Modern Japanese Approach to Pancreas Cancer

Abstract

Strong invasiveness, late appearance of clinical symptoms and a lack of efficient screening methods make the prognosis of pancreatic cancer dismal. Principal clues to early diagnosis of pancreatic cancer including pancreatic duct dilatation, diabetes, and intraductal papillary mucinous neoplasms are discussed, referring to many Japanese contributions. The Japan Pancreas Society (JPS) published Clinical Guidelines for Management of Pancreatic Cancer in 2006. The guidelines provide answers to 29 clinical questions with graded evidence-based recommendations. Diagnosis, chemotherapy, radiation therapy, surgical, and adjuvant treatments are addressed using two algorithms for the diagnosis and treatment. Treatment of the clinical stage IVa disease is still controversial, being resectable in some patients but not in others. Patients with no major arterial invasion should undergo resection rather than chemoradiation according to a prospective randomized study from Japan. The survival benefit of combined resection of the portal vein has not been proven yet. With regard to surgical treatments Japanese surgeons pursued cure by means of extended resection with complete dissection of retroperitoneal lymph nodes and neural plexus. However, several prospective randomized trials did not confirm the survival benefit of extended resection compared to standard resection with regional lymph node dissection only. One prospective randomized multi-institutional study from Japan yielded no significant difference in 1-year and 3-year survival rates after extended resection. The survival benefit of extended resection in those with lymph node metastasis demonstrated in one study may still justify D2 lymph node dissection. Current interest is focused on the significance of postoperative adjuvant chemotherapy. The analysis of the JPS Pancreatic Cancer Registry indicates that the 5-year survival rate of patients with resected pancreatic cancer has been significantly improved after the introduction of gemcitabine into Japan. A prospective randomized comparison of resection with and without postoperative administration of gemcitabine for 6 months conducted in Europe showed lengthened disease-free and overall 5-year survival rates. A Japanese group conducted a similar study with gemcitabine adjuvant treatment for 3 months after resection, which produced similarly prolonged disease free survival so far. If 5-year overall survival should not be improved, it may suggest the necessity of a longer period of adjuvant chemotherapy.