Although upfront surgery has been the standard strategy for patients with resectable pancreatic cancer, the Prep-02/JSAP05 study has recently demonstrated that neoadjuvant chemotherapy significantly improves survival outcome of patients with planned pancreatic cancer resection. We conducted a single-center, retrospective analysis to confirm the effectiveness of neoadjuvant chemotherapy for 294 patients with pancreatic cancer who had planned resection. Neoadjuvant chemotherapy was administered generally with a regimen of 2 cycles of gemcitabine plus S1. The resection rate of the group treated with neoadjuvant chemotherapy, used in patients with more advanced disease than those treated with upfront surgery, was significantly higher than those treated with upfront surgery. No significant differences in perioperative findings between the groups was observed including operative time, blood loss, or initiation of post-operative adjuvant therapy. The median overall survival in the neoadjuvant chemotherapy group was 42.2 months, significantly longer than that of the upfront surgery group. Significant improvement of overall survival in patients who received neoadjuvant chemotherapy was also observed in the subset of resectable patients. This study confirms the superiority of neoadjuvant chemotherapy over upfront surgery as reported in the Prep-02/JSAP05 study. This strategy may be widely useful as a standard best practice for patients with resectable pancreatic cancer hereafter.

Enormous progress has been made in the development and standardization of adjuvant therapy regimens for patients with resected pancreatic ductal adenocarcinoma. Several randomized controlled trials clearly showed superiority of adjuvant chemotherapy over no chemotherapy. Adjuvant therapy with gemcitabine is considered indispensable since the results of the CONKO-001 trial. In Japan, JASPAC-01 showed that post-operative adjuvant chemotherapy with S-1 significantly extended overall survival compared with gemcitabine alone. In western countries, the ESPAC-4 trial showed significantly longer median overall survival after combination chemotherapy with gemcitabine plus capecitabine compared with gemcitabine monotherapy, and most recently, results from a multicenter French-Canadian randomized controlled trial showed considerably longer survival after adjuvant modified FOLFIRINOX compared with gemcitabine alone. These chemotherapy regimens are considered to be standard adjuvant therapy in western countries. The question remains as to whether these more aggressive regimens will be feasible in patients with reduced performance status, older age and more advanced disease. Accrual of the trials and follow-up data must be awaited.

Objectives: After the Prep-02/JSAP-05 trial demonstrated the efficacy of neoadjuvant chemotherapy using gemcitabine and S-1 (NAC-GS) for patients with resectable pancreatic cancer (RPC), the perioperative treatment for RPC changed significantly. The standard of care for patients with RPC was upfront surgery until now, but NAC-GS spread nationwide after the Prep-02/JSAP-05 trial. Concomitantly, it resulted in an increased need for histopathological diagnosis, leading to an increased use of endoscopic ultrasound guided fine needle aspiration (EUS-FNA).

Results: The accuracy and complication rate of EUS-FNA for RPC were 99% and 2.0% (2/100), respectively. The curative resection rate was high, similar to the Prep-02/JSAP-05 trial.

Conclusions: EUS-FNA is safe and effective. Since NAC-GS was introduced only recently, there is need for careful follow-up.

There has been a pressing need to develop the optimal regimen for neoadjuvant chemotherapy (NAC) for patients with pancreatic cancer (PC). Recently, surgical resection after neoadjuvant gemcitabine plus S-1 (GS) compared with upfront surgery in patients with resectable PC, showed significantly better overall survival in the Prep-02/JSAP05 study. We conducted a retrospective analysis of patients with resectable T3 PC who underwent neoadjuvant GS to evaluate the safety and effectiveness of neoadjuvant GS in a real-world setting. A total of 22 patients received neoadjuvant GS between July 2019 and June 2020. Major Grade 3-4 toxicities included neutropenia (55%), thrombocytopenia (9.1%), oral stomatitis (9.1%) and skin rash (4.5%). The reasons for treatment failure were unacceptable toxicities in 4 patients. The resection rate was 100% and R0 resection rate was 96%. Neoadjuvant GS in patients with resectable T3 PC may increase the chance for curative resection, but it is important to prevent and mange adverse events appropriately.

Up-front surgery followed by adjuvant chemotherapy was standard care for patients with resectable pancreatic cancer. Combination chemotherapy with gemcitabine plus S-1 (GS) as neoadjuvant treatment for patients with resectable pancreatic cancer significantly improved survival in the Prep-02/JSAP-05 trial. Following the results of the Prep-02/JSAP-05 trial, neoadjuvant GS therapy will be a standard option for the care of patients with resectable pancreatic cancer. Common adverse events of neoadjuvant GS therapy include neutropenia, febrile neutropenia and skin rash. These adverse events are manageable with adequate and prompt care. Multidisciplinary therapy with surgery, chemotherapy and radiotherapy might be required. It might be important to manage adverse events adequately to smoothly lead to the next therapy.

The efficacy of neoadjuvant chemotherapy (NAC) has been reported and the importance of preoperative biliary drainage for safe administration of NAC has been shown. Recently, self-expandable metallic stents (SEMS) tend to be chosen because of longer stent patency, but there are many problems that are still unresolved. Preoperative biliary drainage should be performed in conjunction with a surgical consultation at the same institution. We reviewed the current status of preoperative biliary drainage in patients with pancreatic cancer in Japan.

Pathologic assessment of the effects of treatment may provide important information about residual cancer cells, such as the presence of necrotic or viable cancer cells. It is expected that pathologic assessment of treatment effects is useful to predict patient outcomes, as well as to decide the treatment plan. We will show characteristic pathologic changes after neoadjuvant therapy and discuss three common pathologic evaluation systems.

The Prep-02/JSAP-05 study showed that preoperative gemcitabine with S-1 (GS) significantly prolongs overall survival. Based on this result, the standard treatment sequence for resectable pancreatic ductal adenocarcinoma is preoperative chemotherapy, appropriate radical resection, and postoperative adjuvant chemotherapy. Patients with positive peritoneal washing cytology had a significantly poorer overall survival after surgery. Peritoneal washing cytology may play an important role in determining resectability. Staging laparoscopy is used to detect peritoneal dissemination and small liver metastases as well as to obtain peritoneal washings for cytologic analysis. While staging laparoscopy contributes to determining resectability, the indications are controversial because of possible complications. Extended lymph node and nerve plexus dissection should not be performed because they do not improve the postoperative prognosis and may make continued administration of adjuvant chemotherapy difficult. Patients' prognosis may be improved by carrying out a series of procedures from diagnosis to treatment without delay.

Anatomical tumor extension as well as the biological behavior of pancreatic cancer (PC) are emphasized for designing an appropriate treatment strategy in patients with PC. In this context, a highly elevated CA19-9 level was incorporated with borderline resectability as one of the biological factors, and even in anatomically resectable cases, patients with a very elevated CA19-9 level are classified as borderline resectable (biological borderline: biological BR). The appropriate assessment of the biological BR factor is important to optimize the treatment strategy in each individual patient with PC. In neoadjuvant chemoradiation therapy (CRT) for resectable (R) and BR pancreatic cancer, oncologic outcomes of biological BRPC (BR-biol) were significantly unfavorable compared with those with resectable PC and comparable with those of anatomical BRPC (BR-anat). Outcomes of BR-biol cases with normalization of serum CA19-9 levels (<37U/ml) after neoadjuvant CRT (post-CA19-9) (nBR-biol) were significantly favorable compared with those of BR-biol with a failure to normalize post-CA19-9 (eBR-biol) and comparable with those with resectable disease with normalized post-CA19-9. These observations suggest that post-CA19-9 normalization indicates biological downstaging in biological BRPC in the neoadjuvant CRT strategy for patients with PC.

GEM+nab-paclitaxel (GNP) has a significantly positive impact on the treatment of pancreatic cancers. In this report, we describe short- and long-term outcomes of a multidisciplinary approach for borderline resectable cancers using GNP as neoadjuvant therapy (NAT group, N = 47) compared with conventional surgery-upfront treatment (SU group, N = 76). Intention-to-treat analysis of the entire cohort revealed that the NAT group had a significantly longer overall survival (median survival time; 31.5 vs. 18.1months, P = 0.047) and progression free survival (16.8 vs. 9.0 months, P = 0.008). Among patients who underwent resection (N = 98), operation duration, blood loss, and severity of postoperative complications were similar among the groups. The R0 resection rate (0mm rule) for the NAT group was significantly higher than that of the SU group (89 vs. 64%, P = 0.0051). A multidisciplinary approach using GNP is a feasible and promising treatment option for patients with borderline resectable pancreatic cancers.

Surgical resection is only the potential cure for patients with pancreatic cancer and is also associated with serious complications. In recent years, the use of novel chemotherapy and radiotherapy approaches has improved survival in patients with locally advanced pancreatic cancer. Evidence regarding the efficacy of extended pancreatectomy has become more important. Vein resection is justified with limited indications. Arterial resection has not been shown to be beneficial, and distal pancreatectomy with celiac axis resection may be useful in certain (neo) adjuvant settings. The benefit of extended lymphadenectomy has not been shown, and benefits of standard lymphadenectomy remain unclear. The prognosis of patients with para-aortic lymph node metastases needs further evaluation.

Educational programs have been implemented in several hospitals in Japan to provide information regarding treatment, management of side effects, and management of daily life while undergoing treatment to patients with pancreaticobiliary cancer and their caregivers. However, the impact of such educational programs on patients and caregivers has not yet been fully clarified. We conducted a prospective assessment of the changes in the levels of knowledge and distress associated with the information provided during such an educational program at our institution using a self-administered questionnaire and Distress Thermometer in 33 patients with advanced pancreaticobiliary cancer and 50 caregivers. The scores for items pertaining to knowledge about the disease increased significantly and the scores for distress pertaining to the disease decreased significantly for both patients and caregivers. These findings suggest that education may improve the level of knowledge of the disease and decrease the distress level associated with the diagnosis in patients with pancreaticobiliary cancer and their caregivers, although we believe that careful monitoring of the participants is necessary, because these findings reveal that the distress level increased in some patients.

A 65-year-old man was admitted with upper abdominal fullness. Esophagogastroduodenoscopy and upper gastrointestinal radiography showed duodenal stenosis extending from the bulb to the superior duodenal angulus. Contrast-enhanced abdominal computed tomography scan revealed a tumor with delayed enhancement of a thickened duodenal bulb, and histopathological examination of a biopsy specimen showed adenocarcinoma. Based on these findings, we suspected duodenal cancer and performed a subtotal pylorus-preserving pancreaticoduodenectomy. We found an elastic white duodenal mass measuring approximately 3cm in size on macroscopic examination. Histopathological examination of the resected specimen showed a moderately differentiated adenocarcinoma with islets of Langerhans in the submucosal layer and the muscularis propria. Immunohistochemical examination confirmed the diagnosis of adenocarcinoma originating from duodenal heterotopic pancreatic tissue. We report a rare adenocarcinoma originating in duodenal heterotopic pancreatic tissue.

A 64-year-old woman presented with acute abdominal pain. Severe acute pancreatitis was diagnosed by serum chemistry studies and enhanced abdominal computed tomography (CT) scan, and she was admitted. Enhanced abdominal CT scan and abdominal magnetic resonance imaging revealed a 20mm hypervascular tumor containing a cyst in the uncinate process of the pancreas. Endoscopic ultrasound-fine needle aspiration led to the diagnosis of a pancreatic neuroendocrine tumor, and subtotal stomach-preserving pancreatoduodenectomy was performed. Acute pancreatitis is a rare complication of a pancreatic neuroendocrine tumor. However, for patients where a tumor is located near the main pancreatic duct, care must be taken since such patients may develop acute pancreatitis and have a complicated clinical course.

We present a patient with a metachronous metastasis of a mesenchymal chondrosarcoma to the pancreas 11 years after primary tumor resection. The patient was a 40 year old male with a history of diabetes mellitus and hypertension. He was diagnosed with a mesenchymal chondrosarcoma at age 29 and underwent wide resection of the primary lesion with intraoperative radiation therapy after neoadjuvant chemotherapy. Postoperatively, he received adjuvant chemotherapy. He underwent metastasectomy at age 31 for a pulmonary metastasis and at age 33 for a cerebral metastasis and abdominal subcutaneous metastasis. Seven years later, there was significant elevation of serum glucose to 527mg/dl and CT scan, MRI and PET/CT scan revealed a pancreatic metastasis. Subtotal stomach-preserving pancreaticoduodenectomy was performed. At present, he is alive 6 months after operation and with intensive follow up.

We investigated reports of tumors metastatic to the pancreas from bone and soft tissue and found 13 cases including the present patient. In case of a synchronous metastasis, the patients survive a relatively short time. Patients who underwent metastasectomy generally survive for nearly 10 years. If a solitary metastasis is found from bone or soft tissue tumors, metastasectomy may be appropriate.