Akira Horiuchi

High Serum IgG4 Concentrations in Patients with Sclerosing Pancreatitis

BACKGROUND Sclerosing pancreatitis is a unique form of pancreatitis that is characterized by irregular narrowing of the main pancreatic duct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and that responds to glucocorticoid treatment. Preliminary studies suggested that serum IgG4 concentrations are elevated in this disease but not in other diseases of the pancreas or biliary tract. METHODS We measured serum IgG4 concentrations using single radial immunodiffusion and an enzyme-linked immunosorbent assay in 20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or Sjögrens syndrome. Serum concentrations of immune complexes and the IgG4 subclass of immune complexes were determined by means of an enzyme-linked immunosorbent assay with monoclonal rheumatoid factor. RESULTS The median serum IgG4 concentration in the patients with sclerosing pancreatitis was 663 mg per deciliter (5th and 95th percentiles, 136 and 1150), as compared with 51 mg per deciliter (5th and 95th percentiles, 15 and 128) in normal subjects (P<0.001). The serum IgG4 concentrations in the other groups of patients were similar to those in the normal subjects. In patients with sclerosing pancreatitis, serum concentrations of immune complexes and the IgG4 subclass of immune complexes were significantly higher before glucocorticoid therapy than after four weeks of such therapy. Glucocorticoid therapy induced clinical remissions and significantly decreased serum concentrations of IgG4, immune complexes, and the IgG4 subclass of immune complexes. CONCLUSIONS Patients with sclerosing pancreatitis have high serum IgG4 concentrations, providing a useful means of distinguishing this disorder from other diseases of the pancreas or biliary tract.

Endoscopist-Directed Administration of Propofol: A Worldwide Safety Experience

BACKGROUND & AIMS Endoscopist-directed propofol sedation (EDP) remains controversial. We sought to update the safety experience of EDP and estimate the cost of using anesthesia specialists for endoscopic sedation. METHODS We reviewed all published work using EDP. We contacted all endoscopists performing EDP for endoscopy that we were aware of to obtain their safety experience. These complications were available in all patients: endotracheal intubations, permanent neurologic injuries, and death. RESULTS A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified. Endotracheal intubations, permanent neurologic injuries, and deaths were 11, 0, and 4, respectively. Deaths occurred in 2 patients with pancreatic cancer, a severely handicapped patient with mental retardation, and a patient with severe cardiomyopathy. The overall number of cases requiring mask ventilation was 489 (0.1%) of 569,220 cases with data available. For sites specifying mask ventilation risk by procedure type, 185 (0.1%) of 185,245 patients and 20 (0.01%) of 142,863 patients required mask ventilation during their esophagogastroduodenoscopy or colonoscopy, respectively (P < .001). The estimated cost per life-year saved to substitute anesthesia specialists in these cases, assuming they would have prevented all deaths, was

Highly Purified Eicosapentaenoic Acid Treatment Improves Nonalcoholic Steatohepatitis

5.3 million. CONCLUSIONS EDP thus far has a lower mortality rate than that in published data on endoscopist-delivered benzodiazepines and opioids and a comparable rate to that in published data on general anesthesia by anesthesiologists. In the cases described here, use of anesthesia specialists to deliver propofol would have had high costs relative to any potential benefit.

Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: A case report and review of the Japanese literature

Recent studies have demonstrated that n-3 polyunsaturated fatty acids ameliorate nonalcoholic fatty liver disease. Although eicosapentaenoic acid (EPA), one of the major components of n-3 polyunsaturated fatty acids, is widely used as an antilipidemic agent, its single efficacy for nonalcoholic steatohepatitis (NASH) remains unclear. As such, we aimed to evaluate the efficacy and safety of EPA on 23 biopsy-proven NASH patients in a pilot trial. Highly purified EPA (2700 mg/d) was administered for 12 months and efficacy was assessed by biochemical parameters and liver histology. All patients completed the treatment with no adverse events, indicating acceptable tolerance to the treatment. After 12 months, serum alanine aminotransferase levels were significantly improved (from 79±36 to 50±20 U/L), and serum free fatty acids, plasma soluble tumor necrosis factor receptor 1 and 2 levels, and serum ferritin and thioredoxin levels, which may reflect hepatic oxidative stress, were significantly decreased. Body weight, blood glucose, insulin, and adiponectin concentrations remained unchanged. Seven of the 23 patients consented to undergo posttreatment liver biopsy, which showed improvement of hepatic steatosis and fibrosis, hepatocyte ballooning, and lobular inflammation in 6 patients. In conclusion, EPA treatment seems to be safe and efficacious for patients with NASH, largely due to its anti-inflammatory and antioxidative properties. To confirm these results, appropriately powered, controlled trials are needed.

Prospective randomized comparison of cold snare polypectomy and conventional polypectomy for small colorectal polyps.

We report a case demonstrating the progressive narrowing of the pancreatic duct, which is presumed to be characteristic of autoimmune pancreatitis, and we review the 37 cases of chronic pancreatitis in which autoimmunity was suggested as an etiological factor in the Japanese literature. A 55-year-old man presented with abdominal discomfort, jaundice, and diffuse swelling of the pancreas on ultrasonography. Serial endoscopic retrograde pancreatography demonstrated the progression of an irregular narrowing of the main pancreatic duct forming diffusely over the course of 2 months. Because the patient had hyperglobulinemia and tested positive for autoantibodies, he was diagnosed as a case of autoimmune chronic pancreatitis. Steroid therapy was carried out with excellent success.

Biliary stenting in the management of large or multiple common bile duct stones

Background and Aim: The ideal method to remove small colorectal polyps is unknown. We compared removal by colon snare transection without electrocautery (cold snare polypectomy) with conventional electrocautery snare polypectomy (hot polypectomy) in terms of procedure duration, difficulty in retrieving polyps, bleeding, and post-polypectomy symptoms. Methods: Patients with colorectal polyps up to 8 mm in diameter were randomized to polypectomy by cold snare technique (cold group) or conventional polypectomy (conventional group). The principal outcome measures were abdominal symptoms within 2 weeks after polypectomy. Secondary outcome measures were the rates of retrieval of colorectal polyps and bleeding. Results: Eighty patients were randomized: cold group, n = 40 (101 polyps) and conventional group, n = 40 (104 polyps). The patients’ demographic characteristics and the number and size of polyps removed were similar between the two techniques. Procedure time was significantly shorter with cold polypectomy vs. conventional polypectomy (18 vs. 25 min, p < 0.0001). Complete polyp retrieval rates were identical [96% (97/101) vs. 96% (100/104)]. No bleeding requiring hemostasis occurred in either group. Abdominal symptoms shortly after polypectomy were more common with conventional polypectomy (i.e. 20%; 8/40) than with cold polypectomy (i.e. 2.5%; 1/40; p = 0.029). Conclusion: Cold polypectomy was superior to conventional polypectomy in terms of procedure time and post-polypectomy abdominal symptoms. The two methods were otherwise essentially identical in terms of bleeding risk and complete polyp retrieval. Cold polypectomy is therefore the preferred method for removal of small colorectal polyps.

Nasopharyngeal Decolonization of Methicillin-Resistant Staphylococcus aureus Can Reduce PEG Peristomal Wound Infection

BACKGROUND Endoscopic biliary stenting with a plastic stent is often performed to prevent impaction of common bile duct (CBD) stones. The therapeutic effect of a plastic stent placement in terms of reduction in stone size and number has not been established. OBJECTIVE The aim of this study was to study the effect of biliary stenting as therapy for CBD stones. DESIGN Retrospective study. SETTING Municipal hospital outpatients. INTERVENTIONS Patients with large (> or = 20 mm) and/or multiple (> or = 3) stones had placement of a 7F double-pigtail plastic stent without stone extraction at the initial ERCP. Approximately 2 months later, stone removal was attempted. The number and size of CBD stones before and after stent placement, stone clearance, complications, and 180-day mortality were evaluated. RESULTS Forty patients were studied. Stent placement averaged 65 days (range, 50-82 days). The median number (interquartile range) of stones per patient fell after stent placement (4.0 [3.0] before vs. 2.0 [1.0] after; P < .0001). Characteristically, larger stones became smaller and small stones disappeared (ie, the median stone index decreased from 4.6 [3.0] to 2.0 [1.5]; P < .0001). Stone clearance at the second ERCP was achieved in 37 out of 40 patients (93%). Complications included cholangitis (13%) and pancreatitis (5%) after the second ERCP. No 180-day mortality occurred. LIMITATIONS A retrospective, single-center study. CONCLUSIONS Stent placement for 2 months was associated with large and/or multiple CBD stones becoming smaller and/or disappearing without any complications. Stenting followed by a wait period may assist in difficult CBD stone removal.

Down-regulation of SREBP-1c is associated with the development of burned-out NASH.

OBJECTIVES:The aim of this study is to determine whether nasopharyngeal decolonization of methicillin-resistant Staphylococcus aureus (MRSA) can reduce peristomal wound infection shortly after percutaneous endoscopic gastrostomy (PEG) placement.METHODS:Of the 84 hospitalized patients referred for PEG, 72 were enrolled in a one-third observation (Group A) and two-thirds in a randomized trial (Groups B and C). Nasopharyngeal swabs were taken from a consecutive series of patients prior to PEG insertion. Based upon these results, they were classified into three groups: Group A, MRSA-negative (n = 24), Group B, MRSA-positive, but not eradicated (n = 24), Group C, MRSA-positive and eradicated with intranasal application of mupirocin, arbekacin inhalation, and oral sulfamethoxazole/trimethoprim (n = 24). The standard PEG pull-through insertion technique was performed on all 72 patients. All patients received prophylactic and concomitant antibiotics. Infections at the peristomal site were prospectively evaluated and defined as having at least two of the following conditions: peristomal erythema, induration, and purulent discharge. Bacterial culture using purulent discharge was performed.RESULTS:There was significant difference in the peristomal infection rates among the groups: Group A, 0% (0/0); Group B, 100% (24/24); Group C, 8% (2/24) (p≤ 0.0001). In Group C, nasopharyngeal decolonization of MRSA, which was achieved by the combination of intranasal mupirocin, arbekacin inhalation, and oral sulfamethoxazole/trimethoprim in all 24 patients, significantly reduced peristomal infections. Eighteen (16 in Group B and 2 in Group C) of these 26 infected patients had cellulitis and developed purulent discharge from which MRSA was isolated.CONCLUSIONS:Nasopharyngeal decolonization of MRSA can reduce peristomal infection shortly after the pull-through PEG insertion. MRSA appears to be a major pathogen in PEG peristomal infection while prophylactic and concomitant antibiotics are being used.

Low-Dose Propofol Sedation for Diagnostic Esophagogastroduodenoscopy: Results in 10,662 Adults

BACKGROUND & AIMS It is well-known that hepatic triglycerides (TG) diminish with the progression of non-alcoholic steatohepatitis (NASH), which has been designated as burned-out NASH, but its mechanism remains unclear. We aimed to explore the changes in hepatic fatty acid (FA) and TG metabolism with disease progression. METHODS Hepatic expression of key genes in healthy individuals (n=6) and patients with simple steatosis (SS, n=10), mild NASH (fibrosis stage 1-2, n=20), and advanced NASH (fibrosis stage 3-4, n=20) were assessed by quantitative polymerase chain reaction. RESULTS Hepatic expression of genes related to FA uptake and oxidation and very-low-density lipoprotein synthesis/export did not differ among the groups. However, the mRNA levels of sterol regulatory element-binding protein (SREBP)-1c and its downstream genes FA synthase, acetyl-coenzyme A carboxylase 1, and diacylglycerol acyltransferase 1 were inversely correlated with fibrosis stage. Immunoblot analysis revealed a remarkable reduction in mature SREBP-1c levels in advanced NASH. Furthermore, hepatic expression of tumor necrosis factor-alpha increased in accordance with fibrosis progression, which was possibly related to the decrease in hepatic SREBP-1c expression. CONCLUSIONS Down-regulation of SREBP-1c and lipogenic enzymes may be associated with the development of burned-out NASH.

Eicosapentaenoic acid improves hepatic steatosis independent of PPARα activation through inhibition of SREBP-1 maturation in mice

OBJECTIVE:The use of propofol sedation during endoscopic procedures has increased in recent years. The aim of this study was to evaluate the safety and effectiveness of nurse-administered low-dose propofol sedation for diagnostic esophagogastroduodenoscopy (EGD).METHODS:We prospectively assessed the outcome and complications of low-dose bolus propofol for endoscopic sedation for diagnostic EGD. Propofol was administered by bolus injection, with a standard protocol of 40 mg for patients <70 years old, 30 mg for patients 70–89 years old, and 20 mg for patients 90 years or older. When required for adequate sedation, additional doses were given, to a maximum of 120 mg. The primary outcome measure was respiratory depression, defined as oxygen desaturation (SpO2 <90%) that continued for more than 20 s. Secondary measures included successful procedures, full recovery within 60 min of the procedure, and complications.RESULTS:All procedures were successful; 8,431 of 10,662 patients (79.1%) completed diagnostic EGD with a single bolus of propofol. Only 0.26% (28 patients) required transient supplemental oxygen supply; neither mask ventilation nor endotracheal intubation was required. Full recovery occurred in 99.9% of patients 60 min after the procedure. Men and younger patients required significantly higher doses of propofol than did the women and older patients (men vs. women, 46.5±19 vs. 42.7±15 mg, P=0.0008; age 40–49 vs. age 50–59, 51.5±16 vs. 46.3±13 mg, P<0.0001). Of the 400 patients, 368 (92%) wanted to drive home or to their offices, and all did so without incident. A total of 99% were willing to repeat the same procedure again.CONCLUSIONS:Low-dose nurse-administered propofol sedation is safe and practical for diagnostic EGD.