Helicase Hmi1 stimulates the synthesis of concatemeric mitochondrial DNA molecules in yeast Saccharomyces cerevisiae

Hmi1p is a helicase in the yeast Saccharomyces cerevisiae required for maintenance of the wild-type mitochondrial genome. Disruption of the HMI1 ORF generates ^– and ⁰ cells. Here we demonstrate that, in ^– yeast strains, Hmi1p stimulates the synthesis of long concatemeric mitochondrial DNA molecules associated with a reduction in the number of nucleoids used for mitochondrial DNA packaging. Surprisingly, the ATPase negative mutants of Hmi1p can also stimulate the synthesis of long concatemeric ^– mitochondrial DNA molecules and support the maintenance of the wild-type mitochondrial genome, albeit with reduced efficiency. We show that, in the mutant hmi1–5 background, the wild-type mitochondrial DNA is fragmented; and we propose that, in hmi1 yeast cells, the loss of the wild-type mitochondrial genome is caused by this fragmentation of the mitochondrial DNA.     

Treatment of renal angiomyolipoma: pooled analysis of individual patient data

Epididymal anomalies and patent processus vaginalis are frequently found in boys with cryptorchidism or hydrocele. We conducted this study to evaluate the association between epididymal anomalies and testicular location or patent processus vaginalis in boys with undescended testis or hydrocele. Children undergoing surgery with undescended testis (group A, 136 boys and 162 testes) or communicating hydrocele (group B, 93 boys and 96 testes) were included. Testicular locations and epididymal anomalies were investigated prospectively. An anomalous epididymis was defined as anomalies of epididymal fusion that consisted of loss of continuity between the testis, the epididymis, and the long looping epididymis. The epididymis was considered normal when a normal, firm attachment between the testis, the caput, and the cauda epididymis was present. The mean ages of groups A and B were 24.6 ± 19.7 (range, 8–52 months) and 31.4 ± 20.6 months (range, 10–59 months). The incidence of epididymal anomalies was significantly higher in group A than that in group B (65.4 % vs. 13.5 %, P < 0.001). The incidence of epididymal anomalies in boys with undescended testis was significantly different according to testis location. Epididymal anomalies were observed in 100 %, 91.4 %, and 39.3 % of cases when the testis was located in the abdomen, inguinal canal, and distal to the external inguinal ring, respectively (P < 0.001). We conclude that epididymal anomalies were more frequent in boys with undescended testis than in boys with hydrocele, and that these anomalies were more frequent when undescended testis was at a higher level. These results suggest that testicular location is associated with epididymal anomalies rather than patent processus vaginalis.     

European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update

Context

The European Association of Urology Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC.

Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer

Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment. These therapies are based on treatment with antibodies that block programmed cell death-1 (PD-1), programmed cell death ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved survival in several tumour types. So far, nivolumab is the only approved anti-PD-1 monoclonal antibody after VEGF therapy in mRCC. According to preclinical and clinical studies, combination therapies with VEGF- and checkpoint inhibitors have synergistic effect achieving improved response rates. However, toxicity in some combinations is high. In this article, we present a review of the ongoing trials with these drug combinations for RCC.     

Bilateral and multifocal phyllodes tumours of the breast: A case report

Phyllodes tumours are rare breast neoplasms that present as painless breast masses. They are classified as benign, malignant and borderline. More rare presentations of these tumours include bilateral asynchronous disease and unilateral multifocal disease. Surgical excision with clear margins remains the treatment of choice for these tumours. The present case report is the first to be discussed in the literature. It describes a patient presenting with synchronous bilateral, multifocal breast phyllodes tumours who underwent immediate reconstruction with tissue expanders at the time of her mastectomies.     

Routine shave margins are not necessary in early stage breast cancer treated with Breast Conserving Surgery

Introduction

Breast Conserving Surgery (BCS) is considered standard of care for women with early stage breast cancer. Between 20 and 50% of women treated with BCS will require re-operation for positive or close margins and it has been suggested that routine cavity shave margins may reduce the frequency of positive margins.

Excision of breast fibroepithelial lesions: when is it still necessary?—A 10-year review of a regional centre

Breast Cancer Research and Treatment - Fibroepithelial lesions (FEL) range from benign fibroadenoma (FA) to malignant phyllodes tumor (PT), but can be difficult to diagnose on core needle biopsy...     

Follow-up after curative treatment of localised renal cell carcinoma

Purpose

Patients with localised renal cell carcinoma (RCC) receiving curative surgery, either radical or partial nephrectomy, have been shown in contemporary studies to develop recurrence within 5 years in 20–30% of case. Therefore, post-operative follow-up (FU) imaging plays a crucial role in detecting recurrent or metastatic disease. A number of prognostic scores have been developed to predict risk of recurrence. This review summarises the current knowledge on established FU protocols and their limitations.

Methods

A non-systematic literature search was conducted using Medline. Furthermore, major guidelines [European Association of Urology (EAU), American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN)] were reviewed and assessed.

Results

The EAU, AUA and NCCN post-operative follow-up guidelines differ in the frequency and type of imaging modalities recommended. The optimal duration of follow-up remains to be elucidated as does the impact of follow-up protocols on patient outcomes and quality of life. Established follow-up protocols do not take non-RCC-related factors, such as patient age and performance status into account. However, in the future individualised duration of FU based on competing risks of cancer recurrence and non-RCC death may be optimised, maximising resources and patient quality of life.

Conclusion

There is a clear need to establish evidence-based follow-up protocols and to assess the impact of follow-up protocols on individual patients and society.

     

De-Escalating Breast Cancer Surgery: Should We Apply Quality Indicators from Other Jurisdictions in Canada?

Quality Indicators (QIs), including the breast-conserving surgery (BCS) rate, were published by the European and American Breast Cancer Societies and this study assesses these in a Canadian population to look for opportunities to de-escalate surgery. A total of 2311 patients having surgery for unilateral, unifocal breast cancer between 2013 and 2017 were identified and BCS QIs calculated. Reasons for mastectomy had been prospectively collected with synoptic operative reporting. Our BCS rate for invasive cancer < 3 cm was 77.1%, invasive cancer < 2 cm was 84.1%, and DCIS < 2 cm was 84.9%. There was no statistically significant change in BCS rates over a five-year period, but there was a reduction in contralateral prophylactic mastectomies (CPM) from 28% in 2013 to 16% in 2017 (p < 0.001). Trend analysis looking at tumour size and medical need for mastectomy indicated that 80% of patients at our centre would be eligible for BCS with tumour cut off of 2.5 cm. Our institution met American but not European QI standards for BCS rates, potentially indicating a difference in patient demographics compared to Europe. Our results support the understanding that BCS rates are influenced by multiple factors and are challenging to compare across jurisdictions. CPM rates may offer a more actionable opportunity to de-escalate surgery for breast cancer.