Noriko Kamata

Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma

OBJECTIVES:Autoimmune pancreatitis (AIP) is a newly described entity with characteristic clinical, histologic, and morphologic changes, in which autoimmune mechanisms are involved in pathogenesis. However, difficulties can arise in the differentiation of AIP from pancreatic carcinoma. The aims of this study were to clarify clinical and radiologic features of AIP to elucidate areas of diagnostic confusion.METHODS:Clinical, serologic, and radiologic findings were evaluated in 17 patients with AIP.RESULTS:All 17 patients were initially suspected to have pancreatic carcinoma. The patients were predominantly elderly men who frequently presented with jaundice but without features of acute pancreatitis. Elevation of serum γ-globulin and IgG along with the presence of autoantibodies were usually evident, whereas serum tumor markers were elevated in 54% of cases. Stenosis of the bile duct was detected in 94% of cases. Diffuse enlargement of the pancreas and irregular narrowing of the main pancreatic duct were radiologically characteristic; however, segmental swelling and narrowing were detected in seven and two patients, respectively. In segmental cases, neither atrophy of the distal pancreas nor marked upstream dilation of the distal main pancreatic duct was observed.Angiographic abnormalities occurred in 54% of cases. Serologic and radiologic abnormalities showed considerable improvement with steroid therapy.CONCLUSIONS:Frequent stenosis of the bile duct, elevation of serum tumor markers, segmental pancreatic enlargement or narrowing of the main pancreatic duct, and angiographic abnormalities can cause confusion in the differential diagnosis of AIP and pancreatic carcinoma.

Evaluation of Deep Small Bowel Involvement by Double-Balloon Enteroscopy in Crohn's Disease

OBJECTIVES:Double-balloon enteroscopy (DBE) enables inspection of deep small bowel, and total small bowel examination can be performed by either antegrade or retrograde DBE. The aim of this study was to evaluate ileal involvement, which cannot be achieved using conventional colonoscopy, by DBE in patients with Crohns disease.METHODS:From December 2003 to September 2005, a total of 44 patients with Crohns disease underwent 53 examinations using DBE.RESULTS:Forty patients with Crohns disease, seven women and 33 men, underwent DBE, and the ileum was investigated in 38 patients. There were 25 cases of ileitis, 2 of colitis, and 13 of ileocolitis. Jejunal lesions were found in two and ileal lesions proximal to the terminal ileum were found in 24 patients with Crohns disease. DBE was superior to radiological study to detect aphthae, erosions, and small ulcers in the ileum. Small bowel stricture was demonstrated in six and nine patients with DBE and small bowel barium study (SBBS), respectively. An additional mucosal finding was demonstrated in one of the eight patients who underwent wireless capsule endoscopy, and one patient had a capsule removed by DBE that had become lodged because of an ileal stricture. One ileal perforation because of overtube balloon pressure occurred in 53 examinations of patients with Crohns disease (1.9%).CONCLUSION:DBE is useful to evaluate small bowel lesions in patients with Crohns disease; however, special attention should be paid to mesenteric longitudinal ulcers during insertion and the overtube balloon should not be inflated if a clear intestinal view is not possible.

Differentiation of autoimmune pancreatitis from pancreatic cancer by diffusion-weighted MRI.

OBJECTIVES:We sought to clarify the clinical utility of diffusion-weighted magnetic resonance imaging (DWI) for differentiating autoimmune pancreatitis (AIP) from pancreatic cancer.METHODS:Thirteen AIP patients underwent DWI before therapy, and six of them underwent DWI after steroid therapy. The extent and shape of high-intensity areas were compared with those of 40 pancreatic cancer patients. Apparent diffusion coefficient (ADC) values were calculated in the AIP area before and after steroid therapy in pancreatic cancer patients and in a normal pancreatic body.RESULTS:On DWI, AIP and pancreatic cancer were detected as high-signal intensity areas. The high-intensity areas were diffuse (n=4), solitary (n=6), and multiple (n=3) in AIP patients, but all pancreatic cancer patients showed solitary areas (P<0.001). A nodular shape was significantly more frequent in pancreatic cancer, and a longitudinal shape was more frequently found in AIP (P=0.005). ADC values were significantly lower in AIP (1.012±0.112 × 10−3 mm2/s) than in pancreatic cancer (1.249±0.113 × 10−3 mm2/s) and normal pancreas (1.491±0.162 × 10−3 mm2/s) (P<0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.075 × 10−3 mm2/s to distinguish AIP from pancreatic cancer. After steroid therapy, high-intensity areas on DWI disappeared or were markedly decreased, and the ADC values of the reduced pancreatic lesions increased almost to the values of normal pancreas.CONCLUSIONS:DWI is useful for detecting AIP and for evaluating the effect of steroid therapy. ADC values were significantly lower in AIP than in pancreatic cancer. An ADC cutoff value may be useful for distinguishing AIP from pancreatic cancer.

Strategy for differentiating autoimmune pancreatitis from pancreatic cancer.

Objectives: It is of utmost importance that autoimmune pancreatitis (AIP) be differentiated from pancreatic cancer (PC) because some AIP cases undergo unnecessary laparotomy or pancreatic resection on suspicion of PC. This study aimed to develop an appropriate strategy for differentiating between AIP and PC. Methods: Clinical, serological, and radiological features of 17 AIP patients forming a masslike lesion on pancreas head and 70 patients with pancreatic head cancer were compared. Results: Numerous findings can be used to distinguish between AIP and PC, and the following are more likely in AIP: fluctuating jaundice; elevated serum IgG4 levels; delayed enhancement of the enlarged pancreas and a capsule-like low-density rim on computed tomography; long or skipped narrowed portion with side branches of the main pancreatic duct without upstream dilatation on endoscopic retrograde pancreatography, extrapancreatic lesions, such as stenosis of the intrahepatic bile duct, salivary gland swelling, and retroperitoneal mass; and responsiveness to steroid therapy. Conclusions: In elderly male patients presenting with obstructive jaundice and a pancreatic mass, AIP should be considered in the differential diagnosis. Based on a combination of clinical, serological, and radiological findings, AIP can be differentiated from PC. An algorithm for management of patients with a masslike lesion on pancreas head is presented.

Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy.

Introduction Autoimmune pancreatitis (AIP) is a distinct clinical entity in which an autoimmune mechanism may be involved in pathogenesis. Aim To investigate salivary gland function in addition to pancreatic endocrine and exocrine function in patients with AIP, and to determine changes occurring after steroid therapy. Methodology Fasting serum glucose levels, oral glucose tolerance tests or glycosylated hemoglobin values were examined in 19 patients with AIP. N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test, sialochemistry and parotid gland scintigraphy were performed in 8 patients. Results Eight patients had evidence of DM. Steroid therapy subsequently improved insulin secretion and glycemic control in 3 of 5 patients treated. Pancreatic exocrine function was reduced in 88% of patients. Impaired pancreatic exocrine function improved after steroid therapy in 3 of 6 patients treated. The 3 patients also showed treatment-related improvement in endocrine function. Concentration of &bgr;2-microglobulin in saliva was significantly raised in patients with AIP compared with controls (P < 0.05). Ratio of cumulative peak count to injected radionuclide and washout ratio in parotid scintigraphy in patients with AIP was significantly lower than those of controls (P < 0.01). Salivary gland dysfunction improved after steroid therapy in all 5 patients treated. Conclusions Pancreatic endocrine and exocrine and salivary gland function were frequently impaired in patients with AIP, and steroid therapy was occasionally effective for these dysfunctions.

Toll-like receptor agonists stimulate human neutrophil migration via activation of mitogen-activated protein kinases

Human neutrophil migratory responses to Toll‐like receptor (TLR) agonists were studied using videomicroscopy. When challenged with lipopolysaccharide (LPS, TLR4 agonist) or N‐palmitoyl‐S‐[2,3‐bis(palmitoyloxy)‐(2RS)‐propyl]‐(R)‐cysteinyl‐seryl‐(lysyl)(3)‐lysine (P3CSK4, TLR2 agonist), neutrophils displayed enhanced motility, which was found to reflect increased random migration but not directed migration (chemotaxis). Enhanced neutrophil motility was detected within 10 min after stimulation with LPS or P3CSK4, and was sustained for more than 80 min. Stimulation of neutrophils with LPS or P3CSK4 resulted in the activation of extracellular signal‐regulated kinase (ERK) and p38 mitogen‐activated protein kinase (MAPK), which preceded neutrophil migration. TLR‐mediated neutrophil migration was strongly suppressed by pretreatment of cells with U0126 (MAPK/ERK kinase inhibitor) but not with U0124 (an inactive analogue of U0126) or SB203580 (a p38 MAPK inhibitor), and was almost completely abolished by pretreatment of cells with U0126 and SB203580 in combination. Randomly migrating neutrophils in response to LPS or P3CSK4 displayed directed migration when further challenged with gradient concentrations of N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP) or platelet‐activating factor (PAF). These findings indicate that TLR agonists stimulate human neutrophil migration via the activation of ERK and p38 MAPK, and FMLP‐ or PAF‐induced neutrophil chemotaxis is not affected by the pre‐exposure of cells to TLR agonists.

Salivary gland involvement in chronic pancreatitis of various etiologies.

OBJECTIVE:Both the pancreas and salivary glands show many histological and functional similarities. Recently, autoimmune pathogenesis has been postulated in some chronic pancreatitis cases. To examine whether a cell-mediated phenomenon involving the pancreas has a secondary effect on the salivary glands, we assessed the frequency of salivary gland dysfunction in patients with chronic pancreatitis of various etiologies.METHODS:Function of the salivary glands was examined by sialochemistry and salivary gland scintigraphy in patients with chronic pancreatitis (n = 33), Sjogrens syndrome (n = 45), and controls (n = 28). Etiologies of chronic pancreatitis were alcoholic (19 cases), idiopathic (seven cases), and autoimmune (seven cases). Concentrations of Na+, amylase, and β2-microglobulin in saliva were investigated. In submandibular and parotid gland scintigraphy, time-activity curves were generated, and the ratios of peak count density and washout were calculated.RESULTS:Concentrations of Na+ in saliva of patients with idiopathic chronic pancreatitis and of β2-microglobulin in saliva of patients with idiopathic and autoimmune chronic pancreatitis were significantly elevated than those of the control group. In submandibular and parotid gland scintigraphy, the peak count density ratio of patients with all chronic pancreatitis and washout ratio of patients with alcoholic and idiopathic chronic pancreatitis were significantly lower than those of the control group.CONCLUSIONS:Salivary gland function was frequently impaired in the course of chronic pancreatitis of various etiologies. Salivary gland dysfunction might be the result of a common pathophysiological effect of alcohol in patients with alcoholic chronic pancreatitis and the aggressive immune mechanism against the pancreatic and the salivary ducts in patients with autoimmune and idiopathic chronic pancreatitis.

Phenotypical and functional study of ghrelin and its receptor in the pathogenesis of Crohn's disease

Background: Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor (GHSR), has been demonstrated to possess multiple functions including antiinflammatory effects. The aim of this study was to investigate the expression of ghrelin and GHSR and the function of ghrelin in inflammatory bowel disease (IBD). Methods: The expression of ghrelin and GHSR mRNA was quantified in mucosal biopsy specimens from 9 controls, 15 patients with Crohns disease (CD), and 15 patients with ulcerative colitis (UC) using quantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR). The locations of ghrelin and GHSR were investigated immunohistochemically in surgically resected specimens. We also evaluated the percentage of GHSR‐positive peripheral blood mononuclear cells (PBMCs) in healthy controls and patients with CD by flow cytometry. In addition, we investigated the immunoregulatory function of ghrelin in peripheral blood T cells. Results: Ghrelin mRNA levels in colonic mucosa of IBD were higher than control level. The GHSR‐1a mRNA level in active CD was also significantly higher than the control level. Ghrelin and GHSR‐1a were expressed on CD3‐ and CD68‐positive cells. The percentage of GHSR‐1a‐positive peripheral blood T cells in patients with CD was significantly higher than the control level. Stimulation of human T cells with ghrelin increased levels of IL‐4 and IL‐13 proteins and decreased levels of IFN‐gamma protein. Reactivity to ghrelin was low in CD compared with the control level. Conclusions: Our findings demonstrate that ghrelin may play an important role in the immune system in CD. The dysregulation of reactivity of T cells induced by ghrelin suggests that ghrelin might participate in the pathogenesis of CD.

Usefulness of Double-Balloon Endoscopy in the Diagnosis of Malignant Small-Bowel Tumors

BACKGROUND & AIMS Double-balloon endoscopy (DBE) enables endoscopic and histopathologic diagnosis of malignant small-bowel tumors (MSBT). This study examined the clinical features of patients with MSBT and evaluated the usefulness of DBE in the diagnosis of MSBT. METHODS We retrospectively examined consecutive DBE studies of 358 patients who underwent DBE in our hospital between December 2003 and October 2007 because of suspected or established small-bowel disease. RESULTS Fourteen patients with MSBT were diagnosed by DBE. The most common type was primary adenocarcinoma (8 patients), followed by metastatic carcinoma (3 patients) and malignant lymphoma (3 patients). Half of these patients presented with obscure gastrointestinal bleeding (OGIB). Histopathologic diagnosis was obtained in 11 of 14 patients. CONCLUSIONS Of 180 patients with OGIB, MSBT accounted for only 3.9%, however, 50% of patients with MSBT presented with OGIB. OGIB is an important clinical feature of small-bowel malignancy, which can be diagnosed by DBE.

A comparative study of single-incision versus conventional multiport laparoscopic ileocecal resection for Crohn's disease with strictures

Single‐incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multiport laparoscopic surgery. Recently, this technique has been applied to colorectal disease. However, there have been few reports about its application to Crohns disease (CD) in the literature. The aim of this study is to describe our early experience with SILS for 11 patients with CD and make comparisons with the conventional multiport laparoscopic surgery.