Predicting early recurrence after resection of initially unresectable colorectal liver metastases: the role of baseline and pre-surgery clinical, radiological and molecular factors in a real-life multicentre experience.

BACKGROUND: Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients. MATERIALS AND METHODS: A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery. RESULTS: Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome. CONCLUSIONS: Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.

The Medical and Endovascular Treatment of Atherosclerotic Renal Artery Stenosis (METRAS) study: rationale and study design.

It is unclear whether revascularization of renal artery stenosis (RAS) by means of percutaneous renal angioplasty and stenting (PTRAS) is advantageous over optimal medical therapy. Hence, we designed a randomized clinical trial based on an optimized patient selection strategy and hard experimental endpoints. Primary objective of this study is to determine whether PTRAS is superior or equivalent to optimal medical treatment for preserving glomerular filtration rate (GFR) in the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan. Secondary objectives of this study are to establish whether the two treatments are equivalent in lowering blood pressure, preserving overall renal function and regressing target organ damage, preventing cardiovascular events and improving quality of life. The study is designed as a prospective multicentre randomized, un-blinded two-arm study. Eligible patients will have clinical and angio-CT evidence of RAS. Inclusion criteria is RAS affecting the main renal artery or its major branches either >70% or, if <70, with post-stenotic dilatation. Renal function will be assessed with 99mTc-DTPA renal scintigraphy. Patients will be randomized to either arms considering both resistance index value in the ischemic kidney and the presence of unilateral/bilateral stenosis. Primary experimental endpoint will be the GFR of the ischemic kidney, assessed as quantitative variable by 99TcDTPA, and the loss of ischemic kidney defined as a categorical variable.