Long-term outcomes by a transanal approach to total mesorectal excision for rectal cancer.

BACKGROUND: The challenge of performing a good total mesorectal excision (TME) dissection, particularly in the distal 1/3 of the rectum, has spurred interest in new techniques. Robotic surgery is advocated by some, and more recently, a "new" approach, the transanal total mesorectal excision, has been popularized to address this problem. While great interest in this technique exists, little long-term outcome data are available. We have been utilizing a transanal abdominal transanal approach to TME in order to facilitate the distal dissection, and here, we provide our long-term outcomes using this approach in the management of rectal cancer. METHODS: From a prospectively maintained rectal cancer database, we identified 373 consecutive rectal cancers treated with sphincter preservation surgery through a combined transanal and abdominal approach to TME. Perioperative, pathological, and oncologic outcomes were analyzed. RESULTS: Three hundred and seventy-three patients with rectal cancer underwent a transanally initiated TME with mean follow-up of 5.5 years. 91% of cancers were in the distal rectum. 68.9% were men and 53.2% of cancers were tethered or fixed on presentation. 97.7% received neoadjuvant radiotherapy (mean 5405 cGy, 5-fluorouracil based); average time from completion of neoadjuvant therapy to surgery was 11 weeks. 180 and 193 patients underwent completion of their operation through open and laparoscopic abdominal approaches. 96% of TME specimens were complete/near complete, 94% had a negative circumferential resection margin, and 98.6% had a negative distal margin. Perioperative morbidity and mortality rates were 13.4 and 0.3%. Overall local recurrence (LR), DM, and Kaplan-Meier 5-year actuarial survival were 7.4, 19.5, and 90%, respectively. CONCLUSION: This is the first report of long-term data using a transanal approach to TME supporting this approach for rectal cancer. Our data with 5-year follow-up show that adequate distal and circumferential margins with very good-quality TME specimens, and a low risk for LR with excellent overall survival can be achieved using this technique. Our long-term results support the promising reports of early experiences in the literature.

Preliminary evaluation of a predictive blood assay to identify patients at high risk of chemotherapy-induced nausea.

PURPOSE: The aim of this study was to test a new blood-based assay for its ability to predict delayed chemotherapy-induced nausea. METHODS: Blood drawn from consented patients prior to receiving their first platinum-based therapy was tested for glutathione recycling capacity and normalized to total red cell numbers. This number was used to predict nausea and then compared to patient reported outcomes using the Rotterdam Symptom Check List and medical records. RESULTS: We show that the pathways involved in the glutathione recycling are stable for at least 48 h and that the test was able to correctly classify the risk of nausea for 89.1 % of the patients. The overall incidence of nausea was 21.9 % while women had an incidence of 29.6 %. CONCLUSIONS: This might be the first objective test to predict delayed nausea for cancer patients receiving highly emetogenic chemotherapy. We believe that this assay could better guide clinicians in their efforts to provide optimal patient-oriented care.

Targeting the proteasome as a therapeutic strategy against haematological malignancies.

The ubiquitin-proteasome pathway is responsible for the vast majority of regulated eukaryotic intracellular proteolysis. Inhibition of the proteasome induces beneficial antitumour effects by blocking cell-cycle progression, inducing apoptosis and suppressing angiogenesis. Bortezomib is the first proteasome inhibitor to reach the clinical arena, where Phase I - III trials verified its activity against relapsed/refractory multiple myeloma. Testing is ongoing to determine bortezomib's role in front-line therapy of this plasma cell dyscrasia, as well as in non-Hodgkin's lymphoma, in which encouraging single-agent activity has been seen. Proteasome inhibition is also a rational strategy to overcome chemoresistance and induce chemosensitisation. Combinations of bortezomib and other agents have enhanced efficacy, and additional studies are probing the activity of several regimens in lymphoid and myeloid malignancies. The current state of knowledge about the activity of bortezomib, both alone and in combination with standard chemotherapeutics, as part of the emerging armamentarium against haematological malignancies is reviewed.