Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of gastrointestinal cancer, with a 5-year survival rate of 5%; it remains a significant, unresolved therapeutic challenge. Its aggressive features include insidious presentation, unresectability due to early involvement of major vessels, debilitating symptoms at the late stage and de novo chemoresistance. However, according to the Japan Pancreatic Cancer Registry, the 5-year survival of UICC Stages 0 and 1a are 85.8% and 68.7%, respectively. Early diagnosis plays an important role in improving the overall survival of patients with PDAC; therefore, efforts should focus on early diagnosis and the reliable identification of patients who will most likely benefit from major surgical intervention. Patients with risk factors, including family history, accompanying disease, diabetes mellitus, chronic pancreatitis and intraductal papillary mucinous neoplasms (IPMN), should be followed up for early detection of PDAC. In Japan, a national team has undertaken such surveillance of patients with IPMN. The protocol comprises a semi-annual follow up using various modalities to detect not only IPMN carcinoma, but also PDAC concomitant with IPMN. I will address this protocol in detail. The most accurate imaging technique for PDAC diagnosis and staging is considered to be contrast-enhanced computed tomography (CECT). Whereas CT should be the first choice in patients with suspected PDAC, endoscopic ultrasound (EUS) is the most accurate, particularly for detecting small lesions (< 10 mm). EUS combines the potential of endoscopy, which enables visualization of the mucosal surface of the gastrointestinal (GI) tract, with ultrasonography. Thus, EUS is able to provide detailed, high-resolution images of the pancreas. However, whether a lesion is malignant or benign is unable to be discriminated solely from EUS imaging features. Obtaining samples from suspicious lesions or lymph nodes using EUS-guided fine-needle aspiration (FNA), offers the potential for cytological or histological diagnoses of pancreatic lesions with high sensitivity and specificity. Since accurate preoperative evaluation is essential to select the appropriate management strategy, the roles of EUS and EUS-FNA are crucial. Stage 0 PDAC (carcinoma in situ) has recently been discovered. This stage of PDAC is unable to be diagnosed using EUS-FNA, because EUS-FNA is only applicable after PDAC forms a cancerous mass (worse than stage1). Thus, diagnostic methods other than imaging require development. Presently, endoscopic retrograde pancreatography (ERP) combined with cytology is able to detect Stage 0 PDAC, and in Japan, nasopancreatic drainage tubes have recently been used to collect pancreatic juice for cytodiagnosis. I would also like to introduce this method.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of gastrointestinalcancer, with a 5-year survival rate of 5%; it remains a significant, unresolvedtherapeutic challenge. Its aggressive features include insidious presentation,unresectability due to early involvement of major vessels, debilitating symptomsat the late stage and de novo chemoresistance.However, according to the Japan Pancreatic Cancer Registry, the 5-year survivalof UICC Stages 0 and 1a are 85.8% and 68.7%, respectively.Early diagnosis plays an important role in improving the overall survival ofpatients with PDAC; therefore, efforts should focus on early diagnosis and thereliable identification of patients who will most likely benefit from major surgicalintervention.Patients with risk factors, including family history, accompanying disease,diabetes mellitus, chronic pancreatitis and intraductal papillary mucinousneoplasms (IPMN), should be followed up for early detection of PDAC. In Japan,a national team has undertaken such surveillance of patients with IPMN. Theprotocol comprises a semi-annual follow up using various modalities to detectnot only IPMN carcinoma, but also PDAC concomitant with IPMN. I will addressthis protocol in detail.The most accurate imaging technique for PDAC diagnosis and staging isconsidered to be contrast-enhanced computed tomography (CECT). WhereasCT should be the first choice in patients with suspected PDAC, endoscopicultrasound (EUS) is the most accurate, particularly for detecting small lesions (<10 mm). EUS combines the potential of endoscopy, which enables visualizationof the mucosal surface of the gastrointestinal (GI) tract, with ultrasonography.Thus, EUS is able to provide detailed, high-resolution images of the pancreas.However, whether a lesion is malignant or benign is unable to be discriminatedsolely from EUS imaging features. Obtaining samples from suspicious lesions orlymph nodes using EUS-guided fine-needle aspiration (FNA), offers the potentialfor cytological or histological diagnoses of pancreatic lesions with high sensitivityand specificity. Since accurate preoperative evaluation is essential to select theappropriate management strategy, the roles of EUS and EUS-FNA are crucial.Stage 0 PDAC (carcinoma in situ) has recently been discovered. This stage of PDACis unable to be diagnosed using EUS-FNA, because EUS-FNA is only applicableafter PDAC forms a cancerous mass (worse than stage1). Thus, diagnostic methodsother than imaging require development. Presently, endoscopic retrogradepancreatography (ERP) combined with cytology is able to detect Stage 0 PDAC,and in Japan, nasopancreatic drainage tubes have recently been used to collectpancreatic juice for cytodiagnosis. I would also like to introduce this method.

Background/Aims: High-grade pancreatic intraepithelial neoplasia and invasive pancreatic duc-tal adenocarcinoma ≤10 mm are targets for early detection of pancreatic cancer. However, their imaging characteristics are unknown. We aimed to identify endoscopic ultrasound findings for the detection of these lesions. Methods: Patients diagnosed with high-grade pancreatic intraepithelial neoplasia (n=29), pan-creatic ductal adenocarcinoma ≤10 mm (n=11) (who underwent surgical resection), or benignmain pancreatic duct stenosis (n=20) between January 2014 and January 2021 were retrospectively included. Six features differentiating these lesions were examined by endoscopic ultraso-nography: main pancreatic duct stenosis, upstream main pancreatic duct dilation, hypoechoic areas surrounding the main pancreatic duct irregularities (mottled areas without demarcation or round areas with demarcation), branch duct dilation, prominent lobular segmentation, and atrophy. Interobserver agreement was assessed by two independent observers. Results: Hypoechoic areas surrounding the main pancreatic duct irregularities were observedmore frequently in high-grade pancreatic intraepithelial neoplasia (82.8%) and pancreatic ductal adenocarcinoma ≤10 mm (90.9%) than in benign stenosis (15.0%) (p<0.001). High-grade pan-creatic intraepithelial neoplasia exhibited mottled hypoechoic areas more frequently (79.3% vs 18.9%, p<0.001), and round hypoechoic areas less frequently (3.4% vs 72.7%, p<0.001), than pancreatic ductal adenocarcinoma ≤10 mm. The sensitivity and specificity of hypoechoic areas for differentiating high-grade pancreatic intraepithelial neoplasia, pancreatic ductal adenocarci-noma ≤10 mm, and benign stenosis were both 85.0%, with moderate interobserver agreement. Conclusions The hypoechoic areas surrounding main pancreatic duct irregularities on endo-scopic ultrasound may differentiate between high-grade pancreatic intraepithelial neoplasia, pan-creatic ductal adenocarcinoma ≤10 mm, and benign stenosis (Trial Registration: UMIN Clinical Trials Registry (UMIN000044789).

Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN) in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. Methods: We retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiated NEC (PDNEC), the latter further subdivided into large and small cell type. Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the median tumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7 PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes. Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4) vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% - 95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); response rates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) and median survival, 227 vs. 186 days (P = 0.227). Conclusions: The WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing Ki67 and KRAS mutation profiles, and distinct response to chemotherapy. Further studies for the re-evaluation of the current WHO 2010 classification is warranted.

Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN)in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67labeling index (LI). However, the clinical behavior of NEC is still not fully studied.We aimed to clarify the clinicopathological and molecular characteristics ofNECs.Methods: We retrospectively evaluated the clinicopathological characteristics,KRAS mutation status, treatment response, and the overall survival of elevenpNEC patients diagnosed between 2001 and 2014 according to the WHO 2010.We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiatedNEC (PDNEC), the latter further subdivided into large and smallcell type.Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the mediantumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes.Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4)vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% -95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); responserates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) andmedian survival, 227 vs. 186 days (P = 0.227).Conclusions: The WHO-NEC category may be composed of heterogeneousdisease entities, namely WDNEC and PDNEC. These subgroups tended to exhibitdiffering Ki67 and KRAS mutation profiles, and distinct response to chemotherapy.Further studies for the re-evaluation of the current WHO 2010 classification iswarranted.

BACKGROUND: Both endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) and tumor ablation using ethanol are very common procedures, and the utility of these therapies has already been reported in prominent journals. However, their effectiveness appears temporary and insufficient, especially EUS-CPN. We therefore have to consider new reagents for improving the results. The present study examined the best concentration of ethanol and povidone iodine mixed with atelocollagen for more effective therapies. METHODS: The effects of the new reagents were confirmed in three live pigs. At first, we injected three kinds of reagents (including indigo carmine) in three separate areas of para-aortic tissue under EUS guidance in one pig. At more than 4 hours after injection, we checked ethanol injection sites after dissection. In next study, we performed EUS-guided injection of a total of six kinds of reagents (two kinds of ethanol, three kinds of povidone iodine, and control atelocollagen) into the livers of two living pigs. After 2 weeks, we examined tissue damage to the liver in the two pigs. RESULTS: The 75% ethanol (absolute ethanol 3.75 mL + 1% atelocollagen 1.25 mL + a very small amount of indigo carmine) was seen like blue gel, and still remained in the para-aortic tissue. Brownish areas of povidone iodine mixed with 3% atelocollagen exhibited clear, regular borders with greatly reduced infiltration into surrounding tissue compared to others. CONCLUSION: We concluded that 75% ethanol mixed with 1% atelocollagen appears optimal for EUS-CPN. Povidone iodine mixed with 3% atelocollagen may be suitable for small tumor ablation therapy.
Celiac Plexus* ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Endosonography ; Ethanol ; Indicators and Reagents ; Indigo Carmine ; Liver ; Povidone-Iodine ; Swine

Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.
Biopsy, Fine-Needle ; Cholangiopancreatography, Endoscopic Retrograde ; Choledochostomy ; Dioxolanes ; Drainage ; Endoscopy ; Endosonography ; Fluorocarbons ; Humans ; Jaundice, Obstructive ; Transducers