clinical and pathologic characteristics of small cell neuroendocrine carcinoma of urinary tract. METHODS: All cases of urinary tract carcinoma encountered in the General Hospital of People Liberation Army during the period from 1999 to 2010 were retrospectively reviewed. The clinicopathologic data of small cell neuroendocrine carcinomas were further analyzed, with literature review. RESULTS: A total of 16 cases of small cell neuroendocrine carcinoma were identified, including 10 from urinary bladder, 2 from ureter, 3 from renal pelvis, and 1 multifocal tumor involving renal pelvis and ureter. There were altogether 8 males and 8 females. The median age of the patients was 63 years (range = 24 to 79 years). Gross hematuria (11 cases) represented the main presenting symptom. Four patients had flank pain and 4 had urinary irritation symptoms. Seven patients underwent radical cystectomy. Six other patients underwent radical nephroureterectomy, 1 partial cystectomy, 1 TURBT and the remaining case biopsy only. The size of the tumor ranged from 0.8 to 8.0 cm (median = 4.5 cm). Histologically, 15 cases represented mixed small cell neuroendocrine carcinoma (with 13 mixed with transitional cell carcinoma and 2 with adenocarcinoma). Immunohistochemical study showed positive staining for neuroendocrine markers. On presentation, 1 patient was in stage pT1, 7 in stage pT2, 6 in stage pT3, 2 in stage pT4. Six patients died of the disease after operation. The overall survival was 25 months and the 5-year survival rate was 32.4%. CONCLUSIONS: Small cell neuroendocrine carcinoma of urinary bladder is a highly malignant disease and associated with poor prognosis. The diagnosis relies on detailed histologic examination. Early diagnosis, when coupled with cystectomy or nephroureterectomy and adjuvant chemotherapy, represents the mainstay of management.

[Pathologic diagnosis and differential diagnosis of small cell neuroendocrine carcinoma of kidney].

OBJECTIVE: To study the clinicopathologic features and histologic differential diagnosis of small cell neuroendocrine carcinoma (SmCC) of kidney. METHODS: The clinicopathologic features of 12 cases of SmCC of kidney encountered during the period from 1999 to 2010 were retrospectively reviewed. RESULTS: Six cases of primary and 6 cases of metastatic SmCC involving kidney were identified. Amongst the primary renal SmCC, 2 were located in renal parenchyma and 4 in renal pelvis. Chest X-ray showed negative findings. Five of them underwent radical nephrectomy. On gross examination, the tumor was located centrally around the renal pelvis in 4 cases and peripherally in renal parenchyma in 1 case. On the other hand, 4 of the 6 cases of metastatic SmCC were discovered during therapy for pulmonary SmCC. Two of these patients presented with abdominal pain and gross hematuria, with lung and renal tumor masses identified simultaneously. The diagnosis of all the 6 cases of metastatic SmCC was confirmed by fine needle aspiration biopsy. Microscopically, pure SmCC was demonstrated in the 2 cases of primary renal parenchymal SmCC and 6 cases of metastatic SmCC. The 4 primary renal pelvic SmCC coexisted with urothelial carcinoma component. On immunohistochemical study, all cases were positive for cytokeratin, synaptophysin and CD56. All metastatic cases and 4 primary cases were also positive for TTF-1. Of six patients with primary SmCC two died 4 and 9 months after operation, and two were alive with a follow-up of 25 and 138 months, respectively. Five of six cases with metastatic SmCC died 3 - 8 months after diagnosis. The other 3 cases were failed to follow-up. CONCLUSIONS: Both primary and metastatic SmCC can be found in the kidney. Although rare, primary SmCC is located either in renal parenchyma or in pelvis. The diagnosis of SmCC relies on morphologic examination and immunohistochemical study. TTF-1 immunostaining cannot reliably distinguish primary from metastatic SmCC in kidney. Correlation with clinicoradiologic findings and demonstration of coexisting urothelial carcinoma component (if any) is helpful in delineation of the tumor origin.

[Expression of glypican-3, hepatocyte antigen, alpha-fetoprotein, CD34 and CD10 in hepatocellular carcinoma: a clinicopathologic analysis of 375 cases].

OBJECTIVE: To explore prognostic factors and the expression of glypican-3, hepatocyte antigen (HEP), alpha-fetoprotein (AFP), CD34 and CD10 in hepatocellular carcinoma (HCC) and their prognostic value. METHODS: Clinicopathologic data were analyzed in 375 cases of HCC, in which 80 cases with follow-up were examined by immunohistochemical staining to detect the expression of glypican-3, HEP, AFP, CD34 and CD10 proteins. The relationship between the proteins expression and clinicopathologic features was also evaluated. RESULTS: Tumor number (P = 0.000), tumor size (P = 0.025), tumor differentiation (P = 0.001) and vessel invasion (P = 0.000) were closely related to prognosis of HCC patients; the expression of glypican-3 (66/80,82.5%; P = 0.002), HEP (64/80,80.0%; P = 0.021), AFP (38/80,47.5%; P = 0.014) and CD10 (28/80,35.0%; P = 0.002) was significantly related to tumor differentiation; that of glypican-3 was significantly correlated with tumor number and presence of satellite nodules (P = 0.028) and that of AFP and CD10 was significantly correlated with portal vein thrombi (P = 0.000, P = 0.010). On Kaplan-Meier regression analysis, both low expression of HEP and high expression of AFP were closely related to poor prognosis. CONCLUSIONS: Tumor number, size, differentiation and vessel invasion were important factors affecting the prognosis of patients with HCC. HEP and AFP have prognostic significance in HCC.

A conjugated aptamer-gold nanoparticle fluorescent probe for highly sensitive detection of rHuEPO-α.

We present here a novel conjugated aptamer-gold nanoparticle (Apt-AuNPs) fluorescent probe and its application for specific detection of recombinant human erythropoietin-α (rHuEPO-α). In this nanobiosensor, 12 nm AuNPs function as both a nano-scaffold and a nano-quencher (fluorescent energy acceptor), on the surface of which the complementary sequences are linked (as cODN-AuNPs) and pre-hybridized with carboxymethylfluorescein (FAM)-labeled anti-rHuEPO-α aptamers. Upon target protein binding, the aptamers can be released from the AuNP surface and the fluorescence signal is restored. Key variables such as the length of linker, the hybridization site and length have been designed and optimized. Full performance evaluation including sensitivity, linear range and interference substances are also described. This nanobiosensor provides a promising approach for a simple and direct quantification of rHuEPO-α concentrations as low as 0.92 nM within a few hours.

[CT characteristics of primary salivary gland-type lung cancer].

OBJECTIVE: To improve the diagnostic accuracy of primary salivary gland-type lung cancer on CT. METHODS: The CT findings of 13 pathologically proven primary salivary gland-type lung cancers (mucoepidermoid carcinoma, n = 8, adenoid cystic carcinoma, n = 5) were retrospectively analyzed. RESULTS: Three mucoepidermoid carcinomas were located in the main bronchus, 4 in segmental bronchus, and 1 in peripheral lung. Intrabronchial nodule or mass with smooth or lobulated margin and punctuate or strip calcification (n = 2) was the main CT feature. The tumor showed moderate to significant enhancement after the administration of contrast medium. Three adenoid cystic carcinomas involved trachea, and 2 involved the main and lobular bronchi. The main CT features were diffuse or circumferential irregular thickness of the wall, distorted lumen, and nodule protruding into the lumen, and the longitudinal extent of the tumor was greater than its transverse axis. CONCLUSION: The CT findings of primary salivary gland-type lung cancer are rather specific and may provide helpful information for the clinical diagnosis and treatment.

[Expression of granulocyte colony stimulating factor in patients with non-small cell lung cancer and its clinicopathological significance].

OBJECTIVE: To examine granulocyte colony stimulating factor (G-CSF) expression in human non-small cell lung cancer (NSCLC) as well as discuss its clinicopathological significance. METHODS: Specimens were obtained from 114 cases (53 cases with granulocyte infiltration) diagnosed pathologically as NSCLC in General Hospital of PLA. Paraffin-embedded tissues from these 114 cases of NSCLC were examined for expression of G-CSF by immunohistochemical staining. Correlation between G-CSF expression and pathological features, clinical manifestation, prognosis of patients with NSCLC was analyzed statistically. All the patients were retrospectively followed-up. RESULTS: Fifty-five of the 114 NSCLC specimens expressed G-CSF, and among these 41 (41/54, 75.9%) were large cell carcinoma, nine (9/30, 30.0%) were adenocarcinoma and five (5/30, 16.7%) were squamous cell carcinoma. The expression was significantly correlated with infiltration of tumor mass by neutrophilic granulocytes, histological type, necrosis, differentiation, lymph node metastases, distant metastases, recurrence and survival period (P < 0.01). There was no significant correlation with primary tumor size (P > 0.05). Logistic multi-factor analysis revealed that necrosis, lymph nodes metastases and distant metastases RR (risk ratio) in G-CSF positive group was 5.57, 6.28 and 5.24 times higher than those of G-CSF negative group (P < 0.05). There were remarkable difference of 5-year survival rates (0 and 12.1% respectively) and survival period (42 and 62 months respectively) between positive and negative groups (P < 0.01). CONCLUSIONS: NSCLC with G-CSF excretion are mainly large cell lung cancer. The pathologic characteristics of these cases with G-CSF expression included poor differentiation, remarkable atypia, prominent necrosis and infiltration of tumor mass by neutrophils or emperipolesis. These tumors are usually more aggressive in biological behavior and have worse prognosis than those without G-CSF expression.

Androgen Receptor Splice Variant 7 Predicts Shorter Response in Patients with Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Deprivation Therapy.

BACKGROUND: Whether AR-V7 expression can predict the response in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who receive androgen deprivation therapy (ADT) remains to be explored. OBJECTIVE: To evaluate the predictive value of AR-V7 expression in the prognosis of mHSPC patients receiving ADT. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter prospective cohort study, 310 mHSPC patients commencing ADT were enrolled. Standard immunohistochemical staining was used to assess AR-V7 protein expression in biopsy tissues collected before initiation of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate associations of AR-V7 status (positive vs negative) with progression-free survival (PFS) and overall survival (OS). RESULTS AND LIMITATIONS: Sixty-four (21%) patients were AR-V7-positive and 246 (79%) patients were AR-V7-negative. The median follow-up for patients not confirmed dead was 25 mo (interquartile range 10-30). Compared to AR-V7-negative patients, AR-V7-positive patients had significantly shorter PFS (hazard ratio [HR] 47.39, 95% confidence interval [CI] 25.83-86.94) and OS (HR 3.57, 95% CI 1.46-8.72). In multivariable analysis, AR-V7 was an independent predictive factor (HR 7.61, 95% CI 5.24-11.06) for shorter PFS. Limitations include the sample size and follow-up period. CONCLUSIONS: AR-V7 expression in primary cancer tissue is correlated with poor prognosis for mHSPC patients receiving ADT. PATIENT SUMMARY: In this study of men with metastatic hormone-sensitive prostate cancer, AR-V7 protein expression in primary cancer tissue was associated with poor outcomes on androgen deprivation therapy.