Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis

BACKGROUND: Autoimmune pancreatitis is a unique clinical entity proposed recently, and is sometimes associated with inflammation of other organs. AIMS: To examine the pathophysiology of the pancreas and other organs in patients with autoimmune pancreatitis. PATIENTS AND METHODS: We evaluated clinicopathological findings in six resected and one autopsied patient with autoimmune pancreatitis. The pancreas, peripancreatic tissue, bile duct, and gall bladder were examined histologically and immunohistochemically. Biopsied salivary gland and cervical lymph node of one patient were also examined. We also performed similar immunohistochemical examinations in pancreatectomy specimens from 10 patients with alcoholic chronic pancreatitis and biopsied salivary glands from five patients with Sj?gren's syndrome. RESULTS: Stenosis of the extrahepatic bile duct was detected in all patients. Histological findings were characterised by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Immunohistochemically, diffusely infiltrating cells consisted predominantly of CD4 or CD8 positive T lymphocytes and IgG4 positive plasma cells. Similar inflammatory processes also involved the peripancreatic tissue, extrahepatic bile duct, gall bladder, and salivary gland. Lymph nodes were swollen with infiltration of IgG4 positive plasma cells. None of these findings was seen in alcoholic chronic pancreatitis or Sj?gren's syndrome. CONCLUSIONS: The development of the specific inflammations in extensive organs as well as the pancreas in patients with autoimmune pancreatitis strongly suggests a close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.     

Technique to Confirm Occlusal Contact Using an Articulating Paper Holder Equipped with Tongue Depressor

This technical report describes a simple procedure for verifying occlusal contact with the use of a new device that combines the functions of a tongue depressor and an articulating paper holder. Verifying occlusal contact and/or the maxillomandibular relationship record can be expected to be simpler and easier with this device compared to the conventional holder, especially for patients with tongue hypertrophy or obesity and those treated under general anesthesia, among others.     

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis

The standard treatment for autoimmune pancreatitis (AIP) is steroid therapy, although some patients improve spontaneously. Indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, back pain, and the presence of symptomatic extrapancreatic lesions. Prior to steroid therapy, obstructive jaundice should be managed by biliary drainage, and blood glucose levels should be controlled in patients with diabetes mellitus. The recommended initial oral prednisolone dose for induction of remission is 0.6 mg/kg/day, which is administered for 2–4 weeks. The dose is then tapered by 5 mg every 1–2 weeks, based on changes in clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5–5 mg/day) over a period of 2–3 months. Cessation of steroid therapy should be based on the disease activity in each case. Termination of maintenance therapy should be planned within 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapse. Application of immunomodulatory drugs is considered for AIP patients who prove resistant to steroid therapy. The prognosis of AIP appears to be good over the short-term with steroid therapy. The long-term outcome is less clear, as there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy.     

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 I. Concept and diagnosis of autoimmune pancreatitis

Background

In response to the proposal of the international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis (AIP) and the Japanese diagnostic criteria in 2011, the 2009 Japanese consensus guidelines for managing AIP required revision.

Methods

Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Fifteen specialists for AIP extracted the specific clinical statements from 1,843 articles published between 1963 and 2012 (obtained from Pub Med and a secondary database, and developed the CQs and statements. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid.

Results

The professional committee created 13 CQs and statements for the current concept and diagnosis of AIP, 6 for extra-pancreatic lesions, 6 for differential diagnosis, and 11 for treatment.

Conclusion

After evaluation by the moderators, amendments to the Japanese consensus guidelines for AIP have been proposed for 2013.     

Safety and efficacy of metallic stent for unresectable distal malignant biliary obstruction in elderly patients

AIM To study the safety of insertion of metallic stents in elderly patients with unresectable distal malignant biliary obstruction.METHODS Of 272 patients with unresectable distal malignant biliary obstruction, 184 patients under the age of 80 were classified into Group A, and 88 subjects aged 80 years or more were classified into Group B. The safety of metallic stent insertion, metal stent patency period, and the obstruction rate were examined in each group.RESULTS In Group B, patients had a significantly worse per-formance status, high blood pressure, heart disease, cerebrovascular disease, and dementia; besides the rate of patients orally administered antiplatelet drugs or anticoagulants tended to be higher(P 0.05). Metallic stents were successfully inserted in all patients. The median patency period was 265.000 ± 26.779(1-965) d; 252.000 ± 35.998(1-618) d in Group A and 269.000 ± 47.885(1-965) d in Group B, with no significant difference between the two groups. Metallic stent obstruction occurred in 82 of the 272(30.15%) patients; in 53/184(28.80%) patients in Group A and in 29/88(32.95%) of those in Group B, showing no significant difference between the two groups. Procedural accidents due to metal stent insertion occurred in 24/272(8.8%) patients; in 17/184(9.2%) of patients in Group A and in 7/88(8.0%) of those in Group B, with no significant difference between the two groups, either.CONCLUSION These results suggested that metallic stents can be safely inserted to treat unresectable distal malignant biliary obstruction even in elderly patients aged 80 years or more.     

Clinical significance of the accessory pancreatic duct

BACKGROUND/AIMS: The accessory pancreatic duct is the smaller and less constant pancreatic duct in comparison with the main pancreatic duct. We investigated the patency of the accessory pancreatic duct and its role in pancreatic pathophysiology. METHODOLOGY: Dye-injection endoscopic retrograde pancreatography was performed in 411 patients. In patients in whom the main pancreatic duct could be selectively cannulated, contrast medium with indigo carmine was injected through the catheter. Excretion of the dye from the minor duodenal papilla was observed endoscopically. RESULTS: Patency of the accessory pancreatic duct was 43% of the 291 control cases. In the 46 patients with acute pancreatitis, 8 (17%) had a patent accessory pancreatic duct. The difference in patency between this group and the normal group was significant (p < 0.01). Especially, patency of the accessory pancreatic duct was only 8% of the 13 patients with acute biliary pancreatitis. In the patients with pancreaticobiliary maljunction, biliary carcinoma occurred in 72% of patients with a nonpatent accessory pancreatic duct, but in contrast, it occurred only in 30% of those with a patent accessory pancreatic duct. This difference was significant (p < 0.05). Lower amylase level in the bile of patients with pancreaticobiliary maljunction with a patent accessory pancreatic duct was frequently observed than those with a nonpatent accessory pancreatic duct. CONCLUSIONS: A patent accessory pancreatic duct may prevent acute pancreatitis by lowering the pressure in the main pancreatic duct. In cases of pancreaticobiliary maljunction with a patent accessory pancreatic duct, the incidence of carcinogenesis of the bile duct might be lower, as the reflux of the pancreatic juice to the bile duct might be reduced by the flow of the pancreatic juice into the duodenum through the accessory pancreatic duct.     

EUS elastography combined with the strain ratio of tissue elasticity for diagnosis of solid pancreatic masses

Background

Recently, the usefulness of endoscopic ultrasound (EUS) elastography has been reported for the diagnosis of pancreatic lesions. In the present study, we retrospectively assessed EUS elastography as a diagnostic tool by evaluating tissue elasticity distribution and elasticity semiquantification, using the strain ratio (SR) of tissue elasticity, in patients with pancreatic masses.

Methods

One hundred and nine patients who underwent EUS elastography between September 2006 and May 2009 were retrospectively evaluated. The final diagnosis was chronic pancreatitis (CP) in 20 patients [6 with non-mass-forming pancreatitis, 7 with mass-forming pancreatitis (MFP), and 7 with autoimmune pancreatitis (AIP)], pancreatic cancer (PC) in 72, pancreatic neuroendocrine tumor (PNET) in 9, and normal pancreas in 8. The tissue elasticity distribution calculation was performed in real time, and the results were represented in color in fundamental B-mode imaging. In addition, we performed quantification using the SR (non-mass area/mass area).

Results

Elastography for all PC patients showed intense blue coloration, indicating malignant lesions. In contrast, MFP presented with a mixed coloration pattern of green, yellow, and low-intensity blue. Normal controls showed an even distribution of green to red. The mean SR was 23.66?±?12.65 for MFP and 39.08?±?20.54 for PC (P?Conclusions Endoscopic ultrasound elastography is a promising diagnostic tool for defining the tissue characteristics of pancreatic masses. In addition, semiquantitative analysis of elasticity using the SR may allow the differentiation of MFP from PC.     

Three-dimensional microarray compared with PCR-single-strand conformation polymorphism analysis/DNA sequencing for mutation analysis of K-ras codons 12 and 13

BACKGROUND: We developed a rapid, precise, and accurate microarray-based method that uses a three-dimensional platform for detection of mutations. METHODS: We used the PamChip microarray to detect mutations in codons 12 and 13 of K-ras in 15 cell lines and 81 gastric or colorectal cancer tissues. Fluorescein isothiocyanate-labeled PCR products were analyzed with the microarray. We confirmed the microarray results with PCR-single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. RESULTS: We could correctly identify wild-type, heterozygous, and homozygous mutant genotypes with the PamChip microarray in <3.5 h. The array data were consistent with those of PCR-SSCP analysis and DNA sequencing. All 15 cell lines and 80 of 81 clinical cancer specimens (98.8%; 95% confidence interval, 96.4-100%) were genotyped accurately with the microarray, a rate better than that of direct DNA sequencing (38.9%) or SSCP (93.8%). Only one clinical specimen was misdiagnosed as homozygous for the wild-type allele. Densitometric analysis of SSCP bands indicated that the content of the mutant allele in the specimen was approximately 16%. The PamChip microarray could detect mutant alleles representing more than 25% of the SSCP band proportions. Therefore, the limit for detection of mutant alleles by the PamChip microarray was estimated to be 16-25% of the total DNA. CONCLUSIONS: The PamChip microarray is a novel three-dimensional microarray system and can be used to analyze K-ras mutations quickly and accurately. The mutation detection rate was nearly 100% and was similar to that of PCR-SSCP together with sequencing analysis, but the microarray analysis was faster and easier.     

Clinicopathologic features of ampullary carcinoma without jaundice

GOALS: To evaluate clinicopathological features of ampullary carcinoma without jaundice. BACKGROUND:: Obstructive jaundice is the most common symptom of patients with ampullary carcinoma. However, some patients with ampullary carcinoma do not have jaundice at the time of diagnosis. STUDY: Clinicopathologic findings of 23 patients with ampullary carcinoma showing no visible jaundice (serum total bilirubin <3.0 mg/dL) and 38 patients with ampullary carcinoma showing jaundice at the time of diagnosis were retrospectively compared. RESULTS: Fifteen of 23 patients with nonjaundiced ampullary carcinoma complained of fever and/or abdominal pain. Five asymptomatic patients were found to have a dilated bile duct on screening ultrasound or to have a tumor-like swelling of the papilla of Vater during routine upper gastrointestinal endoscopy. There was no significant difference in age, sex, size, macroscopic type, histologic type, rates of duodenal invasion, pancreatic invasion, and lymph node metastasis, and prognosis between the two groups. The cumulative 5-year and 10-year survival rates of nonjaundiced patients were 70.2% and 49.0%, compared with 33.6% and 29.4% of jaundiced patients. Ten of the 23 nonjaundiced ampullary carcinomas (43%) were in Stage I, whereas 4 of the 38 jaundiced ampullary carcinomas (11%) were in Stage I (P < 0.01). Mechanisms of nonjaundice in ampullary carcinoma were suspected to be determinant by the infiltrating pattern of the carcinoma to the lower portion of the bile duct. CONCLUSIONS: Mechanisms of nonjaundice in ampullary carcinoma might be determined by the infiltrating pattern of the carcinoma to the lower portion of the bile. As a greater number of nonjaundiced ampullary carcinomas were in an early stage, detection of them may provide an improved clinical outcome.