Positive KI67 and periodic acid-schiff mandates wider range of excision in scrotal extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) of the scrotum is a rare disease that requires surgical excision. A positive margin is related to recurrence and poorer prognosis. We aimed to investigate the expression of Ki67 and periodic acid-Schiff (PAS) in a biopsy sample and to evaluate their predictive value in true margin status. METHODS: Sixty-four patients with noninvasive scrotal EMPD were included. Immunohistochemical staining of Ki67 and PAS was reviewed and compared statistically with the margin status of intraoperative frozen section examination (FSE). RESULTS: Seventeen of 64 patients had a positive margin discovered at the first FSE. Expression of Ki67 was not significantly different between positive and negative margin status (p = .16). Expression of PAS was higher in samples with positive margins (p = .05). The incidence of positive margins was significantly higher in the double-positive group than in the double-negative group (p = .03). CONCLUSION: Positive expression of both factors in a biopsy sample requires wider excision to ensure negative margins.

Med19 promotes bone metastasis and invasiveness of bladder urothelial carcinoma via bone morphogenetic protein 2.

Bladder cancer (BCa) remained a major health problem. Med19 was related to tumor growth of BCa. Bone morphogenetic proteins (BMPs) were reported to be critical in bone metastasis of cancer. We therefore investigated the relations between Med19 and BMPs in BCa and their effect on bone metastasis of BCa. Bladder cancer cell lines were cultured and interfered with Med19 shRNA and control. Expressions of BMP-1, BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-9, and BMP-15 were studied between 2 groups. Fifty-two BCa samples were included for immunohistochemical staining of Med19 and BMP-2. Expressions were scored and studied statistically. Invasiveness was studied with Transwell assay. Silencing or Med19 in BCa cells induced altered expressions of BMPs. Increased expressions of BMP-1, BMP-4, BMP-6, BMP-7, and BMP-15 and decreased expressions of BMP-2, BMP-5, and BMP-9 were noticed, but only BMP-2 reached statistical significance. Expressions of Med19 and BMP-2 were significantly higher in cases with bone metastasis and were positively correlated in cases with bone metastasis and muscle invasion. Med19 is a critical factor involved in the invasiveness and promotion of bone metastasis of BCa, possibly via BMP-2.

Low local metastatic rate may widen indication of nephron-sparing surgery for renal cell carcinoma.

To explore the rationale for renal-sparing surgery as an alternative method to radical nephrectomy in the treatment of renal cell carcinoma (RCC), we analyzed clinical data from 94 patients diagnosed as having RCC. They were divided into 3 groups based on the maximum diameter of their tumor specimens. Group A had tumors size ranging from 0 to 4 cm, group B had tumors size ranging from 4 to 7 cm, and group C had tumors size greater than 7 cm. Tissue samples (5 cm) were taken from the upper pole side, lower pole side, and renal pelvic side of the tumor pseudocapsule; if the tumor was located on 1 pole of the kidney, samples were collected from 2 directions. The specimens were then embedded in paraffin and cut serially at segments 0 to 1, 1 to 3, and 3 to 5 cm. Staining with hematoxylin and eosin, anti-pancytokeratin, and vimentin was performed to determine tumor type and tumor infiltration. From the 94 patients analyzed, 2 patients in group A had RCC metastasis within 1 cm of tissue around the pseudocapsule, and 4 patients in groups B and C had lymph node metastasis without metastasis in the tissue 1 cm outside the pseudocapsule in all 3 directions described. There was no statistical significant difference found between the incidence of local metastasis of the various tumor sizes, suggesting that local metastasis of RCC is not associated with the size of the tumor. Based on the observation that incidences of local metastasis were low in early-stage RCC, we came to the conclusion that pseudocapsule of RCC tumor might have growth-limiting effect on the tumor enclosed. It is theoretically a safer and better surgical option for patients with RCC with a smaller size of tumor and indications for radical nephrectomy to undergo renal-sparing surgery with an excision margin of 1 cm of normal tissue around the pseudocapsule of the tumor.

Prostate Health Index (phi) and its derivatives predict Gleason score upgrading after radical prostatectomy among patients with low-risk prostate cancer.

To analyze the performance of the Prostate Health Index (phi) and its derivatives for predicting Gleason score (GS) upgrading between prostate biopsy and radical prostatectomy (RP) in the Chinese population, an observational, prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020. Pathological reclassification was determined by the Gleason Grade Group (GG). The area under the receiver operating characteristic curve (AUC) and logistic regression (LR) models were used to evaluate the predictive performance of predictors. In clinically low-risk patients with biopsy GG ≤2, phi (odds ratio [OR] = 1.80, 95% confidence interval [95% CI]: 1.14-2.82, P = 0.01) and its derivative phi density (PHID; OR = 2.34, 95% CI: 1.30-4.20, P = 0.005) were significantly associated with upgrading to GG ≥3 after RP, and the results were confirmed by multivariable analysis. Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG≥2. Compared to the base model (AUC = 0.59), addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients (AUC = 0.69 and 0.71, respectively, both P < 0.05). In conclusion, phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

Elevated serum soluble Fas ligand is a promising marker of testicular toxicity induced by epirubicin in rats.

To investigate the role of the Fas/Fas ligand (Fas/FasL) system in testicular toxicity induced by epirubicin (Epi) and to correlate the system with the serum levels of soluble Fas and Fas ligand (sFas/sFasL), epirubicin was intraperitoneally administered to male Sprague-Dawley male rats at doses of 1.2mg/kg once a week for 10 weeks, and genital organ weights and histopathology were examined. Fas and FasL expression in rat testis were examined by immunohistochemistry. Apoptosis was assessed by TUNEL assay. Expression levels of Fas and FasL were analyzed by RT-PCR and Western blotting. Serum sFas/sFasL levels were determined by ELISA. The results show that the testicular toxicity of Epi involved germ cell apoptosis. Fas and FasL protein expression levels were markedly increased in Epi-treated rat testes, as was expression of sFasL. In particular, increasing serum sFasL levels were positively correlated with elevated expression levels of FasL and sFasL in the testes of Epi-treated rats, revealing serum sFasL to be a promising marker of testicular toxicity after cytotoxic chemotherapy.

[Diagnosis of testicular cancer: review of 47 cases].

OBJECTIVE: To improve the diagnostic level of testicular cancer by a retrospective review of 47 cases. METHODS: The symptoms, signs, imaging studies, tumour markers and histological diagnoses of 47 cases were reviewed. RESULTS: The mass in testes was palpated in all patients. As a useful tool in the diagnosis of testicular cancer, scrotal ultrasonography had a detecting sensitivity over 90%. Though sensitive to retroperitoneal lymph nodes, CT had a certain level of false positive rate. Tumor markers, especially AFP, were significantly useful in the diagnosis and prognosis of testicular cancer. Histological examination showed 27 cases of seminoma, 7 cases of embryonal carcinoma, 6 cases of teratoma, 3 cases of lymphoma, 1 case of spermatocytic seminoma and 1 case of sarcoma. CONCLUSION: Patient self-examination is extremely helpful for an earlier diagnosis. Ultrasonography and CT are invaluable in the diagnosis and staging of testicular cancer. Playing key roles in the diagnosis and prognosis of testicular cancer, tumour markers should be routinely examined.

[Extramammary Paget's disease of the scrotum: report of 79 cases].

OBJECTIVE: To investigate the clinicopathologic feature and treatment result as well as prognosis of Paget's disease of the scrotum. METHODS: The data of 79 patients with Paget's disease of the scrotum confirmed pathologically from 1993 to 2004 were retrospectively analyzed. The median age of these patients was 62.3 years. The median duration of the disease was 3 years and 7 months. Locally extensive excision and intra-operative frozen section analysis of resection margin were performed in 78 patients. Inguinal and iliac radical lymphadenectomy was done in 7 patients with inguinal lymph node metastasis. RESULTS: Local recurrence developed in 9 patients, and 3 patients died of the disease during follow-up. CONCLUSION: The prognosis of Paget's disease of the scrotum after surgical resection is good. To highly watch out for the disease, to perform histological examination and surgical resection as early as possible are keys to control it successfully.

[Expression and significance of steroid 5alpha-reductase isoenzymes in benign hyperplastic prostate tissues].

OBJECTIVE: To study the expression levels and cell-specific expression patterns of steroid 5alpha-reductase type 1 and type 2 isoenzymes in human benign prostatic hyperplasia (BPH) tissues. METHODS: Immunohistochemistry and RT-PCR were used to investigate qualitatively and semi-quantitatively the expression of 5alpha-reductases type 1 and type 2 in 15 specimens of normal prostate tissues from dead kidney donor or patients undergoing cystectomy and 25 BPH tissues obtained from suprapubie enucleation. RESULTS: Both steroid 5alpha-reductase type 1 mRNA and protein and 5alpha-reductase type 2 mRNA and protein were present in the normal and BPH tissues, especially in the glandular epithelial cells and mainly in the cytoplasm. In the BPH group the expression of type 2 reductase in the periurethral tissues was significant higher than that in the subcapsular tissues (1.50 +/- 0.42 vs. 1.07 +/- 0.35, P < 0.01), however, there was no significant difference in the expression of type 1 reductase between these 2 zones (P > 0.05). The expression level of 5alpha-reductase type 2 mRNA in BPH tissues was significantly higher than that in the normal specimens (e.g. in periurethral zone 1.50 +/- 0.42 vs. 0.98 +/- 0.32, P < 0.01), but there was no statistically significant difference in the expression of 5alpha-reductase type 1 mRNA between these 2 groups (e.g. in periurethral zone 0.62 +/- 0.31 vs 0.51 +/- 0.24, P > 0.05). In BPH tissues, the expression of type 2 mRNA was significantly higher in the larger prostate tissues (>or= 40 g) than in the smaller ones (e.g. in periurethral zone 1.58 +/- 0.47 vs. 1.14 +/- 0.46, P < 0.05), however, there was no significant difference in the expression of 5alpha-reductase type 1 mRNA between the BPH tissues with different volumes. CONCLUSION: Type 2 5alpha-reductase plays an important role in the pathogenesis and maintenance of BPH. The role of type 1 expression in the pathogenesis of BPH needs further research.

Paraneoplastic symptoms: cachexia, polycythemia, and hypercalcemia are, respectively, related to vascular endothelial growth factor (VEGF) expression in renal clear cell carcinoma.

OBJECTIVES: To evaluate whether there is a relation between expression of vascular endothelial growth factor (VEGF) and any of the paraneoplastic syndromes (PNS) in clear cell renal cell carcinoma (ccRCC) patients. MATERIALS AND METHODS: A total of 667 patients with ccRCC and at least one PNS were included. Thorough history taking, physical examinations, and laboratory tests were used to diagnose PNS. Immunohistochemistry was performed for VEGF evaluation. RESULTS: There were 10 different PNS identified in the population. Sixty patients had a single paraneoplastic presentation. In all patients, presence of cachexia (n = 267, P < 0.0001), polycythemia (n = 40, P = 0.0014), and hypercalcemia (n = 48, P = 0.0006) was correlated to VEGF expression. Correlation was neither acquired in Stauffer's syndrome, pyrexia, elevated erythrocyte sedimentation rate (ESR), anemia, thrombocytosis, hypertension, neuromyopathy nor obtained within patients with single PNS. CONCLUSIONS: Relations between PNS and VEGF expression in renal cell carcinoma (RCC) has not been studied yet. The results we gained hereby can help us further understand the mechanistic of PNS in RCC.

Population study of genetic polymorphisms and superficial bladder cancer risk in Han-Chinese smokers in Shanghai.

BACKGROUND: We investigated the association between the polymorphisms of DNA repair genes, metabolic enzyme genes, and superficial bladder cancer to better understand the role of gene polymorphisms in bladder carcinogenesis for the Han-Chinese population in Shanghai. METHODS: The SNPs in the XPC, XPG, XRCC1, NQO2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 genes were genotyped using the TaqMan Probe-based polymerase chain reaction. RESULTS: The AC + CC genotypes of XPC Lys939Gln and the CC genotype of XPG His1104Asp were more frequent in patients of superficial bladder cancer at the initial diagnosis (adjusted OR [95% CI], 1.89 [1.21-3.24]; adjusted OR [95% CI], 1.07 [0.86-1.87], respectively). The risk for carriers of the XPC-33512C allele increased after stratifying by smoking habits (adjusted OR [95% CI], 1.95 [0.56-6.09]). There was a significant trend for an increased carcinogenesis risk with an increasing number of putative high-risk alleles. We found no significant associations between any of the ten polymorphisms and clinicopathological features of superficial bladder cancer. CONCLUSION: These results suggest that the polymorphism in XPC Lys939Gln may modulate superficial bladder cancer risk, and these effects may preferentially affect current smokers. The data also support the possibility of an increased risk for superficial bladder cancer in individuals with a higher number of genetic variations in DNA repair and metabolic enzyme genes.