Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.

BackgroundIn a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years.MethodsPatients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan–Meier method.ResultsFollow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0–9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5–9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence.ConclusionsLong-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years.

Background: Selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants used in first-world countries and are generally well tolerated. Specifically, less cardiovascular toxicity has been reported in comparison with tricyclic antidepressants. Here we report QT interval prolongation after an overdose of the SSRI sertraline.

Metastatic rectal cancer patients could benefit from novel therapeutic approaches. The signaling network formed by chemokines and their receptors can promote metastasis and resistance to current anticancer treatments. This study assessed the expression of chemokine receptor 4 (CXCR4) and its ligand CXCL12 immuhistochemically in stage IV rectal tumors. Paraffin-embedded primary tumor collected before and after local radiotherapy and systemic treatment with bevacizumab, oxaliplatin and capecitabine was analyzed. Receptor and ligand expression was assessed in the cytoplasm and nucleus of tumor, stromal and normal rectal crypt cells. Baseline expression of CXCR4 and CXCL12 was correlated with patients' pathologic response to treatment. At diagnosis (n=46), 89% of the rectal tumors expressed cytoplasmic CXCR4 and 81% CXCL12. Nuclear CXCR4 expression in tumor cells was present in 30% and nuclear CXCL12 expression in 35% of the tumors. After radiochemotherapy and administration of bevacizumab, nuclear CXCL12 expression was observed in 79% of residual tumors, as compared to 31% of the paired tumor samples expressing nuclear CXCL12 before treatment (P=0.001). There were no differences in CXCR4 or CXCL12 expression at baseline between the patients who had (n=9) and did not have (n=30) a pathologic complete response. Our results show that CXCR4 and CXCL12 are extensively expressed in primary rectal tumors of patients presenting with metastatic disease, while radiochemotherapy and bevacizumab further upregulate CXCL12 expression. These data indicate the importance of the CXCR4/CXCL12 axis in rectal tumor biology, and may suggest the CXCR4/CXCL12 receptor-ligand pair as a potential therapeutic target in metastatic rectal cancer.