The read-through transcription-mediated autoactivation circuit for virulence regulator expression drives robust type III secretion system 2 expression in Vibrio parahaemolyticus.

Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis in humans worldwide. The major virulence factor responsible for the enteropathogenicity of this pathogen is type III secretion system 2 (T3SS2), which is encoded on the 80-kb V. parahaemolyticus pathogenicity island (Vp-PAI), the gene expression of which is governed by the OmpR-family transcriptional regulator VtrB. Here, we found a positive autoregulatory feature of vtrB transcription, which is often observed with transcriptional regulators of bacteria, but the regulation was not canonically dependent on its own promoter. Instead, this autoactivation was induced by heterogeneous transcripts derived from the VtrB-regulated operon upstream of vtrB. VtrB-activated transcription overcame the intrinsic terminator downstream of the operon, resulting in transcription read-through with read-in transcription of the vtrB gene and thus completing the autoregulatory loop for vtrB gene expression. The dampening of read-through transcription with an exogenous strong terminator reduced vtrB gene expression. Furthermore, a V. parahaemolyticus mutant with defects in the vtrB autoregulatory loop also showed compromises in T3SS2 expression and T3SS2-dependent cytotoxicity in vitro and enterotoxicity in vivo, indicating that this autoregulatory loop is essential for sustained vtrB activation and the consequent robust expression of T3SS2 genes for pathogenicity. Taken together, these findings demonstrate that the regulatory loop for vtrB gene expression based on read-through transcription from the upstream operon is a crucial pathway in T3SS2 gene regulatory network to ensure T3SS2-mediated virulence of V. parahaemolyticus.

The Xenogeneic Silencer Histone-Like Nucleoid-Structuring Protein Mediates the Temperature and Salinity-Dependent Regulation of the Type III Secretion System 2 in Vibrio parahaemolyticus.

The marine bacterium Vibrio parahaemolyticus is a major seafood-borne pathogen that causes acute diarrhea in humans. A crucial virulence determinant of V. parahaemolyticus is the type III secretion system 2 (T3SS2), which is encoded on the Vibrio parahaemolyticus pathogenicity island (Vp-PAI), in which gene expression is dependent on environmental cues, such as temperature and salinity. This characteristic may implicate the adaptation of V. parahaemolyticus from its natural habitat to the human body environment during infection; however, the underlying mechanism remains unknown. Here, we describe the regulatory role of the histone-like nucleoid-structuring protein (H-NS), which is a xenogeneic silencing protein, in T3SS2 gene expression through the conditional silencing of the gene encoding a master regulator of Vp-PAI, VtrB. The hns deletion canceled the temperature- and salinity-dependent differential T3SS2 gene expression. H-NS bound to the vtrB promoter containing AT-rich sequences, and the binding sites partially overlapped the binding sites of two positive regulators of vtrB (i.e., VtrA and ToxR), which may block the transcriptional activation of vtrB. H-NS-family proteins multimerize along the DNA strand, forming stiffened filament and/or bridging DNA duplexes for its target silencing. In V. parahaemolyticus, mutations at conserved residues that are required for the multimerization of H-NS abolished the repressive activity on VtrB expression, supporting the contention that H-NS multimerization is also critical for vtrB silencing in V. parahaemolyticus. Taken together, these findings demonstrate the principal role of H-NS as a thermal and salt switch with sensory and regulatory properties for ensuring T3SS2 gene regulation in V. parahaemolyticus. IMPORTANCE In the major seafood-borne pathogen Vibrio parahaemolyticus, the type III secretion system 2 (T3SS2) is a major virulence factor that is responsible for the enterotoxicity of this bacterium. The expression of T3SS2 varies according to changes in temperature and salinity, but the mechanism via which T3SS2 expression is regulated in response to such physical cues remains unknown. Here, we report that H-NS, a xenogeneic silencer that is widespread in Gram-negative bacteria, modulates the entirety of T3SS2 gene expression through the transcriptional silencing of the gene encoding the T3SS2 master regulator VtrB in a temperature- and salinity-dependent manner. Thus, our findings provide insights into how this pathogen achieves the appropriate control of the expression of virulence genes in the transition between aquatic and human environments.

Direct RNA Sequencing Unfolds the Complex Transcriptome of Vibrio parahaemolyticus.

Conventional bacterial genome annotation provides information about coding sequences but ignores untranslated regions and operons. However, untranslated regions contain important regulatory elements as well as targets for many regulatory factors, such as small RNAs. Operon maps are also essential for functional gene analysis. In the last decade, considerable progress has been made in the study of bacterial transcriptomes through transcriptome sequencing (RNA-seq). Given the compact nature of bacterial genomes, many challenges still cannot be resolved through short reads generated using classical RNA-seq because of fragmentation and loss of the full-length information. Direct RNA sequencing is a technology that sequences the native RNA directly without information loss or bias. Here, we employed direct RNA sequencing to annotate the Vibrio parahaemolyticus transcriptome with its full features, including transcription start sites (TSSs), transcription termination sites, and operon maps. A total of 4,103 TSSs were identified. In comparison to short-read sequencing, full-length information provided a deeper view of TSS classification, showing that most internal and antisense TSSs were actually a result of gene overlap. Sequencing the transcriptome of V. parahaemolyticus grown with bile allowed us to study the landscape of pathogenicity island Vp-PAI. Some genes in this region were reannotated, providing more accurate annotation to increase precision in their characterization. Quantitative detection of operons in V. parahaemolyticus showed high complexity in some operons, shedding light on a greater extent of regulation within the same operon. Our study using direct RNA sequencing provides a quantitative and high-resolution landscape of the V. parahaemolyticus transcriptome. IMPORTANCE Vibrio parahaemolyticus is a halophilic bacterium found in the marine environment. Outbreaks of gastroenteritis resulting from seafood poisoning by these pathogens have risen over the past 2 decades. Upon ingestion by humans-often through the consumption of raw or undercooked seafood-V. parahaemolyticus senses the host environment and expresses numerous genes, the products of which synergize to synthesize and secrete toxins that can cause acute gastroenteritis. To understand the regulation of such adaptive response, mRNA transcripts must be mapped accurately. However, due to the limitations of common sequencing methods, not all features of bacterial transcriptomes are always reported. We applied direct RNA sequencing to analyze the V. parahaemolyticus transcriptome. Mapping the full features of the transcriptome is anticipated to enhance our understanding of gene regulation in this bacterium and provides a data set for future work. Additionally, this study reveals a deeper view of a complicated transcriptome landscape, demonstrating the importance of applying such methods to other bacterial models.

Diversity in Sensing and Signaling of Bacterial Sensor Histidine Kinases.

Two-component signal transduction systems (TCSs) are widely conserved in bacteria to respond to and adapt to the changing environment. Since TCSs are also involved in controlling the expression of virulence, biofilm formation, quorum sensing, and antimicrobial resistance in pathogens, they serve as candidates for novel drug targets. TCSs consist of a sensor histidine kinase (HK) and its cognate response regulator (RR). Upon perception of a signal, HKs autophosphorylate their conserved histidine residues, followed by phosphotransfer to their partner RRs. The phosphorylated RRs mostly function as transcriptional regulators and control the expression of genes necessary for stress response. HKs sense their specific signals not only in their extracytoplasmic sensor domain but also in their cytoplasmic and transmembrane domains. The signals are sensed either directly or indirectly via cofactors and accessory proteins. Accumulating evidence shows that a single HK can sense and respond to multiple signals in different domains. The underlying molecular mechanisms of how HK activity is controlled by these signals have been extensively studied both biochemically and structurally. In this article, we introduce the wide diversity of signal perception in different domains of HKs, together with their recently clarified structures and molecular mechanisms.

Risk of colonoscopic post-polypectomy bleeding in patients after the discontinuation of antithrombotic therapy.

BACKGROUND/AIMS: Few studies have examined the incidence of post-polypectomy bleeding (PPB) after discontinuation of antithrombotic therapies. Therefore, this study aimed to evaluate the incidence of PPB and thromboembolic events in patients whose antithrombotic agents were discontinued before colonoscopy. MATERIALS AND METHODS: We retrospectively selected all patients who underwent colon polypectomy at a community hospital. A total of 282 patients (540 polypectomies) discontinued antithrombotic agents (group 1), and 1,648 patients (2,827 polypectomies) did not take antithrombotic agents (group 2). The cessation periods before and after polypectomies were 4 and 3 days for warfarin, 5 and 3 days for anti-platelet agents, and 7 and 5 days of combination therapy, respectively. Main outcome measurements were the incidence of PPB and thromboembolic events. RESULTS: Immediate PPB rates were 3.9% (11/282) in group 1 and 4.6% (76/1648) in group 2 (adjusted odds ratio [OR], 0.85; 95% confidence interval [CI], 0.42-1.72; p=0.65). Delayed PPB rates were 1.4% (4/282) in group 1 and 1.1% (18/1648) in group 2 (adjusted OR, 1.24; 95% CI, 0.36-4.24; p=0.732). No thromboembolic events were observed in either group. CONCLUSION: Our cessation periods were appropriate, and further shortening of these periods is possible.

Multicenter prospective study on the histological diagnosis of gastric cancer by narrow band imaging-magnified endoscopy with and without acetic acid.

Background and study aims The usefulness of endoscopy for diagnosing histological type remains unclear. This study aimed to examine the diagnostic accuracy of white light endoscopy (WLE), magnified endoscopy with narrow band imaging (NBI-ME), and NBI-ME with acetic acid enhancement (NBI-AA) for histological type of gastric cancer. Patients and methods Patients with depressed-type gastric cancers resected by endoscopic submucosal dissection were prospectively enrolled, and 221 cases were analyzed. Histological type was diagnosed by WLE, followed by NBI-ME and NBI-AA. Histological type was classified into differentiated adenocarcinoma and undifferentiated adenocarcinoma. Histological type was diagnosed based on lesion color in WLE, surface patterns (pit, villi, and unclear) and vascular irregularities in NBI-ME, and surface patterns in NBI-AA. Results Histological types of target areas were differentiated adenocarcinoma and undifferentiated adenocarcinoma in 206 and 15 cases, respectively. Diagnostic accuracy of WLE, NBI-ME, and NBI-AA for the histological type was 96.4 % (213/221), 96.8 % (214/221), and 95.5 % (211/221), respectively. No significant differences were observed among modalities. Positive predictive value based on endoscopic findings in NBI-ME was 98.0 % (149/152) for the villi pattern, 100 % (19/19) for the irregular pit pattern, 100 % (9/9) for the unclear surface pattern with a vascular network, 90.3 % (28/31) for the unclear surface pattern with mild vascular irregularity, and 88.9 % (8/9) for the unclear surface pattern with severe vascular irregularity. Conclusions NBI-ME and NBI-AA did not show any advantages over WLE for diagnostic accuracy. Villi pattern, irregular pit pattern, and vascular network may be useful for identifying differentiated adenocarcinoma.

Identification of an internal cavity in the PhoQ sensor domain for PhoQ activity and SafA-mediated control.

The PhoQ/PhoP two-component signal transduction system is conserved in various Gram-negative bacteria and is often involved in the expression of virulence in pathogens. The small inner membrane protein SafA activates PhoQ in Escherichia coli independently from other known signals that control PhoQ activity. We have previously shown that SafA directly interacts with the sensor domain of the periplasmic region of PhoQ (PhoQ-SD) for activation, and that a D179R mutation in PhoQ-SD attenuates PhoQ activation by SafA. In this study, structural comparison of wild-type PhoQ-SD and D179R revealed a difference in the cavity (SD (sensory domain) pocket) found in the central core of this domain. This was the only structural difference between the two proteins. Site-directed mutagenesis of the residues surrounding the SD pocket has supported the SD pocket as a site involved in PhoQ activity. Furthermore, the SD pocket has also been shown to be involved in SafA-mediated PhoQ control.

Identification and characterization of a translation arrest motif in VemP by systematic mutational analysis.

VemP ( Vibrio protein export monitoring polypeptide) is a secretory protein comprising 159 amino acid residues, which functions as a secretion monitor in Vibrio and regulates expression of the downstream V.secDF2 genes. When VemP export is compromised, its translation specifically undergoes elongation arrest at the position where the Gln156 codon of vemP encounters the P-site in the translating ribosome, resulting in up-regulation of V.SecDF2 production. Although our previous study suggests that many residues in a highly conserved C-terminal 20-residue region of VemP contribute to its elongation arrest, the exact role of each residue remains unclear. Here, we constructed a reporter system to easily and exactly monitor the in vivo arrest efficiency of VemP. Using this reporter system, we systematically performed a mutational analysis of the 20 residues (His138-Phe157) to identify and characterize the arrest motif. Our results show that 15 residues in the conserved region participate in elongation arrest and that multiple interactions between important residues in VemP and in the interior of the exit tunnel contribute to the elongation arrest of VemP. The arrangement of these important residues induced by specific secondary structures in the ribosomal tunnel is critical for the arrest. Pro scanning analysis of the preceding segment (Met120-Phe137) revealed a minor role of this region in the arrest. Considering these results, we conclude that the arrest motif in VemP is mainly composed of the highly conserved multiple residues in the C-terminal region.

Gastroduodenal Intussusception with a Gastric Gastrointestinal Stromal Tumor Treated by Endoscopic Submucosal Dissection.

A 95-year-old Japanese woman presented to our hospital with intermittent vomiting and several episodes of melena. Abdominal computed tomography revealed intussusception of the gastric tumor into the duodenum. After endoscopic reduction, endoscopic ultrasonography identified a hypoechogenic lesion limited to the submucosal layer. Endoscopic resection was performed as a localized treatment for the prevention of recurrent gastroduodenal intussusception. To our knowledge, there have been no other reports describing a gastric gastrointestinal stromal tumor presenting with gastroduodenal intussusception and treated using an endoscopic submucosal dissection technique.

Nascent chain-monitored remodeling of the Sec machinery for salinity adaptation of marine bacteria.

SecDF interacts with the SecYEG translocon in bacteria and enhances protein export in a proton-motive-force-dependent manner. Vibrio alginolyticus, a marine-estuarine bacterium, contains two SecDF paralogs, V.SecDF1 and V.SecDF2. Here, we show that the export-enhancing function of V.SecDF1 requires Na+ instead of H+, whereas V.SecDF2 is Na+-independent, presumably requiring H+. In accord with the cation-preference difference, V.SecDF2 was only expressed under limited Na+ concentrations whereas V.SecDF1 was constitutive. However, it is not the decreased concentration of Na+ per se that the bacterium senses to up-regulate the V.SecDF2 expression, because marked up-regulation of the V.SecDF2 synthesis was observed irrespective of Na+ concentrations under certain genetic/physiological conditions: (i) when the secDF1VA gene was deleted and (ii) whenever the Sec export machinery was inhibited. VemP (Vibrio export monitoring polypeptide), a secretory polypeptide encoded by the upstream ORF of secDF2VA, plays the primary role in this regulation by undergoing regulated translational elongation arrest, which leads to unfolding of the Shine-Dalgarno sequence for translation of secDF2VA. Genetic analysis of V. alginolyticus established that the VemP-mediated regulation of SecDF2 is essential for the survival of this marine bacterium in low-salinity environments. These results reveal that a class of marine bacteria exploits nascent-chain ribosome interactions to optimize their protein export pathways to propagate efficiently under different ionic environments that they face in their life cycles.

Solubility of Carbon Dioxide in Pentaerythritol Hexanoate: Molecular Dynamics Simulation of a Refrigerant-Lubricant Oil System.

We have investigated the solubility and the solvation structure between a refrigerant (carbon dioxide, CO2) and a lubricant oil (pentaerythritol hexanoate, PEC6) by molecular dynamics simulations. First, to investigate the solubility, we calculated the vapor-liquid equilibrium pressure. The chemical potential of the liquid phase and the gas phase were calculated, and the equilibrium state was obtained from the crossing point of these chemical potentials. The equilibrium pressures agreed well with experimental data over a wide range of temperatures and mole fractions of CO2. Second, the solvation structure was also investigated on a molecular scale. We found the following characteristics. First, the tails of the lubricant oil are relatively rigid inside the ester groups but flexible beyond. Second, CO2 molecules barely enter the lubricant core as delimited by the ester groups. Third, the double-bonded oxygen atoms of the ester groups are good sorption sites for CO2. Fourth, only a few CO2 molecules are attached to more than one carbonyl oxygen simultaneously. Finally, there is also significant unspecific sorption of CO2 in the alkane tail region. These results indicate that increasing the size of the rigid lubricant core would probably decrease the solubility, whereas increasing the number of polar groups would increase it.

Lymph node metastasis after endoscopic submucosal dissection of a differentiated gastric cancer confined to the mucosa with an ulcer smaller than 30 mm.

In the expanded indications for endoscopic resection, Japanese guidelines for gastric cancer include differentiated cancers confined to the mucosa with an ulcer <30 mm. We describe a patient with lymph node metastasis after curative endoscopic submucosal dissection (ESD) for a tumor of this indication. The patient was a 70-year-old man with chronic hepatitis C. He underwent ESD for early gastric cancer in May 2010. Pathology revealed a moderately differentiated adenocarcinoma, 22 × 17 mm in size, that was confined to the mucosa with an ulcer. The horizontal and vertical margins were negative for the tumor. We diagnosed thiscase as curative resection of expanded indication and followed this patient with endoscopy, abdominal ultrasonography (AUS) or enhanced computed tomography (CT) approximately every 6 months. After 17 months, lymph node metastasis was detected with AUS and CT and diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy in August 2011. Distal gastrectomy with D2 dissection was carried out in December 2011. Although it is low, the possibility of recurrence should be borne in mind after endoscopic treatment of early gastric cancer, despite its inclusion in the expanded indications for endoscopic resection.

Gastrointestinal stromal tumor of the ampulla of Vater: a case report.

Gastrointestinal stromal tumors (GISTs) usually develop in the stomach and small intestine and only rarely occur at the ampulla of Vater, with only 11 cases reported in the literature. We report a case of a GIST of the ampulla of Vater. A 36-year-old, previously healthy man presented with a loss of consciousness lasting a few minutes. A gastroduodenal endoscopy revealed a submucosal tumor with central ulceration at the ampulla of Vater. The enhanced computed tomography scan revealed a smooth-outlined hypervascular solid mass (24 mm × 30 mm) in the second part of the duodenum. Neither lymphadenopathy nor metastasis was observed. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed normal bile and pancreatic ducts. Biopsies were collected from the ulcerative lesion, and the tumor was diagnosed as a GIST. A submucosal tumor with central ulceration may be a characteristic form of GISTs of the ampulla of Vater, and biopsy studies are useful for the diagnosing such tumors. The patient underwent pancreatoduodenectomy, and the operative specimen revealed a 2.2-cm GIST with 1 mitosis per 50 high-power fields. The gold standard for treatment of GISTs is surgical resection without rupture of a capsule. If technically possible, local resection may be considered. However, when the location of the lesion presents challenges, a pancreatoduodenectomy should be performed for GIST of the ampulla of Vater.

Endoscopic retrograde cholangiopancreatography using a cap-assisted highly flexible colonoscope in patients with Roux-en-Y anastomosis.

In this retrospective study of 10 patients with Roux-en-Y anastomosis, endoscopic retrograde cholangiopancreatography (ERCP) using a cap-assisted thin highly flexible colonoscope was done for treatment of bile duct stones. In five patients, the papilla of Vater was successfully reached using the colonoscope alone. However, in the other five patients, combination with an overtube was needed to reach the papilla. In all cases, complete removal of bile duct stones was accomplished. Procedure-related adverse events occurred in two cases. In conclusion, use of a cap-assisted thin highly flexible colonoscope for ERCP was successful in patients with a Roux-en-Y anastomosis.

Molecular genotyping of anisakis larvae in Middle Eastern Japan and endoscopic evidence for preferential penetration of normal over atrophic mucosa.

BACKGROUND: Anisakiasis is a parasitic disease caused primarily by Anisakis spp. larvae in Asia and in Western countries. The aim of this study was to investigate the genotype of Anisakis larvae endoscopically removed from Middle Eastern Japanese patients and to determine whether mucosal atrophy affects the risk of penetration in gastric anisakiasis. METHODS: In this study, 57 larvae collected from 44 patients with anisakiasis (42 gastric and 2 colonic anisakiasis) were analyzed retrospectively. Genotyping was confirmed by restriction fragment length polymorphism (RFLP) analysis of ITS regions and by sequencing the mitochondrial small subunit (SSU) region. In the cases of gastric anisakiasis, correlation analyses were conducted between the frequency of larval penetration in normal/atrophic area and the manifestation of clinical symptoms. RESULTS: Nearly all larvae were A. simplex seusu stricto (s.s.) (99%), and one larva displayed a hybrid genotype. The A. simplex larvae penetrated normal mucosa more frequently than atrophic area (p = 0.005). Finally, patients with normal mucosa infection were more likely to exhibit clinical symptoms than those with atrophic mucosa infection (odds ratio, 6.96; 95% confidence interval, 1.52-31.8). CONCLUSIONS: In Japan, A. simplex s.s. is the main etiological agent of human anisakiasis and tends to penetrate normal gastric mucosa. Careful endoscopic examination of normal gastric mucosa, particularly in the greater curvature of the stomach will improve the detection of Anisakis larvae.

Pseudoaneurysm caused by a self-expandable metal stent: a report of three cases.

We present three cases of pseudoaneurysm caused by self-expandable metal stents that formed arteriobiliary fistulas and caused hemobilia. Diagnoses were made on the basis of dynamic computed tomography or angiography. One patient died because of bleeding and cholangitis, whereas the others were successfully treated by transarterial embolization.

A case of primary pancreatic lymphoblastic lymphoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Pancreatic involvement is an extremely rare manifestation of lymphoblastic lymphoma (LBL), and only a few cases have been reported. We report a case of LBL arising from the pancreas that was diagnosed using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The patient was a 57-year-old female who had suffered from abdominal pain for 2 weeks. A physical examination revealed an upper abdominal mass, but did not detect peripheral lymphadenopathy. Imaging studies including computed tomography (CT) and (18)F-fluorodeoxy glucose (FDG)-positron emission tomography-CT revealed an enlarged pancreatic body, which was positive for FDG uptake. EUS-FNA detected medium-sized proliferating atypical lymphocytes, and immunohistochemical staining demonstrated that these cells were positive for CD20, CD10, PAX5, and terminal deoxynucleotidyl transferase. A bone marrow examination was negative for lymphoma infiltration, and a diagnosis of LBL arising from the pancreas was made. The patient was successfully treated with a combination of chemotherapy and pancreatic irradiation.

Mechanism of activation of PhoQ/PhoP two-component signal transduction by SafA, an auxiliary protein of PhoQ histidine kinase in Escherichia coli.

The PhoQ/PhoP two-component signal transduction system in Escherichia coli is activated by SafA, a small membrane protein that modifies the PhoQ histidine kinase. The SafA C-terminal domain (41-65 aa) interacts directly with the sensory domain of PhoQ at the periplasm. We used in vitro and in vivo strategies to elucidate the way SafA modifies the PhoQ/PhoP phosphorelay system. First, the enzymatic activities of membranes from cells overexpressing PhoQ and cells expressing both PhoQ and SafA were compared in vitro. Increased autophosphorylation of PhoQ was observed in the presence of SafA, but it did not increase the dephosphorylation of phospho-PhoP by PhoQ. In addition, SafA increased the phospho-PhoP level on the phosphotransfer assay. We confirmed that induction of SafA results in an accumulation of phospho-PhoP in vivo by the Phos-tag system. Our results suggest that the accumulation of phospho-PhoP is linked to activation of PhoQ autophosphorylation by SafA.

A case of focal autoimmune pancreatitis (AIP) mimicking an intraductal papillary mucinous neoplasm (IPMN).

The present case involved a 76-year-old man with a cystic mass in the head of his pancreas. The cystic lesion, which measured 17.7 × 9.8 mm, was first detected by ultrasonography (US) at the age of 72 years. Follow-up endoscopic ultrasonography (EUS) performed at 4 years after the lesion had first been detected revealed a mural nodule measuring 14.0 × 8.4 mm in the cyst. Endoscopic retrograde pancreatography (ERP) imaging revealed that the main pancreatic duct was in communication with the cyst and that there was no irregular narrowing of the main pancreatic duct. On the basis of these results, the patient was diagnosed with an intraductal papillary mucinous neoplasm (IPMN), and stomach-preserving pancreaticoduodenectomy was performed. A histopathological examination revealed that the interior of the cystic part of the lesion was lined by a pancreatic ductal epithelium. A pathological examination of the nodular lesion detected storiform fibrosis, severe lymphoplasmacytic infiltration, and hyperplasia in the pancreatic duct epithelium together with a small amount of mucus. On immunohistological staining, the infiltrating lymphoplasmacytes were found to be positive for IgG4. Accordingly, the patient was diagnosed with focal autoimmune pancreatitis (AIP). In conclusion, we reported a case of focal AIP mimicking IPMN. This case showed neither enlargement of the pancreas nor irregular narrowing of the main pancreatic duct.