Intravenous injection of tumor extracellular vesicles suppresses tumor growth by reducing the regulatory T cell phenotype.

BACKGROUND: Colorectal cancer is a disease of unmet medical need. Although extracellular vesicles (EVs) have been implicated in anti-tumor responses, discrepancies were observed among studies. We analyzed the role of tumor-derived EVs (TEVs) in tumor progression in vivo by focusing on regulatory T (Treg) cells, which play essential roles in tumor development and progression. METHODS: A mouse model of colorectal cancer lung metastasis was generated using BALB/c mice by tail vein injection of the BALB/c colon adenocarcinoma cell line Colon-26. TEVs derived from Colon-26 and BALB/c lung squamous cell carcinoma ASB-XIV were retrieved from the culture media supernatants. A TEV equivalent to 10 µg protein was injected every other day for 2 weeks. RESULTS: Histology and immunohistochemistry studies revealed that lung tumors reduced in the Colon-26-EV group when compared to the phosphate-buffered saline (PBS) group. The population of CD4 + FoxP3 + cells in the lung was upregulated in the PBS group mice when compared to the healthy mice (P < 0.001), but was significantly downregulated in the Colon-26-EV group mice when compared to the PBS group mice (P < 0.01). Programmed cell death protein 1, glucocorticoid-induced TNFR-related protein, and CD69 expression in lung Treg cells were markedly upregulated in the PBS group when compared to the healthy mice, but downregulated in the Colon-26-EV group when compared to the PBS group. The changes in expression were dose-dependent for Colon-26-EVs. ASB-EVs also led to significantly downregulated Treg cell expression, although non-cancer line 3T3-derived EVs did not. CONCLUSION: Our study suggests that TEVs possess components for tumor suppression.

A Retrospective Study Investigating the Safety and Efficacy of Nanoliposomal Irinotecan in Elderly Patients with Unresectable Pancreatic Cancer.

Although nanoliposomal irinotecan combined with 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) has been used to treat first-line resistant unresectable pancreatic cancer, the efficacy and safety data among the elderly remain limited. We retrospectively analyzed clinical outcomes among elderly patients. Patients treated with nal-IRI+5-FU/LV were assigned to the elderly (≥75 years) and non-elderly (<75 years) groups. Herein, 85 patients received nal-IRI+5-FU/LV, with 32 assigned to the elderly group. Patient characteristics in the elderly and non-elderly groups were as follows: age: 78.5 (75-88)/71 (48-74), male: 17/32 (53%/60%), performance status (ECOG) 0:9/20 (28%/38%), nal-IRI+5-FU/LV in second line: 23/24 (72%/45%), respectively. A significantly high number of elderly patients exhibited aggravated kidney and hepatic functions. Median overall survival (OS) and progression-free survival (PFS) in the elderly group vs. non-elderly group were 9.4 months vs. 9.9 months (hazard ratio (HR) 1.51, 95% confidence interval (CI) 0.85-2.67, p = 0.16) and 3.4 months vs. 3.7 months (HR 1.41, 95% CI 0.86-2.32, p = 0.17). Both groups exhibited a similar incidence of efficacy and adverse events. There were no significant differences in OS and PFS between groups. We analyzed the C-reactive protein/albumin ratio (CAR) and neutrophil/lymphocyte ratio (NLR) as indicators that could determine eligibility for nal-IRI+5-FU/LV. The median CAR and NLR scores in the ineligible group were 1.17 and 4.23 (p < 0.001 and p = 0.018, respectively). Elderly patients with worse CAR and NLR score could be deemed ineligible for nal-IRI+5-FU/LV.

Primary Gastric Rhabdomyosarcoma.

Primary gastric rhabdomyosarcoma is extremely rare. An 87-year-old man visited our clinic with a chief complaint of abdominal pain. Computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT revealed a massive tumor originating from the muscularis propria of the stomach along with splenic vein tumor thrombosis. We diagnosed the patient with primary gastric rhabdomyosarcoma by an endoscopic ultrasound-guided fine-needle aspiration/biopsy.

Impact of neoadjuvant therapy on gut microbiome in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: /Objectives: Effects of chemotherapy on gut microbiota have been reported in various carcinomas. The current study aimed to evaluate the changes in the gut microbiota before and after neoadjuvant chemotherapy (NAC) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and understand their clinical implications. METHODS: Twenty patients diagnosed with R/BR-PDAC were included in this study. Stool samples were collected at two points, before and after NAC, for microbiota analysis using 16S ribosomal RNA (16S rRNA) gene sequences. RESULTS: Of the 20 patients, 18 (90%) were treated with gemcitabine plus S-1 as NAC, and the remaining patients received gemcitabine plus nab-paclitaxel and a fluorouracil, leucovorin, irinotecan, and oxaliplatin combination. No significant differences were observed in the α- and ß-diversity before and after NAC. Bacterial diversity was not associated with Evans classification (histological grade of tumor destruction by NAC) or postoperative complications. The relative abundance of Actinobacteria phylum after NAC was significantly lower than that before NAC (P = 0.02). At the genus level, the relative abundance of Bifidobacterium before NAC in patients with Evans grade 2 disease was significantly higher than that in patients with Evans grade 1 disease (P = 0.03). Patients with Evans grade 2 lost significantly more Bifidobacterium than patients with Evans grade 1 (P = 0.01). CONCLUSIONS: The diversity of gut microbiota was neither decreased by NAC for R/BR-PDAC nor associated with postoperative complications. Lower incidence of Bifidobacterium genus before NAC may be associated with a lower pathological response to NAC.

Long-term Outcomes after Steroid Pulse Therapy in Patients with Type 1 Autoimmune Pancreatitis.

Objective Steroid pulse therapy is a regimen involving the intravenous administration of supra-pharmacological doses of corticosteroids in the short term. It is used to treat various inflammatory and autoimmune conditions. However, the strengths and limitations of steroid pulse therapy for induction of remission in type 1 autoimmune pancreatitis (AIP) are unknown. Methods Depending on the steroid therapy regimen administered, the 104 patients with type 1 AIP included in this retrospective study were divided into three groups: conventional oral prednisolone (PSL) regimen (PSL group), intravenous methylprednisolone (IVMP) pulse followed by oral PSL regimen (Pulse+PSL group), and IVMP pulse-alone regimen (Pulse-alone group). We then examined the relapse rate and adverse events among the three groups. Results The Kaplan-Meier estimates of the relapse rate at 36 months after steroid therapy were 13.6% in the PSL group, 13.3% in the Pulse+PSL group, and 46.2% in the Pulse-alone group. The log-rank test revealed that the relapse-free survival in the Pulse-alone group was significantly shorter than that in the PSL (p=0.024) and Pulse+PSL groups (p=0.014). The exacerbation of glucose tolerance after steroid therapy was less frequently observed in the Pulse-alone group (0%) than in the PSL group (17%, p=0.050) and Pulse+PSL groups (26%, p=0.011). Conclusion Although treatment with IVMP pulse alone resulted in unsatisfactory relapse prevention outcomes compared with conventional steroid therapy, the IVMP pulse-alone regimen might be an alternative treatment strategy for type 1 AIP from the perspective of avoiding adverse events from steroids.

A case of type 2 autoimmune pancreatitis with spontaneous remission.

A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.

Efficacy and safety of endoscopic stent placement for afferent loop obstruction using a short double-balloon endoscopy.

Background: Afferent loop obstruction (ALO) is a rare mechanical complication that occurs after gastrojejunostomy. Recently the use of double-balloon endoscopy (DBE) can be useful for benign and malignant ALO. Methods: We retrospectively identified 22 patients who underwent DBE for ALO from January 2009 to December 2020. We evaluated the efficacy and safety of short DBE treatment for ALO. Results: Short DBE was able to reach an obstructive site in the afferent limb in all patients (100%) and was able to reach the blind end in 14 patients (64%). The technical success rate was 100%, and the clinical success rate was 95%. Procedure-related adverse events occurred in two patients (9%). In the case of benign ALO, three of nine patients showed improvement in ALO with single stent placement. Two of nine patients improved after the replacement of the plastic stent (PS) two or three times. Four of nine patients continued with the replacement of PS. In the case of malignant ALO, the metallic stent was placed in 10 patients, and eight patients with metallic stents did not experience stent occlusion until they died. Reintervention was attempted in six patients (27%) with benign ALO but was not attempted in malignant ALO. Conclusions: Treatments for ALO using the short DBE was effective and relatively safe because the technical and clinical success rates were very high and there were relatively low complications. Consequently, short DBE could be the first-choice treatment for both benign and malignant ALO.

Prophylaxis of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Using Temporary Pancreatic Stents Versus Rectal Nonsteroidal Anti-inflammatory Drugs: A Randomized Controlled Trial.

OBJECTIVES: Both pancreatic stenting and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. The aim of the study was to compare post-ERCP pancreatitis (PEP) prophylaxis using pancreatic stents and/or rectal NSAIDs prospectively. METHODS: A total of 321 patients undergoing ERCP were studied. Each patient was randomly allocated to receive pancreatic stent placement (PS), 50 mg of rectal diclofenac (NSAID), or both (PS + NSAID) for PEP prophylaxis. The primary outcome was the occurrence rate of PEP, and secondary outcomes included the severity of PEP and serum pancreatic amylase and lipase levels on the day after ERCP. RESULTS: Five patients (PS: 2/101, NSAID: 1/106, PS + NSAID: 2/102) developed PEP, and the overall occurrence rate of PEP was 1.6% (5/309). The occurrence rates of PEP in the PS, NSAID, and PS + NSAID groups were statistically equivalent with an equivalent margin of 10%. The severity of PEP was mild in all 5 patients. Median serum pancreatic amylase and lipase levels in the NSAID group were significantly lower than those in the PS and PS + NSAID groups. CONCLUSIONS: Rectal administration of 50 mg of diclofenac may become a first-line therapy for PEP prophylaxis in our country.

Analysis of the initial dose and reduction rate of corticosteroid for ulcerative colitis in clinical practice.

Background and Aim: Trends in steroid use and the effects of the initial dose, duration of use, and tapering schedule on clinical efficacy were assessed in Japanese patients with ulcerative colitis (UC) undergoing steroid treatment. Methods: We enrolled 191 cases with UC who underwent steroid treatment between 2006 and 2020. We assessed the difference in clinical remission rates in cases with different initial doses of steroid. Clinical factors for clinical remission at week 4 and discontinuation of corticosteroid within 12 weeks were also assessed. Results: Clinical remission and response at week 4 were obtained in 107 (56.0%) and 58 cases (30.4%), respectively. In hospitalized patients, male sex (odds ratio [OR], 0.373; 95% confidence interval [CI], 0.146-0.956) and younger age (OR, 0.974; 95% CI, 0.951-0.998) were associated with clinical remission at week 4. Partial Mayo score (OR, 0.643; 95% CI, 0.451-0.918) and initial steroid dose of ≥30 mg (OR, 3.278; 95% CI, 1.274-8.435) were associated with clinical remission at week 4 in outpatients. Clinical remission at week 4 (OR, 0.300; (95% CI, 0.126-0.718)) and the steroid dose reduction rate at week 4 (OR, 0.092; 95% CI, 0.036-0.234) were associated with treatment discontinuation within 12 weeks. The proportion of patients in whom corticosteroids were discontinued at week 12 was significantly higher (P = 0.006) in 2016-2020 (28/52; 53.8%) than in 2006-2010 (15/54; 27.8%). Conclusion: The steroid reduction rate at week 4 may be critical for discontinuation within 12 weeks. Withdrawal of corticosteroids has been becoming more appropriate in the last 5 years than before.

Repeated Stimulation of Toll-Like Receptor 2 and Dectin-1 Induces Chronic Pancreatitis in Mice Through the Participation of Acquired Immunity.

BACKGROUND: Stimulation of Toll-like receptor 3 (TLR3) induces autoimmune-mediated pancreatitis in susceptible mice, whereas stimulation of TLR4 causes nonautoimmune-mediated pancreatitis. However, the effects of TLR2 stimulation on the pancreas are unknown. AIMS: We investigated the role of TLR2 stimulation on pancreatic damage by repeatedly stimulating mice with TLR2 ligands. METHODS: Wild-type (WT) and interleukin 10-deficient (IL-10-knockout (KO)) mice were administered zymosan and lipoteichoic acid (LTA) intraperitoneally at various doses twice weekly for 4 weeks. Syngeneic T-cell-deficient mice, B-cell-deficient mice, recombination activating gene 2-deficient (RAG2-KO) mice and RAG2-KO mice that had been reconstituted with CD4+ or CD8+ T cells isolated from WT mice were treated with zymosan similarly. Mice were killed, the severity of pancreatitis was graded histologically, and serum cytokine levels were measured. RESULTS: Repeated administration of zymosan induced pancreatitis dose dependently in both WT and IL-10-KO mice. Administration of LTA induced pancreatitis only in IL-10-KO mice. Adoptive transfer of splenocytes obtained from IL-10-KO mice with pancreatitis did not cause pancreatitis in recipient RAG2-KO mice. Pancreatitis was scarcely observed in RAG2-KO mice and was attenuated in T-cell-deficient and B-cell-deficient mice compared with WT mice. A single administration of zymosan significantly increased the serum level of monocyte chemoattractant protein 1 (MCP-1) in WT mice. CONCLUSIONS: Repeated stimulation of TLR2 and dectin-1 induced nonautoimmune-mediated pancreatitis in mice. Participation of acquired immunity seems to play an important role in the pathogenesis of pancreatitis in association with the increase in serum MCP-1 level.

Risk factors and treatment strategy for clinical hepatico-jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy: A retrospective study.

BACKGROUNDS/PURPOSE: The purpose of this study was to identify risk factors and establish a treatment strategy for clinical hepatico-jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy. METHODS: The 443 patients who underwent PD from April 2006 to December 2015 were analyzed. Clinical characteristics were compared between patients with and without clinical HJ stenosis, and risk factors for clinical HJ stenosis were analyzed. In addition, the treatment and clinical course of patients with clinical HJ stenosis were retrospectively reviewed. RESULTS: Clinical HJ stenosis defined with intrahepatic bile duct dilatation was identified in 40 patients (9.0%). Multivariate analysis revealed that the independent risk factor for clinical HJ stenosis was the hepatic duct at surgery ≤8 mm. Endoscopic HJ stenosis was identified in 36 patients, and 31 patients were treated successfully with double balloon endoscopic retrograde cholangiography; five patients required re-anastomosis (n = 3) and percutaneous transhepatic biliary drainage (n = 2). Complete obstruction of HJ was found in five patients, and treatment with DB-ERC was successful in only one patient. CONCLUSION: The independent risk factor for clinical HJ stenosis was hepatic duct diameter ≤8 mm. Most cases of endoscopic HJ stenosis were treated successfully with DB-ERC, except in patients with complete obstruction.

Rectally Administered Low-Dose Diclofenac Has No Effect on Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Propensity Score Analysis.

OBJECTIVES: We evaluated the preventive effect of low-dose diclofenac (25-50 mg) on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) by propensity score matching analysis. METHODS: We retrospectively analyzed the data of 515 patients who underwent ERCP for the first time with or without the rectal administration of low-dose diclofenac before the procedure. For the purpose of minimization of the intrinsic selection bias, we compared the incidence rate of PEP between the diclofenac and control group after propensity score matching. RESULTS: Post-ERCP pancreatitis developed in 15 patients (2.9%). There was no significant difference in the incidence of PEP between the diclofenac (2.4%) and control group (3.3%) (P = 0.608). One hundred ninety matched pairs were generated by propensity score matching and analyzed; however, the incidence rate of PEP was the same in both groups (2.1%, P = 1.000). In the subgroup analysis using data of patients with high-risk factors for developing PEP, the incidence rate of PEP was comparable between the diclofenac (3.8%) and control groups (4.0%) (P = 0.917). CONCLUSIONS: In our propensity score analysis, rectal administration of low-dose diclofenac was not shown to be useful in preventing PEP.

Development of Severe Acute Pancreatitis Following Uncovered Metallic Stent Placement: A Rare Case Report.

Self-expandable metallic stents (SEMSs) are widely used for malignant biliary stricture (MBS). Acute pancreatitis is an early complication following SEMS placement. In the present case, the patient developed severe acute pancreatitis after SEMS placement for MBS because of metastatic lymph nodes. Endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy and an endoscopic nasobiliary drainage tube placement were performed. After seven days, an uncovered SEMS was placed; however, severe acute pancreatitis occurred, and the SEMS was drawn out emergently. In SEMS placement for patients with MBS caused by non-pancreatic cancer, SEMS should be selected carefully while considering each patient's case.

Recent advances of endoscopic retrograde cholangiopancreatography using balloon assisted endoscopy for pancreaticobiliary diseases in patients with surgically altered anatomy: Therapeutic strategy and management of difficult cases.

Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic modality established for diagnosis and treatment of pancreaticobiliary diseases. However ERCP in patients with surgically altered anatomy (SAA) has been difficult, and more invasive therapies have been primarily selected. The development of balloon assisted endoscopes (BAEs) innovatively facilitated ERCP in such patients. Recent advances of BAEs and other devices greatly contributed to increasing success of ERCP using BAEs (BAE-ERCP). Furthermore, interventions using Endoscopic Ultrasound (EUS-intervention) have been reported to be useful for pancreaticobiliary diseases in patients with SAA, which provide more options for endoscopic therapies and are also expected as a rescue therapy for difficult cases of BAE-ERCP. In order to thoroughly complete endoscopic treatment for pancreaticobiliary diseases with SAA, it is important to standardize the BAE-ERCP procedures based on the features of respective endoscopes and to establish a strategy for endoscopic treatment which includes analysis of BAE-ERCP difficult cases and selection of cases for rescue therapy. In addition, it is essential to be acquainted with the characteristics of possible adverse events of the procedure and to be able to deal with them for safe accomplishment of endoscopic treatment.

Usefulness of half-covered metallic stent placement in preventing acute cholecystitis complication in pancreatic cancer-induced distal biliary stricture.

BACKGROUND AND AIM: A self-expandable metallic stent (SEMS) is commonly used for biliary stricture caused by pancreatic cancer. Covered SEMS may obstruct the cystic duct, causing acute cholecystitis. This study aimed to determine the outcomes of using a half-covered SEMS with an offset covered portion for preventing cystic duct obstruction. METHODS: Among 80 patients with half-covered SEMS placement for the treatment of pancreatic cancer-induced distal biliary stricture, 74 were followed up. The half-covered SEMS has a total length of 6 or 7 cm, and the offset covered part was 0.5-4.5 or 0.5-5.5 cm, respectively. Intraductal ultrasonography (IDUS) and endoscopic nasobiliary drainage (ENBD) were performed during the initial endoscopic retrograde cholangiopancreatography (ERCP). IDUS findings and ENBD tube cholangiogram confirmed the cystic duct confluence. SEMS placement was performed on the second ERCP or several weeks after the initial tube stent placement. RESULTS: Half-covered SEMS placement was successful in all patients. However, four (5.4%) patients exhibited early complications, including acute cholecystitis in one patient and stent displacement in another. Over 30 days, cholangitis, tumor growth, and stent displacement occurred in nine (11.3%), five (6.3%), and two (2.5%) patients, respectively. The median stent patency was 71.1 weeks, and the median overall survival in patients with and without chemotherapy was 31.8 and 12.2 weeks, respectively. CONCLUSIONS: With confirmation of the cystic duct confluence, half-covered SEMS placement may become a treatment option for distal biliary stricture caused by pancreatic cancer to prevent acute cholecystitis. Half-covered SEMS patency was comparable with that of covered SEMS.

Evaluation of complications after endoscopic retrograde cholangiopancreatography using a short type double balloon endoscope in patients with altered gastrointestinal anatomy: a single-center retrospective study of 1,576 procedures.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) using balloon-assisted endoscope such as double-balloon endoscope is even effective for patients with surgically altered anatomy. Yet comprehensive studies on complications of ERCP using balloon-assisted endoscope have not been made. We analyzed the characteristics and the causes of complications of ERCP using double-balloon endoscope (DB-ERCP) procedures and aimed to suggest effective managements. METHODS: A total of 1576 procedures of DB-ERCP in 714 patients with surgically altered gastrointestinal anatomy in our hospital were evaluated retrospectively using a statistic analysis. RESULTS: The overall complication occurrence rate was 5.8%. By type of complications are perforation 3.2%, mucosal laceration 0.5%, hemorrhage 1.0%, pancreatitis 0.6%, respiratory disorder 0.4%, and others 0.2%. By type of surgical reconstruction methods were Roux-en-Y reconstruction with choledocho-jejunal anastomosis 4.2%, Roux-en-Y reconstruction without choledocho-jejunal anastomosis 6.7%, pancreaticoduodenectomy 4.5%, pylorus preserving pancreaticoduodenectomy 4.2%, Billroth II gastrectomy (B-II) 11.6%, and other reconstruction method (others) 7.4%. The contributing factors calculated by a multivariate analysis were B-II (odds ratio: 1.864, 95% confidence interval: 1.001-3.471, P = 0.050) and the presence of naïve papilla (odds ratio: 3.268, 95% confidence interval: 1.426-7.490, P = 0.005). CONCLUSIONS: DB-ERCP is a safe method with a total complication rate of 5.8% that could be considered within an acceptable range. The most common complication was the injury of the digestive tract such as perforation. Affecting risk factors for complications were B-II and the presence of naïve papilla. DB-ERCP procedures should be performed carefully of these factors.

Clinical implications of elevated serum interleukin-6 in IgG4-related disease.

INTRODUCTION: Some patients with IgG4-related disease (IgG4-RD) exhibit elevated serum interleukin (IL)-6 with excessive inflammatory reactions or with repeating relapse. To date few reports pertaining to clinical implications of elevated serum IL-6 in IgG4-RD patients have been published. The aims of the current retrospective study were to investigate the clinical implications of elevated serum IL-6 in IgG4-RD patients, and to examine whether IL-6 can predict the activity and/or relapse of the disease. MATERIALS AND METHODS: We examined the clinical picture at the onset of 43 patients who were diagnosed with IgG4-RD in our hospital and were able to measure serum IL-6 before steroid treatment. RESULTS: The median level of serum IL-6 was 2.2 pg/mL. There was a significant correlation between IL-6 and C-reactive protein (CRP) level (r = 0.397, p = 0.008), hemoglobin level (r = -0.390, p = 0.010) and albumin level (r = -0.556, p < 0.001). When 43 patients were divided into two groups by using a cut-off IL-6 of 4 pg/mL, the high IL-6 group showed higher age, lower albumin, higher CRP and higher aspartate aminotransferase (AST) (age p = 0.014, albumin p = 0.006, CRP p <0.001, AST p = 0.009). Hepatic swelling and splenomegaly were significantly more prevalent in the high IL-6 group than it was in the low IL-6 group (liver p < 0.001, spleen p = 0.020). Biliary tract involvement tended to admit more in the high IL-6 group (p = 0.060). CONCLUSION: Serum IL-6 level at the onset of IgG4-RD may be significantly correlated with clinical inflammatory parameters and it may also be associated with involvement of the bile duct, liver, and spleen.

Diffuse Pancreatic Cancer Mimicking Autoimmune Pancreatitis.

The characteristic finding of sausage-shaped pancreas or capsule-like rim facilitates the diagnosis of autoimmune pancreatitis. We herein report a case of a 67-year-old man showing a sausage-shaped, enlarged pancreas with a capsule-like rim on computed tomography. Furthermore, endoscopic retrograde cholangiopancreatography demonstrated diffuse narrowing of the main pancreatic duct, in addition to stenosis of the lower bile duct. Finally, we were able to diagnose pancreatic cancer in this patient by an endoscopic ultrasound-guided fine-needle aspiration biopsy following peroral cholangioscopy and bile cytology. This report emphasizes the significance of pathological confirmation before starting treatment, even in cases with diffuse pancreatic enlargement.

Inhibition of the dephosphorylation of eukaryotic initiation factor 2α ameliorates murine experimental pancreatitis.

BACKGROUND: Endoplasmic reticulum (ER) stress in the pancreas is closely associated with the development of acute pancreatitis. However, the role of the protein kinase RNA-like ER kinase (PERK) in this disease is not fully understood. We investigated whether an inhibitor of the dephosphorylation of eukaryotic initiation factor 2α, salubrinal, could improve murine experimental pancreatitis through the amelioration of ER stress. METHODS: Acute pancreatitis was induced by the intraperitoneal administration of cerulein (50 µg/kg) six times at 1-h intervals followed by lipopolysaccharide (10 mg/kg). Salubrinal was administered intraperitoneally immediately after lipopolysaccharide injection and 3 h later. Mice were sacrificed 24 h after the first injection of cerulein, and serum amylase and proinflammatory cytokines were measured. The severity of pancreatitis was evaluated histologically using a scoring system. The expression levels of ER stress-related proteins were evaluated by Western blotting. RESULTS: The administration of salubrinal significantly attenuated the increase in serum amylase levels and improved histologically assessed pancreatitis. The serum levels of proinflammatory cytokines were significantly suppressed in salubrinal-treated mice, as was the expression of glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, and cleaved caspase-3. CONCLUSIONS: The amelioration of ER stress through augmentation of the PERK-signaling pathway may be a therapeutic target for the treatment of acute pancreatitis.