[in Japanese]

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Pancreatic cancer is associated with a poor prognosis and an overall 5-year survival rate of less than 5%. This is a serious issue that was left behind in the 21th century. Recently, an improvement in treatment is being achieved by progress in postoperative adjuvant chemotherapy. However, only 50% of cases receive adjuvant chemotherapy. To clarify the effectiveness of neoadjuvant chemotherapy, it is necessary to evaluate all patients of pancreatic cancer intending to undergo surgery by intention-to-treat analysis. It is possible that neoadjuvant chemotherapy may contribute an improvement in the prognosis as a whole for pancreatic cancer. We now have initiated a phase III randomized controlled trial to determine the efficacy of neoadjuvant chemotherapy with both gemcitabine and S-1. In the future, neoadjuvant therapy should be considered as a standard treatment for resectable pancreatic cancer.

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Adenocarcinoma of the pancreas carries a poor prognosis after curative resection, which offers the only chance for a cure. To improve such poor outcomes, several trials for post-operative adjuvant therapies have been carried out. Under the present situation in which the mainstay of treatment following resection is based primarily on gemcitabine, promising new therapeutic agents, and prognostic, as well as predictive biomarkers, are being reported. In this article, the history of post-operative therapies is reviewed and the future directions are discussed.

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For a long time, gemcitabine hydrochloride (GEM) had been used as standard care for unresectable pancreatic cancer. Subsequently, GEM plus erlotinib, and S-1 were added as other standard therapies in Japan, but there were no large differences in efficacy among these 3 regimens. FOLFIRINOX clearly showed superiority of survival over GEM by the randomized study that was conducted in France, and was rapidly added as a new option of standard care for the first line of unresectable pancreatic cancer. In Japan, a phase II study was conducted following the similar regimen, and since it showed favorable results, FOLFIRINOX was approved for treatment of unresectable pancreatic cancer in December 2013. FOLFIRINOX shows a good response rate, but it is composed of 4 drugs and has many adverse events. It should be used with intensive and prompt care to minimize side effects when compared with the other regimens. It is necessary for the physician to examine the eligibility of each individual case before practical use.

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Medical evidence-based Clinical Guidelines for Pancreatic Cancer have been revised in 2013 for the first time in 4 years since the previous version was published in 2009. In this revised set of guidelines, S-1 is recommended as adjuvant chemotherapy based on the results of the JASPAC-01 trial. Gemcitabine and erlotinib combination therapy and S-1 monotherapy are recommended as the regimen for patients with unresectable disease based on the results of the PA3 study and those of GEST study, respectively. The recommendations for unresectable disease have been revised in 2014, and FOLFIRINOX has been added to the therapeutic strategies recommended in the previous version. The development of more effective chemotherapeutic protocols is eagerly anticipated in the belief that they will improve the survival of patients with pancreatic cancer.

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A 67-year-old man with a pancreatic tumor was referred to our hospital on September 2013. The tumor was diagnosed as pancreatic tail cancer invading the splenic artery and vein with para-aortic lymph node metastasis (cStage IVb). After 4 courses of chemotherapy (S-1+gemcitabine), the size of the pancreatic tumor decreased from 21mm to 10mm on CT. Furthermore, CA19-9 level decreased from 67.4U/ml to 9.0U/ml and abnormal accumulation of FDG on FDG-PET in the pancreatic tumor and the para-aortic lymph node disappeared (the values of SUVmax before chemotherapy were 5.3 and 3.7, respectively). Re-evaluation after chemotherapy was cStage IVa pancreatic cancer without lymph node metastasis and curative resection was planned. Distal pancreatectomy with D2 lymph node dissection was performed. At the beginning of the surgery, sampling of the para-aortic lymph node was performed and frozen-section examination revealed no metastatic cancer cells. Histopathological examination of the resected specimens revealed no residual cancer cells in the pancreas and the 34 dissected lymph nodes including para-aortic node (pathological complete response).

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A 71-year-old woman was seen in a neighborhood hospital for upper abdominal pain. She was referred to our hospital because abdominal US revealed a 3cm cystic lesion in the body of the pancreas. Laboratory data showed elevated serum levels of DUPAN2 (170U/ml), abdominal enhanced CT showed a hypovascular 3cm cystic mass with partition in the pancreatic body. On MRI, the cystic wall showed low intensity in T2WI and DWI. EUS showed a 23mm mass including 14mm cyst and a solid component in the cyst. ERP showed the dilated distal main pancreatic duct and no communication between the pancreatic cyst and the main pancreatic duct. Under a preoperative diagnosis of neuroendocrine tumor or serous pseudopapillary tumor we perfomed a laparoscopic distal pancreatectomy. Pathological diagnosis showed autoimmune pancreatitis. In this report, we present the rare case of AIP involving a true cyst.

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The patient was a 54-year-old man who complained of right back pain. Radiographic examinations including computed tomography and magnetic resonance imaging revealed a pancreatic head tumor. An endoscopic ultrasound-guided fine-needle aspiration was performed and the histological diagnosis of solid-pseudopapillary neoplasm was confirmed. An enucleation of the tumor was done. Histologically, the tumor was composed of solid proliferation of tumor cells without capsule or pseudocyst formation. Tumor cells consisted of small round nuclei and light eosinophilic cytoplasm. Bizarre tumor cells with marked nuclear pleomorphism and nuclear atypia were also seen in a third area. Nuclear pleomorphism was suggested to be one of the histologic parameters associated with metastases, so careful follow-up should be needed.

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A 76-year-old woman who was followed after treatment of hepatocellular carcinoma was revealed of having dilatation of the main pancreatic duct of the body and tail of pancreas by computed tomography. Endoscopic ultrasonography (EUS) showed a low echoic region at the body of the pancreas and dilatation of the distal part of the main pancreatic duct. Endoscopic retrograde cholangio-pancreatography (ERCP) showed stenosis of the main pancreatic duct at the pancreatic body and dilatation of the upstream part of the main pancreatic duct. Cytological examination of the pancreatic juice revealed adenocarcinoma. Under the diagnosis of pancreatic body cancer, a distal pancreatectomy with splenectomy was performed. Pathological examination revealed carcinoma in situ in the main and branched pancreatic ducts. The distribution of carcinoma in situ did not completely correspond to the low echoic region demonstrated by EUS. Fibrotic change was detected in the pancreas parenchyma close to the carcinoma in situ and this region corresponded to the low echoic area disclosed by EUS. She is alive without any sign of recurrence two years and ten months after surgery.

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