The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumor types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.
Antineoplastic Agents ; therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Molecular Targeted Therapy ; Neoplasms ; drug therapy ; genetics ; metabolism ; PTEN Phosphohydrolase ; genetics ; metabolism ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-ret ; metabolism ; Sirolimus ; therapeutic use ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism

INTRODUCTIONLymphaticovenular anastomosis (LVA) has been described as a treatment of chronic lymphoedema. This microsurgical technique is new and technically difficult. The small caliber and thin wall lymphatic vessels are difficult to identify and easily destroyed during the dissection.

MATERIALS AND METHODSWe describe a technique of performing lymphaticovenular anastomosis with patent blue dye enhancement. Our patient is a 50-year-old lady who suffers from chronic lymphoedema of the upper limb after mastectomy and axillary clearance for breast cancer 8 years ago.

RESULTSPatent blue dye is injected subdermally and is taken up readily by the draining lymphatic channels. This allows for easy identification of their course. The visualisation of the lumen of the lymphatic vessel facilitates microsurgical anastomosis. The patency of the anastomosis is also demonstrated by the dynamic pumping action of the lymphatic within the vessels.

CONCLUSIONPatent blue dye staining during lymphaticovenular anastomosis is a simple, effective and safe method for mapping suitable subdermal lymphatics, allowing for speedier dissection of the lymphatic vessels intraoperatively. This technique also helps in the confirmation of the success of the lymphaticovenular anastomosis.

Anastomosis, Surgical ; methods ; Coloring Agents ; Female ; Humans ; Lymphatic Metastasis ; Lymphatic Vessels ; Lymphedema ; etiology ; surgery ; Mastectomy ; adverse effects ; Microsurgery ; methods ; Middle Aged ; Rosaniline Dyes ; Sentinel Lymph Node Biopsy

INTRODUCTIONThis study aims to evaluate the outcome and safety of the deep inferior epigastric perforator (DIEP) flap for breast reconstruction in a group of Southeast Asian women treated in our unit and to identify risk factors for breast reconstruction using the DIEP flap in this population.

MATERIALS AND METHODSThis is a prospective study on 50 consecutive DIEP flap breast reconstructions by a single surgeon in an academic institution between July 1999 and July 2006. Data on patient demographics, diagnosis, procedure type, adjuvant and neoadjuvant treatments, risk factors and complications were prospectively collected and registered in a clinical database. Outcome variables include total flap loss, partial flap loss, fat necrosis and minor complications related to the donor site or flap. Known risk factors are analysed to determine if they affect outcome in terms of complication rate in this group of patients.

RESULTSTotal flap loss, partial flap loss and fat necrosis complication rates were 6%, 4% and 10%, respectively. Flap complication rates were comparable to those quoted by previous studies done worldwide. Obesity (BMI >27) is a statistically significant factor associated with development of DIEP flap complications in our population.

CONCLUSIONBreast reconstruction with DIEP flap is a safe and reliable method when used in Southeast Asian women, offering optimal results with less donor -site morbidity. Obesity increases the incidence of flap complication in this group of patients.

Abdomen ; surgery ; Adult ; Asian Continental Ancestry Group ; Breast ; surgery ; Databases, Factual ; Female ; Humans ; Mammaplasty ; adverse effects ; methods ; Microsurgery ; Middle Aged ; Multivariate Analysis ; Obesity ; Postoperative Complications ; Prospective Studies ; Rectus Abdominis ; surgery ; Risk Factors ; Surgical Flaps ; adverse effects ; Treatment Outcome ; Young Adult