Radical Resection Surgery Research Articles

Combining Imatinib with Surgery in Gastrointestinal Stromal Tumors: Rationale and Ongoing Trials

Gastrointestinal stromal tumor (GIST) has become a well-recognized pathologic entity defined by expression of the KIT protein and often associated with gain of function mutations of the c-KIT oncogene. Imatinib, a specific inhibitor of the aberrant KIT protein, is an approved, well-tolerated oral drug for the management of metastatic or inoperable GIST. Traditional radical surgery resection for locally advanced, recurrent, or metastatic GIST is associated with a poor outcome. The rationale for combining imatinib with surgery for GIST, either as an adjuvant agent in the situation of primary resection for patients at high risk or in the neoadjuvant setting for patients with locally advanced, recurrent, or metastatic disease, is compelling in the continuous effort to improve disease-free and overall survival. Several clinical trials are addressing these issues as well as timing of surgery, assessment of drug response, and the addition of surgical resection in the situation of focal progressive disease on imatinib. The results of these studies will be meaningful in future standard therapy consideration.

Photodynamic therapy in gastrointestinal cancer: a realistic option?

Photodynamic therapy is now a useful and practical option of the local treatment of gastrointestinal cancers. There is increasing screening and surveillance of patients at risk of oesophageal and gastric cancers. The early detection of disease is often unhelpful if an elderly or frail patient needs to be subjected to radical resectional surgery. Photodynamic therapy can eradicate and cure early mucosal disease following a single endoscopic treatment. If the disease is more advanced good local control and palliation is often possible. Overall, palliation can often be achieved using simpler methods which are highly effective and not associated with the problems of prolonged photosensitisation. It is rapidly becoming clear that the ideal indication is for the treatment of dysplastic lesions in the oesophagus associated with columnar-lined oesophagus (Barrett's oesophagus). In these circumstances a heterogeneous field change often with multifocal dysplasia or cancer can be widely eradicated. Similar areas of squamous dysplasia in the upper oesophagus can be treated. At present a major complication of stricture formation is associated with the use of some photosensitisers. The treatment of cancer at the ampulla of Vater and choriocarcinoma is also proving very effective. The treatment can be performed at endoscopy and is well tolerated and safe.

Application of green fluorescent protein technology in the study of membrane-trafficking in living neurons

Whole body optical imaging using bioluminescence or fluorescence is one of the most rapidly emerging technologies to non-invasively follow all kinds of molecular and cellular processes in small animals. Using tomographic approaches it is now also possible to get better quantitative data. Due to its sensitivity and simplicity it is now also widely used in drug development and drug screening. Finally, using near infrared fluorescent probes that have much deeper penetration also opens up new exciting applications such as intra-operative image guided surgery for sentinel lymph node mapping and radical resection of tumours.Recent advances in imaging strategies that reveal cellular and molecular biological events in real-time facilitate our understanding of biological processes occurring in living animals. The development of molecular tags, such as green fluorescent protein (GFP) from the jellyfish Aequorea victoria, red fluorescent proteins (RFP) from the Discosoma species (dsRed2) and luciferase (Luc) from the firefly Photinus pyralis (fLuc) and the sea pansy Renilla (rLuc), has revolutionised research over the past decade, allowing complex biochemical processes to be associated with the functioning of proteins in living cells.Optical technologies, both microscopic and macroscopic, are developing fast. Recent technical advances for imaging weak visible light sources using cooled charged coupled device (CCCD) cameras, peltier cooled detectors and micro-plate channel intensifiers allow detection of photon emission from inside the tissues of small animals. Whole body fluorescent imaging (FLI) and bioluminescent imaging (BLI) are now applied to study cell- and tissue-specific gene promoter activity and also to follow trafficking, differentiation and fate of i.e. GFP or RFP and/or luciferase expressing cells, or biological processes like apoptosis, protein–protein interaction, angiogenesis, proteolysis and gene-transfer. Optical imaging (OI) and optical reporter systems are also very cost-effective and time-efficient and they are particularly well suited for small animal imaging and for in vitro assays to validate different reporter systems.

Role of radiation in the management of adult patients with sarcoma of soft tissue.

Radiation in moderate dose levels, viz. 60-65 Gy at 2 Gy/fraction, administered in combination with conservative surgery, yields local control frequencies at least comparable to those achieved by radical resectional surgery alone. The clinical interest in this management strategy is the reduction in the scope of the resection and a consequent gain in cosmetic and functional status. This combined approach is favored for sarcomas so situated that resection with wide margin, > or = 2 cm at the most narrow, cannot be realized unless there is a clinically important loss in function. Where radical surgery is planned, there must be great care in assessment of the probability of achieving good margins. The patient is ill served if there is radical surgery and then, because of close margins, postoperative radiation is required. There appears to be clinical gain for the patient with a large sarcoma by administering the radiation preoperatively. Advantages include smaller treatment volume and higher local control rates. The management of the surgical wound in the irradiated patient is discussed. Also, brief consideration is given to current use of brachytherapy, high linear energy transfer (LET) radiation, and combination of radiation and chemotherapy.