Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis： A prospective study using IgG4-immunostaining

AIM: To examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoimmune pancreatitis (AIP) patients. METHODS: The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma (n = 3) and chronic alcoholic pancreatitis (n = 2)] was immunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2 patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochemically examined. RESULTS: Moderate or severe lymphoplasmacytic infiltration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells (≥10/HPF), was observed in the major duodenal papilla of all 3 patients with AIP. The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with AIP, but in controls, there were only a few (≤3/HPF) IgG4-positive plasma cells infiltrating the major duodenal papilla. CONCLUSIONS: An abundant infiltration of IgG4-positive plasma cells is specifically detected in the major duodenal papilla of patients with AIP. Although this is a preliminary study, IgG4-immunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIP.     

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis: A prospective study using TgG4-immunostaining

AIM: To examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoirnrnune pancreatitis (AIP)patients.METHODS: The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma (n = 3) and chronic alcoholic pancreatitis (n = 2)] was irnrnunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochernically examined.RESULTS: Moderate or severe lyrnphoplasrnacytic infiltration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells (≥10/HPF),was observed in the major duodenal papilla of all 3 patients with AIP. The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with AIP, but in controls, there were only a few (≤3/HPF) IgG4-positive plasma cells infiltrating the major duodenal papilla.CONCLUSIONS: An abundant infiltration of IgG4-positive plasma cells is specifically detected in the major duodenal papilla of patients with AIP. Although this is a preliminary study, IgG4-irnmunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIP.     

Groove pancreatitis and pancreatic heterotopia in the minor duodenal papilla

Groove pancreatitis is a rare form of segmental chronic pancreatitis that involves the anatomic space between the head of the pancreas, the duodenum, and the common bile duct. We report 2 cases of groove pancreatitis with pancreatic heterotopia in the minor papilla. Patients were a 44-year-old woman and a 47-year-old man. Both had a past history of alcohol consumption and presented with abdominal pain, vomiting, and weight loss caused by duodenal stenosis. Abdominal computed tomography revealed thickening of the duodenal wall and enlargement of the pancreatic head in both patients. In 1 patient, ultrasound endoscopy showed a dilated duct in the head of the pancreas. Pancreaticoduodenectomy was performed to rule out pancreatic adenocarcinoma and because of the severity of the symptoms. In both cases, gross and microscopic examinations showed fibrous scar of the groove area. The Santorini duct was dilated and contained protein plugs in both patients, with abscesses in 1 of them. In both cases, there were microscopic foci of heterotopic pancreas with mild fibrosis in the wall of the minor papilla. Groove pancreatitis is often diagnosed in middle-aged alcoholic men presenting with clinical symptoms caused by duodenal stenosis. The pathogenesis of this rare entity could be because of disturbance of the pancreatic secretion through the minor papilla. Pancreatitis in heterotopic pancreas located in the minor papilla and chronic consumption of alcohol seem to be important pathogenic factors.     

Enzyme activities in the gastric mucosa in duodenal ulcer patients

In a series of 45 consecutive duodenal ulcer patients (DU) the activities of 10 marker enzymes from the brush border, basolateral membrane, mitochondria, and lysosomes were determined by analysis of homogenized material taken with biopsy forceps through an endoscope from the antral and body part of the stomach. They were compared with the enzyme activities determined in controls with similar types of gastritis but without any evidence of peptic ulcer disease. All the DU patients had gastritis in the antral mucosa. In the body part, about 30% had gastritis. In the antral mucosa of DU patients the activities of the membrane and lysosomal enzymes were mostly increased when compared with the controls. In the gastric body mucosa of DU patients the activities of the lysosomal enzymes were mostly increased, whereas most of the membrane enzymes showed unchanged activities when compared with the corresponding controls. Monoamine oxidase activities were decreased or unaltered in both regions in these patients. The finding of enzymatic changes in the gastric mucosa of DU patients gives further support to an altered mucosal metabolism in these patients.     

The effect of lidocaine sprayed on the major duodenal papilla on the frequency of post-ERCP pancreatitis

BACKGROUND: Acute pancreatitis remains a serious cause of ERCP-related morbidity. Topical application of lidocaine reportedly blunts cholecystokinin release from intestinal mucosa and reduces sphincter of Oddi spasm. A randomized trial was conducted to evaluate the effect of lidocaine sprayed on the major duodenal papilla on the frequency of post-ERCP pancreatitis. Secondary outcomes evaluated were ease of cannulation and severity of post-ERCP pancreatitis. METHODS: Patients undergoing ERCP were randomized in blocks of 6 to have 10 mL of either 1% lidocaine or normal saline solution sprayed on the major papilla before cannulation. Patients were observed for the development of post-ERCP pancreatitis. Patient history- and procedure-related variables were recorded. RESULTS: A total of 326 patients were enrolled, of whom 32 were excluded after randomization but before analysis. Of patients analyzed, 145 were randomized to treatment with lidocaine and 149 to placebo. No patient was lost to follow-up. There was no significant difference noted in patient history- or procedure-related variables. Seven patients in the lidocaine group and 5 in the placebo group developed post-ERCP pancreatitis (p=0.73). Ease of cannulation did not differ between the two groups. CONCLUSIONS: Lidocaine sprayed on the major papilla does not decrease the frequency of post-ERCP pancreatitis.     

Endoscopic management of adenoma of the major duodenal papilla

BACKGROUND: It is well established that adenoma of the major duodenal papilla has a potential for malignant transformation. Standard treatment has been surgical (duodenotomy/local resection, pancreaticoduodenectomy). Endoscopic management is described, but there is no established consensus regarding the approach to papillectomy or the need for surveillance. This study describes endoscopic management and long-term follow-up of papillary tumors by 4 groups of expert pancreaticobiliary endoscopists. METHODS: Consecutive patients with papillary tumors referred to 4 pancreaticobiliary endoscopy centers for evaluation for endoscopic papillectomy were reviewed. For each patient, an extensive questionnaire was completed, which included 19 preoperative and 15 postoperative data points. A total of 103 patients (53 women, 50 men, age range 24-93) who underwent attempted endoscopic resection were included. Of these, 72 had sporadic adenoma, and the remaining patients had familial adenomatous polyposis, including Gardner's variant. Presenting symptoms were jaundice/cholangitis/pain (n=59), pancreatitis (n=18), and bleeding (n=12). Twenty-six patients were asymptomatic. RESULTS: Endoscopic treatment was successful, long term, in 83 patients (80%) and failed (initial failure or recurrent tumor) in 20 (20%) patients. Success was significantly associated with older age (54.7 [16.6] vs. 46.6 [21.7] years; p=0.08) and smaller lesions (21.1 [8.3] vs. 29.7 [7.2] mm; p<0.0001). Success rate was higher for sporadic lesions compared with genetically determined lesions (63 of 72 [86%] vs. 20 of 31 [67%]; p=0.02). There were 10 initial failures, which was more common for sporadic lesions (7 of 10). The overall success rate for papillectomy was similar in patients who had adjuvant thermal ablation (81%) compared with those who did not (78%). However, recurrence (n=10) was more common in the former group (9 of 10, [90%]; p=0.22). Complications (n=10) included acute pancreatitis (n=5), bleeding (n=2), and late papillary stenosis (n=3). Acute pancreatitis was more common in patients who did not have pancreatic duct stents placed (17% vs. 3.3%). Papillary stenosis was more frequent without short-term pancreatic duct stent placement (15.4% vs. 1.1%), although the difference was not statistically significant, because this complication was infrequent. CONCLUSIONS: Endoscopic treatment of papillary adenoma in selected patients appears to be highly successful. The majority can undergo complete resection after ERCP. In expert hands, complications are infrequent and may be avoided by routine placement of a pancreatic duct stent.     

Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia

Nonulcer dyspepsia is a common clinical syndrome whose etiology is unknown. The sensitivity of the gastric mucosa to acid and duodenal contents in 18 patients with nonulcer dyspepsia was studied. The patients had a normal upper gastrointestinal endoscopy and biopsy specimens were obtained for determination of Helicobacter pylori status. Fifteen of the 18 patients were infected with H. pylori. All patients underwent intubation with double-lumen tube and collection of cholecystokinin-stimulated pancretico-biliary secretions. Subsequently, normal saline, 0.1N hydrochloric acid, and autologous duodenal secretions were infused into the stomach in a randomized blinded fashion. A positive response was defined as the production of epigastric pain by acid and/or bile but not by saline. By this definition, only 6 patients (33%) had a positive response and none had reproduction of their usual symptoms. In patients with a negative response, only 4 remained asymptomatic during all infusions. The remaining 8 had symptoms during infusion of saline, 7 of whom also had symptoms during infusion of acid and/or duodenal secretions. Two of these patients had reproduction of their usual symptoms. In conclusion, the gastric mucosa in patients with nonulcer dyspepsia is not abnormally sensitive to acid or duodenal contents.     

The clinical significance of papillitis of the major duodenal papilla

BACKGROUND: This study investigated the clinical significance of papillitis of the major duodenal papilla and analyzed the correlation between endoscopic and histologic papillitis in patients with biliary or pancreatic disorders. METHODS: Eighty-seven patients and 12 healthy control subjects were enrolled. The endoscopic appearance of papillitis was classified by two blinded endoscopists, and biopsy specimens were taken of the papilla. Various factors were prospectively analyzed to identify any relationship with the endoscopic severity of the papillitis. RESULTS: By univariate analysis, a clinically acute inflammatory condition and elevation of serum transaminase levels were significantly associated with moderate and severe endoscopic papillitis (p < 0.05). However, by multivariate analysis, only a clinically acute inflammatory condition was significantly associated with moderate and severe endoscopic papillitis (p < 0.001). The endoscopic severity of papillitis was poorly correlated with monocyte infiltration, but there was a good correlation with neutrophil infiltration. Moderate and severe papillitis were not observed in healthy volunteers. CONCLUSIONS: Moderate and severe endoscopic papillitis were significantly more common in patients with biliary or pancreatic disorders plus a clinically acute inflammatory condition, whereas moderate and severe papillitis were not observed in healthy volunteers. Moderate and severe endoscopic papillitis are characteristic of biliary or pancreatic disorders.     

Endoscopic findings of the duodenal papilla in patients with pancreaticobiliary maljunction

Background: To our knowledge this is the first report describing the relation between the form of the duodenal papilla and the pancreaticobiliary maljunction (PBM). Methods: The duodenal papilla was studied endoscopically in 46 patients with PBM and in 80 patients without PBM. Results: The duodenal papilla was classified into three types by three independent endoscopists. Conclusion: The oral protrusion of the duodenal papilla in patients with PBM was shorter or absent compared with the duodenal papilla in patients without PBM.     

Hypothyroidism in patients with autoimmune pancreatitis

AIM To examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis(AIP) patients.METHODS We examined thyroid function in 77 patients with type 1 AIP(50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined. RESULTS Eight patients(10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine(FT4) and high thyroid stimulating hormone(TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine(FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG 4-related disease(IgG4-RD); presence of antithyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP.CONCLUSION Hypothyroidism was observed in 8(10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.