Tunica vaginalis testis metastasis as the first clinical manifestation of pancreatic adenocarcinoma: A case report.

BACKGROUND: Metastases from pancreas or ampullary malignancies are common, but the spread to testicle and paratesticular tissue is exceedingly rare. To the best of our knowledge, fewer than 30 cases have been reported in the literature. More rarely, metastasis to tunica vaginalis testis occurs without involvement of the testes and epididymis. CASE SUMMARY: A 65-year-old male who complained of painless swelling of the left scrotum for over 1 wk was referred to the Department of Urology. Scrotal ultrasound showed left testicular hydrocele with paratesticular masses. Chest computed tomography revealed lung metastasis and enlarged left supraclavicular lymph node.The blood tumor markersalpha-fetoprotein, human chorionic gonadotropin, and serum lactate dehydrogenase were withinnormal limits.The preoperative diagnosis was left testicular tumor with lung metastasis. Then radical orchidectomy of the left testicle and high ligation of the spermatic cord were performed, and postoperative histopathology suggested metastatic tumors that was confirmed by an abdominal computed tomographic scan. The positive computed tomography findings, in conjunction with the expression of cytokeratin 7 (CK7), CK20, CK5/6, and absence of expression of Wilms' tumor suppressor gene 1, calretinin, melanocyte, prostate-specific antigen, thyroid transcription factor-1, GATA binding protein 3, caudal type homeobox 2, and napsinA supported the diagnosis of pancreatic adenocarcinoma. The outcome of this patient was unsatisfactory, and he died 3 mo later. CONCLUSION: This case suggests that pancreatic metastatic carcinoma must be considered in the differential diagnosis of scrotal enlargement. The advanced age of the patient wassuggestive of a secondary testicular tumor.In addition, careful physical examination and ultrasonography as well as radiological examination have become a standard modality.

Peptidyl Arginine Deiminase, Type II (PADI2) Is Involved in Urothelial Bladder Cancer.

Peptidyl arginine deiminase, type II (PADI2) expression has been shown to potentiate multiple different carcinogenesis pathway including breast carcinoma and spontaneous skin neoplasia. The objective of this study was to examine the role of PADI2 in urothelial bladder cancer which has not been evaluated previously. Analysis of mutation and genome amplification of bladder cancer within The Cancer Genome Atlas (TCGA) showed that PADI2 is both mutated and amplified in a cohort of bladder cancer patients, with the largest number of mutations detected in urothelial bladder cancer. Even though PADI2 expression was not significantly correlated to survival in bladder cancer patients, it was significantly overexpressed at the mRNA and protein levels, as revealed by TCGA data and immunohistochemistry analysis, respectively. PADI2 showed wide expression pattern in bladder cancer tissues but was hardly detected in tumor adjacent normal tissue. RNAi mediated silencing of PADI2 in the bladder cancer cell line T24 did not result in a change of proliferation. Interestingly knockdown of PADI2 expression did not affect Snail1 protein, which is associated with metastatic progression, in these cells. However, PADI2 silencing remarkably attenuated both in vitro migration and invasion- in T24 cells indicating a Snail1-independent effect of PADI2 on invasive potential of urothelial bladder cancer. This was further corroborated by in vivo xenograft assays where PADI2 shRNA harboring T24 cells did not have detectable tumors by week 4 as compared to robust tumors in the control Luciferase shRNA harboring cells. PADI2 silencing did not affect proliferation rates and hence this would suggest that PADI2 knockdown is perhaps causing increased apoptosis as well as transition through the cell cycle, which needs to be confirmed in future studies. Our results reveal a yet undefined role of PADI2 as an oncogene in urothelial bladder cancer.

Cell Cycle Arrest as a Therapeutic Target of Acute Kidney Injury.

The current lack of complete understanding of the pathogenesis of acute kidney injury (AKI) is a significant barrier to its early diagnosis and treatment. Cell cycle arrest plays an important role in the protection of renal tubular epithelial cells and maladaptive repair following AKI. G1 phase cell arrest serves as a protective mechanism following AKI, avoiding replication of damaged DNA. Insulinlike growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) are closely associated with G1 cell cycle arrest during the very early phase of cellular damage and can serve as an ideal biomarker to predict AKI. However, sustained cell cycle arrest after severe AKI may result in cell senescence and maladaptive repair, with typical characteristics of the development of cell cycle arrest in the gap 2 (G2) or mitotic (M) phase. Markers of cell cycle arrest signal and spread the "alarm" from the site of injury to adjacent cells in an autocrine or paracrine manner, giving rise to abnormal amplification and release of profibrogenic factors, activation of pericytes/perivascular fibroblasts, and eventually fibrosis. Therefore, cell cycle regulation has become a potentially new target for the prevention and treatment of AKI. In this review, we summarize the characteristics of the cell cycle following AKI and the markers of cell cycle arrest that enable the early detection of AKI. We also discuss how to prevent the progression of chronic kidney disease (CKD) by regulating cell cycle arrest.

Macrophages and T lymphocytes are the predominant cells in intimal arteritis of resected renal allografts undergoing acute rejection.

BACKGROUND: In acute renal allograft rejection, T-cell-mediated processes have been generally regarded as dominant. Although there is recent evidence that macrophages play important roles in acute vascular rejection, less is known about the exact proportion of immunocytes in the intimal arteritis of renal allografts with unfavorable outcomes. METHODS: By immunohistochemical staining using nine primary antibodies, we classified the proportions of infiltrating immunocytes in intimal arteritis and glomerulitis in five allografts resected because of acute irreversible graft failure. RESULTS: All five allografts had features of antibody-mediated rejection based on criteria established by the Banff classification. In intimal arteritis, CD3+ T-lymphocytes accounted for 30.6±13.3% of the immunocytes and macrophages for 40.4±9.2%. 45.4% of the T-cells were CD8+ cytotoxic T-cells. Neutrophils were also present but accounted for a relatively low proportion of the cells (8.8±8.6%). B-cells and plasma cells all accounted for <5% of the immunocytes. NK cells were readily detected (4.2±4.2%). When we compared types of arteritis, the CD15+ neutrophils accounted for as many as 27.8±15.1% of immunocytes in V3 vasculitis and only 1.0±1.4% in V2 vasculitis. CD3+ T-lymphocytes accounted for 25.8±7.3% of immunocytes in V3 vasculitis and 41.5±7.9% in V2 vasculitis. In glomerulitis, the immunocytes were mainly macrophages (53.1±9.1%) and neutrophils (34.6±9.9%). CONCLUSION: Macrophages and T-lymphocytes accounted for the highest percentage of immunocytes in the intimal arteritis of irreversible renal failure associated with antibody-mediated rejection. 45.4% of the T-cells were CD8+ cytotoxic T-cells. Neutrophils and NK cells were also present in these lesions. The proportion of neutrophils in V3 vasculitis was much higher than in V2 vasculitis. These observations suggest that besides macrophages and T-lymphocytes, neutrophils may also play a role in the more severe arterial lesion. To our knowledge this is the first report of this observation. Macrophages and neutrophils were the main inflammatory cells in the glomerulitis of acute rejection.