Can we predict pathologic complete response before surgery for locally advanced rectal cancer treated with preoperative chemoradiation therapy?

Background

Pathologic complete response has been proven to have oncological benefits for locally advanced rectal cancer treated with chemoradiation therapy. The aims of this study are to analyze and determine the factors to predict pathologic complete response for patients treated with preoperative neoadjuvant therapy.

Methods

Patients with biopsy-proven, locally advanced rectal cancer were treated neoadjuvantly followed by radical surgical resection. Tumors were re-assessed after completing chemoradiation, including pelvic magnetic resonance images, colonoscopic examination, and re-biopsy. The results of examination were compared with the final pathologic status.

Results

A retrospective chart review of 166 patients was conducted. Twenty-five patients (15.1%) had pathologic complete response after chemoradiation. The 5-year overall survival rates were better in the complete response group than the residual tumor group (91.1% vs. 70.8%; P?=?0.047), and there were also significant differences in the 5-year disease-free survival rates between these two groups (91.1% vs. 70.2%; P?=?0.027). The prediction rates for pathologic complete response by re-biopsy, magnetic resonance images, and colonoscopy were 21.4%, 33.3%, and 53.8%, respectively. In addition, when we further combine the results of colonoscopic findings and re-biopsy, the prediction rate for pathologic complete response reached 77.8% (P?=?0.009).

Conclusions

Combining the results of the re-biopsy and post-treatment colonoscopic findings, we can achieve a good prediction rate for pathologic complete response. Post-treatment magnetic resonance images are not useful tools in predicting tumor clearance following chemoradiation.     

Use of antibiotic prophylaxis in elective inguinal hernia repair in adults in London and south-east England: a cross-sectional survey

Purpose

Evidence regarding whether or not antibiotic prophylaxis is beneficial in preventing post-operative surgical site infection in adult inguinal hernia repair is conflicting. A recent Cochrane review based on 17 randomised trials did not reach a conclusion on this subject. This study aimed to describe the current practice and determine whether clinical equipoise is prevalent.

Methods

Surgeons in training were recruited to administer the Survey of Hernia Antibiotic Prophylaxis usE survey to consultant-level general surgeons in London and the south-east of England on their practices and beliefs regarding antibiotic prophylaxis in adult elective inguinal hernia repair. Local prophylaxis guidelines for the participating hospital sites were also determined.

Results

The study was conducted at 34 different sites and received completed surveys from 229 out of a possible 245 surgeons, a 93 % response rate. Overall, a large majority of hospital guidelines (22/28) and surgeons’ personal beliefs (192/229, 84 %) supported the use of single-dose pre-operative intravenous antibiotic prophylaxis in inguinal hernia repair, although there was considerable variation in the regimens in use. The most widely used regimen was intravenous co-amoxiclav (1.2 g). Less than half of surgeons were adherent to their own hospital antibiotic guidelines for this procedure, although many incorrectly believed that they were following these.

Conclusion

In the south-east of England, there is a strong majority of surgical opinion in favour of the use of antibiotic prophylaxis in this procedure. It is therefore likely to be extremely difficult to conduct further randomised studies in the UK to support or refute the effectiveness of prophylaxis in this commonly performed procedure.     

An enzymatic approach to configurationally rare trans‐androsteronyl‐α‐glucoside and Its potential anticancer application

Enzymatic glycosylation of sterols/steroids with glycosyltransferase HP0421 shows protein plasticity on generation of configurationally rare steryl‐α‐glucosides. Investigation of trans‐androsteronyl‐α‐glucoside on tamoxifen‐treated MCF‐7 breast cancer cells shows dose‐dependent depression of cell viability and enhanced drug effectiveness, illustrating a new avenue for the production of novel steryl‐α‐glucosides with useful biological activities.     

Microfluidic one-step synthesis of Fe3O4-chitosan composite particles and their applications

This paper demonstrates a simple and easy approach for the one-step synthesis of Fe₃O₄-chitosan composite particles with tadpole-like shape. The length and diameter of the particles were adjustable from 638.3 μm to ca. 798 μm (length), and from 290 μm to 412 μm (diameter) by varying the flow rate of the dispersed phase. Mitoxantrone was used as the model drug in the drug release study. The encapsulation rate of the drug was 71% for chitosan particles, and 69% for magnetic iron oxide-chitosan particles, respectively. The iron oxide-chitosan composite particles had a faster release rate (up to 41.6% at the third hour) than the chitosan particles (about 24.6%). These iron oxide-chitosan composite particles are potentially useful for biomedical applications, such as magnetic responsive drug carriers, magnetic resonance imaging (MRI) enhancers, in the future.     

Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus

We sought to determine whether intramuscular injection of a recombinant adeno-associated virus (rAAV) vector expressing human factor IX (hF.IX) could direct expression of therapeutic levels of the transgene in experimental animals. High titer (10¹²–10¹³ vector genomes/ml) rAAV expressing hF.IX was prepared, purified, and injected into hindlimb muscles of C57BL/6 mice and Rag 1 mice. In the immunocompetent C57BL/6 mice, immunofluorescence staining of muscle harvested 3 months after injection demonstrated the presence of hF.IX protein, and PCR analysis of muscle DNA was positive for AAV DNA, but no hF.IX was detected in mouse plasma. Further studies showed that these mice had developed circulating antibodies to hF.IX. In follow-up experiments in Rag 1 mice, which carry a mutation in the recombinase activating gene-1 and thus lack functional B and T cells, similar results were seen on DNA analysis of muscle, but these mice also demonstrated therapeutic levels (200–350 ng/ml) of F.IX in the plasma. The time course of F.IX expression demonstrates that levels gradually increase over a period of several weeks before reaching a plateau that is stable 6 months after injection. In other experiments we demonstrate colocalization of hF.IX and collagen IV in intersitial spaces between muscle fibers. Collagen IV has recently been identified as a F.IX-binding protein; this finding explains the unusual pattern of immunofluorescent staining for F.IX shown in these experiments. Thus rAAV can be used to direct stable expression of therapeutic levels of F.IX after intramuscular injection and is a feasible strategy for treatment of patients with hemophilia B.