Clinicopathological study of surgically treated non-neoplastic diseases of the pancreas with special reference to autoimmune pancreatitis.

PURPOSE: After the popularization of serum immunoglobulin G4 (IgG4) measurement and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in our institute, surgical resection for non-neoplastic diseases of the pancreas became less common. Although the incidence of such false-positive cases was clarified in the 10-year period after the introduction of these measures (2009-2018), these data were not compared with the 30 years before 2009 (1979-2008). This study was performed to determine the percentage of autoimmune pancreatitis (AIP) that was included during the latter period and how the numbers of false-positive cases differed between the two periods. METHODS: From 1979 to 2008, 51 patients had clinical suspicion of pancreatic carcinoma (false-positive disease). Among these 51 patients, 32 non-alcoholic patients who had tumor-forming chronic pancreatitis (TFCP) were clinically, histologically, and immunohistochemically compared with 11 patients who had TFCP during the latter 10-year period. RESULTS: Retrospective IgG4 immunostaining of false-positive TFCP revealed 14 (35.0%) cases of AIP in the former 30 years versus 5 (45.5%) in the latter 10 years. There were 40 (5.9%) cases of TFCP among 675 patients in the former 30 years and 11 (0.9%) among 1289 patients in the latter 10 years. CONCLUSIONS: When the TFCP ratio of pancreatic resections and the AIP ratio of false-positive TFCPs were compared between the two periods, the TFCP ratio was 5.9% versus 0.9% and the AIP ratio was 35.0% versus 45.5%, respectively. It can thus be speculated that IgG4 measurement and EUS-FNA are absolutely imperative for the diagnosis of TFCP.

Widespread and multifocal carcinomas in situ (CISs) through almost the entire pancreas: report of a case with preoperative cytological diagnosis.

PURPOSE: It is imperative for prognostic improvement of pancreatic cancer that we try to diagnose carcinoma in situ (CIS) of lesions, i.e., precursors of invasive ductal carcinomas (IDCs) at an early stage, because results of treatment of patients with IDCs themselves continue to be rather unsatisfactory. MATERIALS AND RESULTS: We report here a case of a patient who received subtotal pancreatectomy for widespread and multifocal CISs of the pancreas after preoperative brushing cytology from the epithelium of dilated main pancreatic duct proved cancer-positive preoperatively. CONCLUSIONS: From our experience, we conclude that examination for CIS of the pancreas must be recommended whenever dilatation of relatively large pancreatic ducts is found by ultrasound or computed tomography. We should therefore advance to magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography and then cytological and/or pathological assessment of the pancreatic duct whenever non-continuous narrowing, localized dilatation, or other irregularities are encountered.

Pancreatogram findings for carcinoma in situ (CIS) of the pancreas seen on endoscopic retrograde cholangiopancreatography and postoperative pancreatography of resected specimens: can CIS be diagnosed preoperatively?

BACKGROUND/AIMS: From 1992 to 2003, 7 carcinomata in situ (CIS) were incidentally discovered during microscopical observation of resected materials for advanced carcinomas of peripancreatic organs, of which 4 had undergone endoscopic retrograde cholangiopancreatography (ERCP) or postoperative pancreatography of the resected specimen (POP). In addition, 7 of 79 invasive ductal carcinomata (IDC) of the pancreas were accompanied by CIS > or =2 cm long. A total of 11 patients were reviewed here for pancreatographic findings for CIS of the pancreas. METHODS: All resected pancreatobiliary materials were sliced serially at 5- to 8-mm intervals in a plane at right angles to the main pancreatic duct, referring to POP images. RESULTS: Irregularity (I), non-continuous narrowing (N), granular defects (G), and dilatation (D) were seen in 78, 67, 33 and 22% on ERCP, respectively, and in 90, 70, 60 and 40% on POP, respectively. CONCLUSIONS: I, N, G, and D are most important pancreatographic findings in ERCP and highly suggestive of CIS of the pancreas, so that whenever they are encountered, cytological and/or pathological examination of the pancreatic duct should be actively performed.

Image-diagnostic features of mature cystic teratomas of the pancreas: report on two cases difficult to diagnose preoperatively.

This report documents the findings of two rare cases of mature cystic teratoma of the pancreas. Although they could not be diagnosed preoperatively, our retrospective report suggests that the combined diagnosis of ultrasonography (US), enhanced computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) might allow differentiation from other cystic lesions such as mucinous cystic tumors (MCTs) and intraductal papillary-mucinous tumors (IPMTs). Since the cystic teratomas were both filled with keratinous and sebaceous material, they were echogenic, appearing as solid masses on US. Enhanced CT showed their cystic nature, with values slightly higher than water, and MRCP revealed defects of internal signals.

Clinicopathology of pancreaticobiliary maljunction: relationship between alterations in background biliary epithelium and neoplastic development.

BACKGROUND/PURPOSE: Between 1988 and 2003, 38 patients underwent biliary resection for pancreaticobiliary maljunction (PBM). We reviewed the histopathologic findings for the surgically resected specimens to compare the clinical and pathologic features and assess the relationship between changes in the background biliary epithelium and the development of neoplasms. METHODS: Papillary hyperplasia (PHP) seen in the biliary epithelium of patients with PBM, was classified into grades 0--III in the gallbladder and grades 0--II in the extrahepatic bile duct, according to the extent, and was assessed for links with tumors in the same specimens. RESULTS: The incidence of gallbladder carcinoma was 13/21 in grades I--II, versus 0/16 in grade III, while the incidence of bile duct carcinoma was 4/20 in grade I versus 0/5 in grade II. Furthermore, these incidences for patients below age 50 years and age 50 or older were 1/18 versus 12/20, and 0/14 versus 6/17, respectively. CONCLUSIONS: PHP of the biliary epithelium in PBM patients is an important precursor lesion, especially for gallbladder cancer, and the risk becomes greater with age, regardless of the type of pancreatobiliary junction (PBJ) and its location in the biliary tract.

Surgical treatment of intraductal papillary-mucinous tumor (IPMT) of the pancreas: operative indications based on surgico-pathologic study focusing on invasive carcinoma derived from IPMT.

BACKGROUND/PURPOSE: Between 1979 and 2000, 51 patients with intraductal papillary-mucinous tumor (IPMT) of the pancreas underwent surgical resection. METHODS: The patients were reviewed to disclose the surgical pathology of invasive carcinoma derived from IPMT and to determine the surgical indications for IPMT on the basis of the pathologic findings. RESULTS: The incidence of invasive carcinoma derived from IPMT according to the localization of the tumor was as follows: 4/9 (44%) in the main pancreatic duct (MPD type), 4/9 (44%) showing ductal spread from the MPD to branch ducts (mixed type), and 2/33 (6%) in the 2 branch duct (branch type). The maximal size of the intraductal spread of invasive carcinomas (8 of 18 cases in the MPD and mixed type together and 2 of 33 cases in the branch type) was as follows: 6/8 (75%) in the MPD and mixed type were over 6 cm in size, and the 2-branch-type invasive carcinomas were within the 3-cm size range. CONCLUSIONS: We concluded that for both invasive and noninvasive IPMTs, surgical resection was necessary for any MPD or mixed-type IPMTs, and that surgical resection was appropriate for branch-type lesions larger than or equal to 3 cm in diameter, or for lesions smaller than 3 cm showing rapid growth on clinical images.

The activation of caspase-3 and DNA fragmentation in B cells phagocytosed by macrophages.

Apoptotic signaling of mammalian cells involves two pathways: the death receptor and mitochondrial pathways. In this in vivo study, we investigated apoptotic signaling of B cells in mouse germinal centers (GCs) of gut-associated lymphoid tissues (GALTs) using transmission electron microscopy (TEM), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL), immunofluorescence of members of caspase family and cFLIP(L), and caspase activity assay. It was very difficult to ultrastructurally differentiate B cells undergoing apoptosis from B cells differentiating into memory cells or plasma cells among B cells constituting GCs. Isolated B cells in GCs showed no active form of caspase-3 or TUNEL immunoreactivity, but expressed cFLIP(L). Contrary to isolated B cells, apoptotic B cells phagocytosed by macrophages exhibited immunoreactivity of the active form of caspase-3 and TUNEL, but lacked the cFLIP(L) expression. The caspase activity assay in GALTs clearly showed intense activity of caspase-3, caspase-9, and caspace-8 that was high in order. Therefore, the death receptor pathway accompanying the increased activity of caspase-3 and caspase-8 may be blocked by the expression of cFLIP(L) in B cells of GALTs. Moreover, both the activation of caspase-3 and DNA fragmentation first occur only when B cells are phagocytosed by macrophages.