Survival after surgical management of pancreatic adenocarcinoma: does curative and radical surgery truly exist?

Abstract

Surgery for pancreatic cancer offers a low success rate but it provides the only likelihood of cure. Modern series show that, in experienced hands, the standard Whipple procedure is associated with a 5-year survival of 10%-20%, with a perioperative mortality rate of less than 5%. Most patients, however, will develop recurrent disease within 2 years after curative treatment. This occurs, usually, either at the site of resection or in the liver. This suggests the presence of micrometastases at the time of operation. Negative lymph nodes are the strongest predictor for long-term survival. Other predictors for a favourable outcome are tumour size, radical surgery and a histopathologically well-differentiated tumour. Adjuvant therapy has, so far, shown only modest results, with 5FU chemotherapy, to date, the only proven agent able to increase survival. Nowadays, the choice of therapy should be based on histopathological assessment of the tumour. Knowledge of the molecular basis of pancreatic cancer has led to various discoveries concerning its character and type. Well-known examples of genetic mutations in adenocarcinoma of the pancreas are k-ras, p53, p16, DPC4. Use of molecular diagnostics and markers in the assessment of tumour biology may, in future, reveal important subtypes of this type of tumour and may possibly predict the response to adjuvant therapy. Defining the subtypes of pancreatic cancer will, hopefully, lead to target-specific, less toxic and finally more effective therapies. Long-term survival is observed in only a very small group of patients, contradicting the published actuarial survival rates of 10%-45%. Assessment of clinical benefit from surgery and adjuvant therapy should, therefore, not only be based on actuarial survival but also on progression-free survival, actual survival, median survival and quality of life (QOL) indicators. Survival in surgical series is usually calculated by actuarial methods. If there is no information on the total number of patients and the number of actual survivors, and no clear definition of the subset of patients, actuarial survival curves can prove to be misleading. Proper assessment of QOL after surgery and adjuvant therapy is of the utmost importance, as improvements in survival rates have, so far, proved to be disappointing.

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

“…In addition, these tumors are usually resistant to chemotherapy and radiation. 22,23 Therefore, a new therapeutic strategy is required to improve the prognosis. We previously showed that Bone Morphogenetic Protein 4 (BMP4) induced EMT in pancreatic cancer cells with up-regulation of MSX2, and inactivation of MSX2 by siRNA suppressed EMT and inhibited the growth and metastasis of pancreatic cancer in vivo, suggesting that blockade of EMT could suppress tumor development.…”

RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy

“…[2][3][4] Even so, the 5 y survival rate among those radically operated patients is only about 5-20%. 2,5,6 To date, chemotherapy still remains the most important adjuvant therapy in patients with pancreatic malignancies. Currently, gemcitabine has been recommended as the first-line therapy for advanced pancreatic cancer.…”

Tranilast strongly sensitizes pancreatic cancer cells to gemcitabine via decreasing protein expression of ribonucleotide reductase 1

“…KP4 was seeded in 96-well culture plates each 1x10 4 cell/ well and incubated at 37˚C in a humidified atmosphere overnight. Then the cells were exposed to tranilast for 48 h, at a concentration ranging from 0 to 400 μM.…”

“…Effect of RRM1 siRNA on sensitivity to Gem or CDDP was analyzed as follows: 1x10 4 of KP4 cells were seeded onto 6-well plates. dsRNA for RRM1 was transfected in duplicate at a final concentration of 1 or 10 nM.…”