A case of giant enteric muco-submucosal elongated polyp detected by melena.

A 78-year-old woman was admitted for examination and treatment of melena. Although upper and lower gastrointestinal endoscopy and abdominal computed tomography showed no bleeding lesions, oral double-balloon endoscopy revealed a long, slender polyp covered with normal mucosa and accompanied with erosions in the proximal jejunum. Surgical resection was successful. Histopathologically, the polyp was 125 mm in length and composed of edematous mucosa with dilated blood vessels. The growth was diagnosed as a rare enteric muco-submucosal elongated polyp. Her melena improved postoperatively.

Risk Factors for Pancreatic Stone Formation in Type 1 Autoimmune Pancreatitis: A Long-term Japanese Multicenter Analysis of 624 Patients.

OBJECTIVE: Autoimmune pancreatitis (AIP) has the potential to transform into chronic pancreatitis with pancreatic stone involvement. This retrospective investigation sought to clarify the risk factors for stone formation in type 1 AIP. METHODS: Questionnaires on patients with type 1 AIP were sent to 22 high-volume medical centers across Japan to compare the clinical features of patients with and without pancreatic stone formation. RESULTS: Of the completed records on 624 type 1 AIP patients, 31 (5%) had experienced pancreatic stones. Median follow-up duration was 1853 days. Bentiromide test values at diagnosis were significantly lower, and hemoglobin A1c values after corticosteroid treatment were significantly higher in patients with pancreatic stones. Imaging results disclosed that pancreatic atrophy and hilar or intrahepatic bile duct stenosis were significantly more frequent in patients with pancreatic stone formation. Pancreatic head swelling tended to be more frequent in this group as well. On the other hand, a shorter follow-up period was associated with the nonformation of pancreatic stones. CONCLUSIONS: The increased frequency of pancreatic head swelling in type 1 AIP patients exhibiting pancreatic stones indicated a propensity for pancreatic juice stasis with subsequent stone development and pancreatic dysfunction occurring over longer periods of disease duration.

Clinical course of type 1 autoimmune pancreatitis patients without steroid treatment: a Japanese multicenter study of 97 patients.

BACKGROUND: Sporadic autoimmune pancreatitis (AIP) cases showing remission without steroid treatment have been reported, however, the clinical course of these patients has not been clarified. This study sought to clarify the clinical course in AIP patients with hesitation for steroid treatment. METHODS: We collected clinical data for AIP patients from high-volume centers in Japan. Data for AIP patients with and those without steroid treatment (steroid treatment vs. wait and see policy or W&S) were then compared. The primary point was the relapse-free survival rate (RFS) in patients with and those without steroid treatment, as determined using Kaplan-Meier curve. The secondary point was the identification of predictors of remission and risks of relapse in AIP patients without steroid treatment. RESULTS: There were 510 AIP patients in the steroid treatment group and 97 patients in the W&S group. Overall, 55.7% (54/97) of type 1 AIP patients in the W&S group experienced transient remission without steroid treatment. The W&S group had a significantly higher patient age and significantly lower incidences of jaundice, diffuse pancreas swelling, proximal-type sclerosing cholangitis, and stent placement and a lower remission rate than the steroid treatment group (each P < 0.05). The RFS reached a plateau at 10 years in both the W&S group (50%) and steroid treatment group (52.9%). As for the RFS (W&S vs. group with steroid), 89.4% vs. 74.4% within 3 years, 81.8% vs. 65.3% within 5 years, and 50% vs. 52.9% within 10 years (log-rank, P = 0.064). Female gender (OR 0.340, P = 0.027) and stent placement for jaundice (OR 4.552, P = 0.008) were identified as predictors of transient remission in the W&S group. New-onset diabetes mellitus (OR 8.333, P = 0.012) and the presence of extensive multi-organ involvement (OR 35, P = 0.006) were identified as risks of relapse in the W&S group. CONCLUSION: Some type 1 AIP patients without steroid treatment experience transient remission. These cases tend to have lower disease activities than AIP patients receiving steroids. Female gender and stent placement for jaundice may be predictors of transient remission among patients not receiving steroid treatment, however, relapses can occur in these patients with new-onset diabetes mellitus and the presence of extensive multi-organ involvement. Therefore, steroid treatment is still imperative for these patients.

Low-dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis: a long-term Japanese multicenter analysis of 510 patients.

BACKGROUND: The effect of maintenance steroid treatment (MST) in reducing the risk of relapse in patients with autoimmune pancreatitis (AIP) remains under debate. The aim of this study was to validate the effect of MST on AIP administered in accordance with the 2010 Japanese consensus guidelines. METHODS: The clinical data of patients with (n = 510) from 22 high-volume centers in Japan were studied. The primary endpoints were the relapse rates (RRs) in patients administered MST versus those not administered MST. The secondary endpoints were the optimal dose and duration of MST in terms of steroid toxicity and the predictors of relapse. RESULTS: The RRs were 10.0% within 1 year, 25.8% within 3 years and 35.1% within 5 years. The RR in the steroid therapy group reached a plateau at 42.7% at 7 years. In terms of the optimal dosage, the overall RR in the MST 5 mg/day group was 26.1%, which was significantly lower than that in the group which had discontinued steroid therapy (45.2%; p = 0.023) or was receiving MST at 2.5 mg/day (43.4%, p = 0.001). The RRs in the group receiving MST at ≥5 mg/day versus the patient group receiving MST at <5 mg/day were 10.6 vs. 10.3% within 1 year, 23.5 vs. 32.9% within 3 years and 32.2 vs. 41.3% within 5 years, respectively (log-rank, p = 0.028). The best cutoff value of the total steroid dose for serious steroid toxicity was 6405 mg, with a moderate accuracy of 0.717 determined using the area under the curve. Presence of diffuse pancreatic swelling [odds ratio OR) 1.745; p = 0.008) and MST at >5 mg/day were identified as predictors of relapse (OR 0.483; p = 0.001). CONCLUSIONS: The RR could continue to increase for 7 years even under MST. Based on our analysis of the side effects of steroid therapy, MST at 5 mg/day for 2 (total 4625 mg) to 3 (total 6425 mg) years might be a rational and safe therapeutic strategy in terms of keeping the RR to <30% while avoiding potential steroid toxicity.

Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification.

OBJECTIVES: Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction. METHODS: Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R. RESULTS: The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 µg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 µU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP. CONCLUSIONS: Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

A case of simultaneous esophageal squamous cell carcinoma and Barrett's adenocarcinoma.

A 77-year-old male with a long history of alcohol consumption and smoking was admitted for hoarseness and dysphagia. Computed tomography revealed thickening of the middle intrathoracic esophageal wall and multiple mediastinal lymph node swellings. Esophagogastroduodenoscopic examination disclosed an advanced-stage squamous cell carcinoma lesion in the middle intrathoracic esophagus with synchronous early stage Barrett's adenocarcinoma. The patient underwent endoscopic submucosal dissection for the adenocarcinoma followed by chemoradiation therapy for the squamous cell carcinoma. In spite of their common risk factors, the simultaneous manifestation of esophageal squamous cell carcinoma and Barrett's adenocarcinoma is extremely rare and requires further study.

Case of Barrett's adenocarcinoma with marked endoscopic morphological changes in Barrett's esophagus over a long follow-up period of 15 years.

The natural history of Barrett's esophagus (BE) is unclear. We herein describe a case of Barrett's adenocarcinoma (BAC) in which we could closely observe marked morphological changes in BE over a long follow-up period of 15 years. A man in his seventies received routine esophagogastroduodenoscopy (EGD) and was diagnosed as having reflux esophagitis and short-segment BE. The BE gradually became elongated, and BAC was detected 9 years following the initial EGD examination with continued administration of a proton pump inhibitor. We witnessed that BE elongated sporadically over time and mucosal breaks of reflux esophagitis were detectable several years before elongation. The patient underwent endoscopic submucosal dissection for BAC and has been monitored by EGD every year thereafter. These remarkable morphological changes may be representative of the natural history of BE and aid in deciding long-term disease management.

The loop-forming method as a useful technique to rotate the endoscopic insertion tube shaft.

BACKGROUND AND STUDY AIMS: Gastroenterological endoscopists are instructed to bring the target to the 6-o'clock position when they take a biopsy specimen, use a snare, or cut a target organ. This action is performed primarily by rotating the shaft of the endoscopic insertion tube, which can be difficult in some situations when existing endoscopic methods are used. We previously described a method for optimal rotation of the endoscopic insertion tube shaft, called the loop-forming method (LFM). The present study aimed to validate this procedure and confirm the usefulness of the LFM for leftward rotation of the shaft. PARTICIPANTS AND METHODS: The LFM was specifically taught to 28 gastroenterological endoscopists, and the angle of rotation was measured before and after they received instruction in this method. RESULTS: The LFM significantly increased the average angle of leftward rotation from 266° to 327°. Moreover, whereas the instrument channel inlet tended to move away from the right hand of an operator using a conventional endoscopy method, it remained closely accessible to the right hand of an examiner using the LFM. CONCLUSIONS: The LFM has the potential to make endoscopic procedures easier and safer.

Helicobacter pylori-negative Differentiated Adenocarcinoma of the Stomach.

A 58-year-old Japanese man was diagnosed with differentiated adenocarcinoma of the stomach. Histological findings of the resected specimen revealed well- to moderately-differentiated tubular adenocarcinoma (tub1, tub2), 13 mm in diameter, which invaded into the submucosa (SM1, 300 µm) and lymphovascular lumen (ly1). Serum antibody against Helicobacter pylori (Hp) and the (13)C-urea breath test were negative, and there were no atrophic changes in the tumor-adjacent mucosa. The immunohistochemical analysis showed that gastric mucin (MUC5AC) was strongly positive and intestinal mucin (MUC2) was weakly and partially positive. According to these results, the final diagnosis of Hp-negative well-differentiated early gastric cancer was made.

Association Between Immunoglobulin G4-related Disease and Malignancy within 12 Years after Diagnosis: An Analysis after Longterm Followup.

OBJECTIVE: Because it is uncertain whether immunoglobulin G4-related disease (IgG4-RD) is associated with malignancy, we evaluated the incidence of cancer development in a large cohort of patients with IgG4-RD. METHODS: The study enrolled 158 patients diagnosed as having IgG4-RD between 1992 and 2012. We calculated the standardized incidence ratio (SIR) and cumulative rate of malignancies in this group and searched for risk factors associated with the occurrence of tumors. RESULTS: A total of 34 malignancies were observed in the patients with IgG4-RD over a mean followup period of 5.95 ± 4.48 years. The overall SIR of malignancies was 2.01 (95% CI 1.34-2.69). The SIR of patients who exhibited a tumor within 1 year after IgG4-RD diagnosis was 3.53 (95% CI 1.23-5.83), while that of subjects forming a malignancy in subsequent years was 1.48 (95% CI 0.99-1.98). The cumulative rate of malignancy development was significantly higher in patients with IgG4-RD within 12 years after diagnosis than in the Japanese general population. Comparable results were obtained for an autoimmune pancreatitis subgroup. The serum concentrations of several disease activity markers at diagnosis were significantly higher in patients with malignancies than in those without. CONCLUSION: We identified a close association between IgG4-RD and malignancy formation within 12 years after diagnosis, particularly during the first year. An active IgG4-RD state is presumed to be a strong risk factor for malignancy development.

A case of acquired hemophilia A diagnosed after percutaneous endoscopic gastrostomy.

A 65-year-old male with no personal or familial history of bleeding disorders underwent percutaneous endoscopic gastrostomy (PEG) for neurogenic dysphagia due to subarachnoid hemorrhage. On postoperative day 6, continuous oozing of venous blood was observed at the stoma. Prothrombin time was within normal range, but activated partial thromboplastin time was prolonged. Cross-mixing test results indicated the existence of an inhibitor, and laboratory findings revealed decreased factor VIII activity and high levels of factor VIII inhibitor. The patient was diagnosed as having acquired hemophilia A, for which steroid monotherapy was effective. Acquired hemophilia A is a rare but potentially fatal disease. Clinicians should be aware of this condition in patients presenting with sudden hemorrhage after PEG or other endoscopic treatments, even in those with no apparent history of bleeding.

Investigation of susceptibility genes triggering lachrymal/salivary gland lesion complications in Japanese patients with type 1 autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to manifest in a highly active AIP disease state, and several genes are speculated to be associated with the onset of this complication. We therefore searched for candidate susceptibility genes related to lachrymal/salivary gland lesions in a genome-wide association study (GWAS) with the GeneChip Human Mapping 500k Array Set (Affymetrix, CA) that was followed by fine mapping of additional single nucleotide polymorphisms (SNPs) in strongly significant genes with TaqMan assays. Venous blood samples were obtained from 50 type 1 AIP patients with lachrymal/salivary gland lesions (A group) and 53 type 1 AIP patients without (B group). The mean values of IgG and IG4 were both significantly different (P<0.05) between the groups. SNPs that showed a significant association with the A group at the genome-wide level (P<0.0001) were identified and subsequently used in fine SNP mapping of candidate genes. In total, five SNPs had a positive association with complicated AIP (most notably rs2284932 [P=0.0000021]) and five SNPs possessed a negative association (particularly rs9371942 [P=0.00000039]). Among them, KLF7, FRMD4B, LOC101928923, and MPPED2 were further examined for complication susceptibility using additional SNPs that were not included in the GWAS. Individual genotyping of KLF7 rs2284932 revealed that the frequency of the minor C allele was significantly increased (P = 0.00062, Pc = 0.003, OR = 2.98, 95%CI = 1.58­5.65) in group A. The minor T allele of rs4473559 in FRMD4 demonstrated a significant association in the A group (P = 0.00015, OR = 3.38, 95%CI = 1.77­6.45). In the LOC101928923 gene, the frequency of the minor T allele of rs4379306 was significantly decreased in group A in both TaqMan and GWAS analyses. Lastly, the minor C allele of MPPED2 rs514644 carried a significantly increased risk of complications [corrected].These four genes may be linked with the onset of lachrymal/salivary gland lesions in type 1 AIP patients and require further study.

Extracorporeal shock wave lithotripsy treatment of pancreatic stones complicated with advanced stage autoimmune pancreatitis.

BACKGROUND: Although most patients with autoimmune pancreatitis (AIP) respond favorably to prednisolone therapy, some individuals who later suffer from pancreatic calculi may require additional extracorporeal shock wave lithotripsy (ESWL) treatment. This study compares the efficacy of ESWL for calculi in AIP with that in ordinary chronic pancreatitis (CP) and proposes a new treatment approach for pancreatic duct stones occurring in AIP. METHODS: We examined the clinical records of 8 patients with chronic stage AIP and 92 patients with ordinary CP who received ESWL for pancreatic calculi. RESULTS: The AIP group was significantly older than the CP group (69.0 vs. 56.5 years, P = 0.018). With regard to the indications for ESWL, chronic pain was significantly less frequent in the chronic stage AIP group (0% vs. 45.7%, P = 0.001), whereas preservation of pancreatic function was significantly more frequent (75% vs. 19.6%, P = 0.001). Compared with the CP group, the AIP group tended to exhibit pancreatic duct stenosis proximal to pancreatic calculi and had a lower rate of complete extraction of stones from the main pancreatic duct. Histopathological analysis of a patient with chronic stage AIP revealed widely distributed nodular pancreatitis, which was characteristic of ordinary CP, along with isolated areas of lymphoplasmacytic sclerosing pancreatitis. CONCLUSIONS: Different approaches are needed for the treatment of pancreatic calculi in chronic stage AIP and ordinary CP. Specifically, it appears that intensive ESWL therapy can be avoided or delayed in AIP if the patient displays: (1) advanced age, (2) little or no chronic pain or pancreatitis, and (3) pancreatic duct stenosis proximal to pancreatic stones. In such cases, the benefit of ESWL treatment may be outweighed by the risks involved in this procedure.

Biliary tract variations of the left liver with special reference to the left medial sectional bile duct in 500 patients.

BACKGROUND: Among the intrahepatic bile ducts, the biliary system of the left medial sectional bile duct (B4) is known to have relatively complex patterns. METHODS: The records of 500 patients who had been diagnosed as having hepato-pancreatico-biliary disease were retrospectively studied for anatomical biliary variations of the left liver with special reference to the drainage system of B4 using magnetic resonance images. RESULTS: The left hepatic duct was present in 494 patients (98.8%), whereas it was lacking in 6 patients (1.2%), and these patients exhibited the following B4 confluence patterns: B4 drained into the common hepatic duct in 2 patients (.4%), the right anterior sectional bile duct in 3 patients (.6%), and the right posterior sectional bile duct in 1 patient (.2%). The left hepatic duct was absent more frequently in patients with portal venous variations than in patients with a common branching pattern (8.2% vs .4%, P = .0011). CONCLUSION: The presently reported data are useful for obtaining a better understanding of the surgical anatomy of the biliary system of the left liver.

Insulin-Like Growth Factor II mRNA-Binding Protein 3 (IMP3) as a Useful Immunohistochemical Marker for the Diagnosis of Adenocarcinoma of Small Intestine.

The biological characteristics and roles of insulin-like growth factor II mRNA-binding protein 3 protein (IMP3) expression in small-intestinal adenocarcinoma were investigated. The value of IMP3 immunostaining in the diagnosis of small-intestinal epithelial lesions was also evaluated. Immunohistochemical expression of IMP3 in normal small-intestinal mucosa adjacent to adenoma and adenocarcinoma lesions, and inflamed duodenal and ileal mucosa was analyzed. Samples assessed were: duodenal ulcer (n=6), Crohn's disease (n=5), low-grade small-intestinal adenoma (n=10), high-grade small-intestinal adenoma (n=13), small-intestinal adenocarcinoma (n=23), lymph node metastases (LNM; n=7), and preoperative biopsies of small-intestinal adenocarcinoma (n=6). Immunohistochemical expression of Ki-67 and p53 was also analyzed in adenoma and adenocarcinoma samples. IMP3 was not expressed in normal epithelium, but weakly expressed in reparative epithelium. Meanwhile, increased IMP3 expression was associated with a higher degree of dysplasia in adenomas, higher T classification, LNM, Ki-67 positivity, histological differentiation, and lower 5-year disease-free survival, but not p53 expression in adenocarcinoma. IMP3 expression appears to be a late event in the small-intestinal carcinogenesis. Assessing the IMP3 staining pattern can be useful in the diagnosis of small-intestinal epithelial lesions when used in conjunction with other histological criteria.

Hepatic infarction complicated with acute pancreatitis precisely diagnosed with gadoxetate disodium-enhanced magnetic resonance imaging.

Pancreatitis may induce a spectrum of venous and arterial vascular complications. However, hepatic infarction complicated with acute pancreatitis seldom occurs because of the unique vascular configuration of the liver. We herein describe an extremely rare and unique case in which simultaneous portal vein and hepatic vein thrombosis were present. We precisely assessed both hepatic hemodynamics and hepatocellular function using sequential multidetector computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging, which may provide useful information on the pathophysiological state and diagnosis of hepatic infarction.

Eosinophilic gastroenteritis complicated with Helicobacter pylori infection unresponsive to eradication therapy.

An adolescent girl presented with inappetence. Upper gastrointestinal endoscopy showed rough and cracked mucosa at the gastric antrum with a scarred duodenal ulcer, and a biopsy sample demonstrated abundant eosinophils. We therefore diagnosed the patient as having eosinophilic gastroenteritis. Eradication therapy for Helicobacter pylori (H. pylori) did not improve her symptoms; however, proton pump inhibitor therapy was effective in resolving her chief complaints. There are several reports of eosinophilic gastroenteritis complicated with H. pylori infection in which the association between eradication therapy and the patient's symptoms is unclear. In the present case, the patient's symptoms did not improve with eradication therapy, and there appeared to be no relationship between the two.