Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC

Port-a-Cath-related complications in 252 patients with solid tissue tumours and the first report of heparin-induced delayed hypersensitivity after Port-a-Cath heparinisation.

The use of the subcutaneous Port-a-Catheters (Port-a-Caths) provides an important mean of venous access for oncological patients. The aim of our retrospective consecutive single-centre study was to investigate Port-a-Cath-related complications in 252 cancer patients. Overall period of Port-a-Caths maintenance was 25 months. The strategy of our centre is to keep Port-a-Caths in situ up to the end of follow-up in adjuvant cancer patients. A total of 22 complications were recorded (8.73%). Interventional complications occurred in four patients. The main complications during Port-a-Cath use included thrombosis (4 patients, 1.58%), infections (4 patients, 1.58%), persistent pain or discomfort (3 patients, 1.19%) and dislocations (2 patients, 0.79%). Median time to the occurrence of any type of complications was 4.5 months. Eleven Port-a-Caths were removed due to complications (4.36%). Similar rate of Port-a-Cath-related thrombosis/infection was seen in adjuvant and advanced cancer patients (no statistical significance). Continuous infusion of anticancer therapy via a Port-a-Cath system is a relatively safe procedure, although major complications might occur. We are first to describe heparin-induced delayed hypersensitivity after heparinisation of Port-a-Cath. This fact should influence the preference to keep the Port-a-Cath after completion of adjuvant anticancer treatment

Second surgery or chemotherapy for relapse after radical resection of colorectal cancer metastases

Purpose: Limited data suggest that second resections for colorectal cancer metastases may improve survival, but no study has compared surgery with chemotherapy in this setting. Therefore, we retrospectively compared the clinical outcome of potentially resectable patients who received a second metastasectomy with those who did not in our single-centre experience. Methods: We retrospectively reviewed the clinical records of all patients treated for metastatic colorectal cancer in our centre over a period of 12 years. We selected patients who relapsed after radical resection of metastases from colorectal cancer and were deemed resectable again by our multidisciplinary team. We then compared the clinical outcome of those who received a second operation with those who refused surgery and also evaluated the role of prognostic factors. Results: We identified 60 patients fulfilling the inclusion criteria. Twenty-nine underwent a second resection and 31 refused surgery. Median overall survival rates were 58.7 and 24.0 months, median times to progression were 14.4 and 6.6 months. Patients who received surgery plus perioperatory chemotherapy (18/29) had a significantly better outcome; 4/29 achieved long-term disease-free survival. Conclusions: Our study suggests that in highly selected metastatic colorectal cancer patients, a multimodal treatment plan, including a second resection, can achieve longer survival with respect to medical therapy