Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors.MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed.Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n = 9), bladder tumor (n = 7), testis tumors (n = 4), and prostate cancer (n = 2). There was no intraoperative complication. Postoperative complications were seen in 2 patients.ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.     

Aprepitant exerts anti-fibrotic effect via inhibition of TGF-β/Smad3 pathway in bleomycin-induced pulmonary fibrosis in rats

Bleomycin is a well-recognized antineoplastic drug. However, pulmonary fibrosis (PF) is considered to be the principal drawback that greatly limits its use. Here, we sought to investigate ability of the neurokinin receptor 1 blocker, aprepitant, to prevent PF caused by bleomycin. Male adult Wistar rat groups were given a single intratracheal injection of bleomycin, either alone or in combination with aprepitant therapy for 3 or 14 days. Collagen deposition and a rise in transforming growth factor beta (TGF-β) immunoreactivity in lung tissue serve as evidence of bleomycin-induced PF. The serum levels of lactate dehydrogenase, alkaline phosphatase, and total antioxidant improved after aprepitant therapy.Additionally, it reduced the protein expressions of interferon alpha, tumor necrosis factor alpha, and lung lipid peroxidation. Moreover, aprepitant treatment led to an increase in the antioxidant indices glutathione, glutathione peroxidase, and catalase. Aprepitant is postulated to protect against bleomycin-induced PF by decreasing TGF-β, phosphorylating Smad3, and increasing interleukin 37, an anti-fibrotic cytokine, and G Protein-coupled Receptor Kinase 2. Aprepitant for 14 days considerably exceeded aprepitant for 3 days in terms of improving lung damage and having an anti-fibrotic impact. In conclusion, aprepitant treatment for 14 days may be used as an adjuvant to bleomycin therapy to prevent PF, mostly through inhibiting the TGF-/p-Smad3 fibrotic pathway.     

Volume and function of the operated kidney after nephron-sparing surgery for unilateral renal tumor

Aim

We sought to assess the magnitude of functional decline and the natural history of the operated kidney residual function after zero-ischemia nephron-sparing surgery (Z-NSS) in children with unilateral renal tumor (URT).

Sinonasal tract pathology: an updated review of select entities

The sinonasal tract is host to numerous benign and malignant entities that can pose diagnostic challenges to pathologists as a result of limited exposure in daily practice. This review concentrates on certain key characteristics of select entities with focus on differential diagnosis, novel subtypes and/or molecular distinction. The aim of this review is to summarize current knowledge and shed light on diagnostically challenging and emerging entities in sinonasal tract pathology.     

In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

Feasibility and safety of irreversible electroporation (IRE) in patients with small renal masses: Results of a prospective study

Background

Irreversible electroporation (IRE) has the potential to overcome limitations of thermal ablation, enabling small renal mass (SRM) ablation near vital structures.

Updated Clinical Practice Guideline on Use of Gadolinium-Based Contrast Agents in Kidney Disease Issued by the Canadian Association of Radiologists

In 2017, the Canadian Association of Radiologists issued a clinical practice guideline (CPG) regarding the use of gadolinium-based contrast agents (GBCAs) in patients with acute kidney injury (AKI), chronic kidney disease (CKD), or on dialysis due to mounting evidence indicating that nephrogenic systemic fibrosis (NSF) occurs with extreme rarity or not at all when using Group II GBCAs or the Group III GBCA gadoxetic acid (compared to first generation Group I linear GBCAs). One of the goals of the work group was to re-evaluate the CPG after 24 months to determine the effect of more liberal use of GBCA on reported cases of NSF in patients with AKI, CKD Stage 4 or 5 (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²), or those that are dialysis-dependent. A comprehensive review of the literature was conducted by a subcommittee of the initial CPG panel between the dates of January 1, 2017-December 31, 2018 to identify new unconfounded cases of NSF linked to Group II or Group III GBCAs and an updated CPG developed. To our knowledge, when using a Group II or Group III GBCA between 2017-2018, only a single unconfounded case report of a fibrosing dermopathy has been reported in a patient who received gadobenate dimeglumine with Stage 2 CKD. No other unconfounded cases of NSF have been reported with Group II or III agents in during this timeframe. The subcommittee concluded that the main recommendations from the 2017 CPG should remain unaltered, but agreed that screening for renal disease in the outpatient setting is no longer justifiable, cost-effective or recommended. Patients on hemodialysis (HD) should, however, be identified prior to GBCA administration to arrange timely HD to optimize gadolinium clearance, although there remains no evidence that HD reduces the risk of NSF. When administering Group II or III GBCAs to patients with AKI, on dialysis or with severe CKD, informed consent relating to NSF is also no longer explicitly recommended.     

Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P < .01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes.