Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.

PURPOSE: Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. PATIENTS AND METHODS: During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). RESULTS: Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. CONCLUSION: These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.     

Development of the Proteasome Inhibitor Velcade™ (Bortezomib)

The dipeptide boronic acid analogue VELCADE™ (Bortezomib; formerly known as PS-341, LDP-341 and MLM341) is a potent and selective inhibitor of the proteasome, a multicatalytic enzyme that mediates many cellular regulatory signals by degrading regulatory proteins or their inhibitors. The proteasome is, thus, a potential target for pharmacological agents. Bortezomib, the first proteasome inhibitor to reach clinical trials, has shown in vitro and in vivo activity against a variety of malignancies, including myeloma, chronic lymphocytic leukemia, prostate cancer, pancreatic cancer, and colon cancer. The drug is rapidly cleared from the vascular compartment, but a novel pharmacodynamic assay has shown that bortezomib-mediated proteasome blockade is dose-dependent and reversible. Based on phase I studies demonstrating that bortezomib has manageable toxicities in patients with advanced cancers, phase II trials have been initiated for both solid and hematological malignancies.     

Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces

The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded ‘amoeboid-like’ mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar ‘mesenchymal-like’ mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.     

Colorectal endoscopic submucosal dissection: Systematic review of mid‐term clinical outcomes

With a drive towards minimally invasive surgery, endoscopic submucosal dissection (ESD) is now gaining popularity. In a number of East Asian countries, ESD is now the treatment of choice for early non‐metastatic gastric cancer, but the outcomes of ESD for colorectal lesions are unclear. The present review summarizes the mid‐term outcomes of colorectal ESD including complication and recurrence rates. A systematic literature search was done in May 2014, identifying 20 publications reporting the outcomes of colorectal ESD which were included in this review. En‐bloc resection rates, complete (R0) resection rates, endoscopic clearance rates, complication and recurrences rates were analyzed. Statistical pooling was done to calculate weighted means using random effects modeling. Twenty studies reporting the outcomes of 3060 colorectal ESD procedures were reported. Overall weighted en‐bloc resection rate was 89% (95% CI: 83–94%), R0 resection rate 76% (95% CI: 69–83%), endoscopic clearance rate 94% (95% CI: 90–97%) and recurrence rate 1% (95% CI: 0.5–2%). Studies that followed up patients for over 1 year were found to have an en‐bloc resection rate of 91% (95% CI: 86–96%), R0 resection rate of 81% (95% CI: 75–88%), endoscopic clearance rate 93% (95% CI: 90–97%) and recurrence rate of 0.8% (95% CI: 0.4–1%). Colorectal ESD can be carried out effectively and safely with a 1% recurrence rate. Further studies with longer follow‐up periods are required to determine whether colorectal ESD is a viable alternative to conventional surgical therapy.     

A comparison of 2 methods of vaginal cuff closure during robotic hysterectomy

ObjectiveTo compare 2 methods of vaginal cuff closure with regard to safety, ease of use, and postoperative outcome.MethodsAll patients undergoing robotic-assisted total hysterectomy by a gynecologic oncologist from July 1, 2010, to July 1, 2011, at Northwestern Memorial Prentice Women's Hospital were included in a retrospective analysis. Providers used either 2–0 monofilament synthetic absorbable suture to close the vaginal cuff in a running fashion, secured with an absorbable suture clip at the angles and then knotted in the middle, or 2–0 absorbable unidirectional barbed suture with a welded-loop closure in a running fashion.ResultsA total of 134 patients underwent robotic-assisted total hysterectomy. The 2–0 tied monofilament closure was used in 58 patients, and the 2–0 barbed knotless closure was used in 76 patients. There were no instances of vaginal cuff dehiscence or vaginal cuff cellulitis. Rates of vaginal spotting and bleeding were comparable between the groups (12.0% spotting in the monofilament suture group vs 13.0% spotting in the barbed suture group). All vaginal cuff bleeding resolved on its own without significant intervention.ConclusionThe use of either a 2–0 welded-loop unidirectional barbed suture or a 2–0 monofilament absorbable suture to close the vaginal cuff is safe and well tolerated.