An update on irreversible electroporation of liver tumours.

OBJECTIVE. To investigate the clinical efficacy and safety of irreversible electroporation for ablation of liver tumour in humans. DATA SOURCES. The PubMed and MEDLINE databases were systematically searched. STUDY SELECTION. Clinical research published in English in the last 10 years until October 2013 that address clinical issues related to irreversible electroporation of human liver tumours were selected. "Liver tumor", "local ablative therapy", and "irreversible electroporation" were used as the search terms. DATA EXTRACTION AND SYNTHESIS. The data extracted for this review was analysed by the authors, with a focus on the clinical efficacy and the safety of irreversible electroporation. The complete response rates look promising, ranging from 72% to 100%, except in one study in a subgroup of liver tumours in which the complete response rate was only 50% that was likely due to the inclusion of larger-size tumours. In one study, the local recurrence rate at 12 months was approximately 40%. As for the safety of irreversible electroporation, there were only a few reported complications (cardiac arrhythmia, pneumothorax, and electrolyte disturbance) that were mostly transient and not serious. There was no reported mortality related to the use of irreversible electroporation. CONCLUSION. Irreversible electroporation is a potentially effective liver tumour ablative therapy that gives rise to only mild and transient side-effects. Further studies with better patient selection criteria and longer follow-up are needed to clarify its role as a first-line liver tumour treatment modality.

Critical roles of ring finger protein RNF8 in replication stress responses.

Histone ubiquitylation is emerging as an important protective component in cellular responses to DNA damage. The ubiquitin ligases RNF8 and RNF168 assemble ubiquitin chains onto histone molecules surrounding DNA breaks and facilitate retention of DNA repair proteins. Although RNF8 and RNF168 play important roles in repair of DNA double strand breaks, their requirement for cell protection from replication stress is largely unknown. In this study, we uncovered RNF168-independent roles of RNF8 in repair of replication inhibition-induced DNA damage. We showed that RNF8 depletion, but not RNF168 depletion, hyper-sensitized cells to hydroxyurea and aphidicolin treatment. Consistently, hydroxyurea induced persistent single strand DNA lesions and sustained CHK1 activation in RNF8-depleted cells. In line with strict requirement for RAD51-dependent repair of hydroxyurea-stalled replication forks, RNF8 depletion compromised RAD51 accumulation onto single strand DNA lesions, suggesting that impaired replication fork repair may underlie the enhanced cellular sensitivity to replication arrest observed in RNF8-depleted cells. In total, our study highlights the differential requirement for the ubiquitin ligase RNF8 in facilitating repair of replication stress-associated DNA damage.

Operating on a suspicious lung mass without a preoperative tissue diagnosis: pros and cons.

OBJECTIVES: Patients with a suspicious lung mass sometimes receive surgery with no preoperative tissue diagnosis despite-and sometimes in lieu of-modern medical investigations. The pros and cons of doing so have rarely been studied. METHODS: Pulmonary surgery was performed in 443 consecutive adult patients with a lung mass confirmed or suspected to be an early stage primary lung cancer. No diagnosis was confirmed preoperatively in 206 (46.5%) patients. Whether to take a core biopsy or wedge excision biopsy for frozen section assessment intraoperatively was decided at the surgeon's discretion. RESULTS: Patients without preoperative diagnosis were on average younger than those with a diagnosis (61 vs 66 years, P < 0.01), but were otherwise similar to those who had a preoperative diagnosis confirmed. In all patients operated on without a preoperative diagnosis, there was no mortality or major complication, and the perioperative minor morbidity rate was 9.7%. Among patients ultimately found to have lung cancer and who received a lobectomy, performing a frozen section intraoperatively did not increase mean operation time or morbidity. Among those patients with no preoperative tissue diagnosis, 97 (47.1%) proceeded to surgery without attempts at preoperative diagnosis, and 109 (52.9%), after attempts at preoperative diagnosis failed to yield a positive diagnosis. After surgery, benign disease was found in 16 (7.8%) patients without preoperative diagnosis. A significantly lower proportion of patients without preoperative diagnosis waited an interval of over 28 days between presentation and being accepted for thoracic surgery (42.2 vs 54.9%, P < 0.01). However, they were not more likely to have Stage I disease and did not have better recurrence-free survival rates on survival analysis. CONCLUSIONS: Proceeding to surgery without preoperative diagnosis in selected patients with a suspicious lung mass is safe and can potentially reduce the interval between presentation and surgical management. However, the shortened workup time is not associated with improved surgical or oncological outcomes.