Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.

Radiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis. Data on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC. FPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P < 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16-63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved. The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P < 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia. FPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.

Understanding the pathogenesis and carcinogenesis of gallbladder adenocarcinoma is important. The fifth edition of the World Health Organization’s tumor classification of the digestive system indicates three types of preinvasive neoplasm of the gallbladder: pyloric gland adenoma (PGA), biliary intraepithelial neoplasia (BilIN), and intracholecystic papillary neoplasm (ICPN). New terminologies have also been introduced, such as intracholecystic papillary-tubular neoplasm, gastric pyloric, simple mucinous type, and intracholecystic tubular non-mucinous neoplasm (ICTN). Pancreatobiliary maljunction (PBM) poses a markedly high risk for bile duct carcinoma, which was analyzed and investigated mainly by Asian researchers in the past; however, recent studies have clarified a similar significance of biliary carcinogenesis in Western countries as well. In this study, we reviewed and summarized information on three gallbladder neoplastic precursors, PGA, BilIN, and ICPN, and gallbladder lesions in patients with PBM.

Backgrounds: Endoscopic ultrasonography (EUS) is used to observe the stricture of the main pancreatic duct (MPD) and in diagnosing pancreatic cancer (PC). We investigate the findings on EUS by referring to the histopathological findings of resected specimens. Materials and Methods: Six patients with carcinoma in situ (CIS) and 30 patients with invasive carcinoma of 20 mm or less were included. The preoperative EUS findings were classified as follows. A1: Simple stricture type—no findings around the stricture; A2: Hypoecho stricture type—localized hypoechoic area without demarcation around the stricture; A3: Tumor stricture type—tumor on the stricture; B: Dilation type—the dilation of the pancreatic duct without a downstream stricture; C: Parenchymal tumor type—tumor located apart from the MPD. Results: Classes A1 and A2 consisted of 2 CISs, and 4 invasive carcinomas included two cases smaller than 5 mm in diameter. Most of the cancers classified as A3 or C were of invasive carcinoma larger than 5 mm in diameter. All cancers classified as B involved CIS. Serial pancreatic-juice aspiration cytologic examination (SPACE) was selected for all types of cases, with a sensitivity of 92.0%, while EUS-guided fine needle aspiration cytology (EUS-FNA) was only useful for invasive carcinoma, and its sensitivity was 66.7%. Conclusions: Stricture without a tumor could be a finding for invasive PC and pancreatic duct dilation without a downstream stricture could be a finding indicative of CIS. Carcinoma smaller than 5 mm in diameter could not be recognized by EUS. SPACE had a high sensitivity for diagnosing small PC.