Case Report: Step-by-step procedures for total intracorporeal laparoscopic kidney autotransplantation in a patient with distal high-risk upper tract urothelial carcinoma

A 47-year-old man presented to the emergency department with right abdominal pain and a new onset of painless haematuria two weeks earlier. Urine cytology test results suggested urothelial carcinoma. Computed tomography urography (CTU) showed a filling defect in the lower right ureter with right hydronephrosis. Lymphadenopathy and any signs of metastatic disease were absent on CTU. Cystoscopy appeared normal. Creatinine level was also normal before surgery. After the treatment options were discussed, the patient chose to undergo 3D total intracorporeal laparoscopic kidney autotransplantation, bladder cuff excision, and segmental resection of the proximal two-thirds of the ureter based on the membrane anatomy concept. After more than one year of follow-up, the patient was in good health and showed no signs of haematuria. Surveillance cystoscopy and CTU examination showed no evidence of disease recurrence. Therefore, it is reasonable to assume that kidney-sparing surgery may be considered for carefully selected patients with high-grade upper tract urothelial carcinoma

mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer

Ribonucleotide reductase (RNR) is the key enzyme that catalyzes the production of deoxyribonucleotides (dNTPs) for DNA replication and it is also essential for cancer cell proliferation. As the RNR inhibitor, Gemcitabine is widely used in cancer therapies, however, resistance limits its therapeutic efficacy and curative potential. Here, we identified that mTORC2 is a main driver of gemcitabine resistance in non-small cell lung cancers (NSCLC). Pharmacological or genetic inhibition of mTORC2 greatly enhanced gemcitabine induced cytotoxicity and DNA damage. Mechanistically, mTORC2 directly interacted and phosphorylated RNR large subunit RRM1 at Ser 631. Ser631 phosphorylation of RRM1 enhanced its interaction with small subunit RRM2 to maintain sufficient RNR enzymatic activity for efficient DNA replication. Targeting mTORC2 retarded DNA replication fork progression and improved therapeutic efficacy of gemcitabine in NSCLC xenograft model in vivo. Thus, these results identified a mechanism through mTORC2 regulating RNR activity and DNA replication, conferring gemcitabine resistance to cancer cells

Diagnostic Performance of Fas Ligand mRNA Expression for Acute Rejection after Kidney Transplantation: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>The value of Fas ligand (FASL) as a diagnostic immune marker for acute renal rejection is controversial; this meta-analysis aimed to clarify the role of FASL in acute renal rejection.</p><p>Methods</p><p>The relevant literature was included by systematic searching the MEDLINE, EMBASE, and Cochrane Library databases. Accuracy data for acute rejection (AR) and potential confounding variables (the year of publication, area, sample source, quantitative techniques, housekeeping genes, fluorescence staining, sample collection time post-renal transplantation, and clinical classification of AR) were extracted after carefully reviewing the studies. Data were analyzed by Meta-DiSc 1.4, RevMan 5.0, and the Midas module in Stata 11.0 software.</p><p>Results</p><p>Twelve relevant studies involving 496 subjects were included. The overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio, together with the 95% CI were 0.64 (0.57–0.70), 0.90 (0.85–0.93), 5.66 (3.51–9.11), 0.30 (0.16–0.54), and 30.63 (14.67–63.92), respectively. The area under the summary receiver operating characteristic curve (AUC) was 0.9389. Fagan’s nomogram showed that the probability of AR episodes in the kidney transplant recipient increased from 15% to 69% when FASL was positive, and was reduced to 4% when FASL was negative. No threshold effect, sensitivity analyses, meta-regression, and subgroup analyses based on the potential variables had a significant statistical change for heterogeneity.</p><p>Conclusions</p><p>Current evidence suggests the diagnostic potential for FASL mRNA detection as a reliable immune marker for AR in renal allograft recipients. Further large, multicenter, prospective studies are needed to validate the power of this test marker in the non-invasive diagnosis of AR after renal transplantation.</p></div

Deeks’ funnel plot for the assessment of potential bias in FasL analysis.

<p>Deeks’ funnel plot for the assessment of potential bias in FasL analysis.</p

Diagnostic accuracy of FasL for AR after kidney transplantation.

<p>Diagnostic accuracy of FasL for AR after kidney transplantation.</p

Basic information extracted from the eligible studies.

<p>Basic information extracted from the eligible studies.</p

The Fagan's nomograms and post-test probability of FasL detection for developing AR.

<p>The Fagan's nomograms and post-test probability of FasL detection for developing AR.</p

Study search flow for meta-analysis.

<p>Study search flow for meta-analysis.</p

SROC plot of FasL test for AR diagnosis in subgroups analyses.

<p>(A), the year of publication; (B), sample; (C), area; (D), PCR technique; (E), housekeeping gene; (F), fluorescence staining; (G), clinical classification of AR.</p

Diagnostic performance of FasL for AR.

<p>Forest plots of overall sensitivity(A), specificity(B), positive likelihood ratio (LR)(C), negative LR(D), diagnostic odds ratio (OR) (E), and SROC curve (F).</p