Cellular retinoic acid binding protein 1 protects mice from high-fat diet-induced obesity by decreasing adipocyte hypertrophy.

OBJECTIVES: Obesity, an emerging global health issue, involves numerous factors; understanding its underlying mechanisms for prevention and therapeutics is urgently needed. Cellular retinoic acid binding protein 1 (Crabp1) knockout (CKO) mice exhibit an obese phenotype under normal diet (ND) feedings, which prompted us to propose that Crabp1 could play a role in modulating adipose tissue development/homeostasis. Studies were designed to elucidate the underlying mechanism of Crabp1's action in reducing obesity. SUBJECTS/METHODS: In animal studies, 6 weeks old male wild type and CKO mice were fed with ND or high-fat diet (HFD) for 10 weeks. Body weight and food intake were regularly monitored. Glucose tolerance test and biological parameters of plasma (glucose and insulin levels) were measured after 10 weeks of ND vs. HFD feedings. Visceral adipose tissues were collected for histological and molecular analyses to determine affected signaling pathways. In cell culture studies, the 3T3L1 adipocyte differentiation model was used to examine and validate relevant signaling pathways. RESULTS: CKO mice, compared to WT mice, gained more body weight, exhibited more elevated fasting plasma glucose levels, and developed more severe impaired glucose tolerance under both ND and HFD. Histological examination revealed readily increased adipocyte hypertrophy and adipose tissue inflammation under HFD feedings. In 3T3L1 adipocytes, Crabp1 silencing enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, accompanied by elevated markers and signaling pathways of lipid accumulation and adipocyte hypertrophy. CONCLUSIONS: This study identifies Crabp1's physiological role against the development of obesity. The protective function of CRABP1 is likely attributed to its classically proposed (canonical) activity as a trap for RA, which will reduce RA availability, thereby dampening RA-stimulated ERK1/2 activation and adipocyte hypertrophy. The results suggest Crabp1 as a potentially new therapeutic target in managing obesity and metabolic diseases.

Correction to: Cellular retinoic acid binding protein 1 protects mice from high-fat diet-induced obesity by decreasing adipocyte hypertrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Biochemical markers of striatal desensitization in cortical-limbic hyperglutamatergic TS- & OCD-like transgenic mice.

Tics and compulsions in comorbid Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD) are associated with chronic hyperactivity of parallel cortico/amygdalo-striato-thalamo-cortical (CSTC) loop circuits. Comorbid TS- & OCD-like behaviors have likewise been observed in D1CT-7 mice, in which an artificial neuropotentiating transgene encoding the cAMP-elevating intracellular subunit of cholera toxin (CT) is chronically expressed selectively in somatosensory cortical & amygdalar dopamine (DA) D1 receptor-expressing neurons that activate cortico/amygdalo-striatal glutamate (GLU) output. We've now examined in D1CT-7 mice whether the chronic GLU output from their potentiated cortical/limbic CSTC subcircuit afferents associated with TS- & OCD-like behaviors elicits desensitizing neurochemical changes in the striatum (STR). Microdialysis-capillary electrophoresis and in situ hybridization reveal that the mice's chronic GLU-excited STR exhibits pharmacodynamic changes in three independently GLU-regulated measures of output neuron activation, co-excitation, and desensitization, signifying hyperactive striatal CSTC output and compensatory striatal glial and neuronal desensitization: 1) Striatal GABA, an output neurotransmitter induced by afferent GLU, is increased. 2) Striatal d-serine, a glial excitatory co-transmitter inhibited by afferent GLU, is decreased. 3) Striatal Period1 (Per1), which plays a non-circadian role in the STR as a GLU + DA D1- (cAMP-) dependent repressor thought to feedback-inhibit GLU + DA- triggered ultradian urges and motions, is transcriptionally abolished. These data imply that chronic cortical/limbic GLU excitation of the STR desensitizes its co-excitatory d-serine & DA inputs while freezing its GABA output in an active state to mediate chronic tics and compulsions - possibly in part by abolishing striatal Per1-dependent ultradian extinction of urges and motions.

Back to the Future: Circuit-testing TS & OCD.

A decade before the rise of optogenetics, the first behavioral "circuit-test" - transgenically modulating the output of a genetically-specified brain circuit element to examine its effect on behavior - was performed. The behaviors emulated in those mice were comorbid tics and compulsions, elicited by a gene borrowed from cholera bacteria and tailored to intracellularly neuropotentiate glutamatergic somatosensory cortical and limbic output neurons of cortico/amygdalo-striato-thalamo-cortical (CSTC) loop circuits. Two decades later, cutting-edge chemogenetic and optogenetic methods are again being devoted to further characterize the circuits thought to trigger, mediate, aggravate, or ameliorate TS & OCD symptoms. These tour de force studies support essential roles in tics and compulsions for topographically-parallel corticostriatal and amygdalar glutamatergic output neurons; their target dorsal striatal & ventral striatal (nucleus accumbens) medium spiny neurons (MSNs) of the direct striatothalamic (urge & motor activating) vs. indirect striatopallidal (urge & motor suppressing) output pathways; and their converging modulatory dopaminergic and histaminergic afferents. Going "back to the future" to circuit-map tics and compulsions will give us precision targets for future psychological, drug, medtech, and gene therapies; look for "dopamine bypasses" on your next trip in the DeLorean.

"Hyperglutamatergic cortico-striato-thalamo-cortical circuit" breaker drugs alleviate tics in a transgenic circuit model of Tourette׳s syndrome.

The brain circuits underlying tics in Tourette׳s syndrome (TS) are unknown but thought to involve cortico/amygdalo-striato-thalamo-cortical (CSTC) loop hyperactivity. We previously engineered a transgenic mouse "circuit model" of TS by expressing an artificial neuropotentiating transgene (encoding the cAMP-elevating, intracellular A1 subunit of cholera toxin) within a small population of dopamine D1 receptor-expressing somatosensory cortical and limbic neurons that hyperactivate cortico/amygdalostriatal glutamatergic output circuits thought to be hyperactive in TS and comorbid obsessive-compulsive (OC) disorders. As in TS, these D1CT-7 ("Ticcy") transgenic mice׳s tics were alleviated by the TS drugs clonidine and dopamine D2 receptor antagonists; and their chronic glutamate-excited striatal motor output was unbalanced toward hyperactivity of the motoric direct pathway and inactivity of the cataleptic indirect pathway. Here we have examined whether these mice׳s tics are countered by drugs that "break" sequential elements of their hyperactive cortical/amygdalar glutamatergic and efferent striatal circuit: anti-serotonoceptive and anti-noradrenoceptive corticostriatal glutamate output blockers (the serotonin 5-HT2a,c receptor antagonist ritanserin and the NE alpha-1 receptor antagonist prazosin); agmatinergic striatothalamic GABA output blockers (the presynaptic agmatine/imidazoline I1 receptor agonist moxonidine); and nigrostriatal dopamine output blockers (the presynaptic D2 receptor agonist bromocriptine). Each drug class alleviates tics in the Ticcy mice, suggesting a hyperglutamatergic CSTC "tic circuit" could exist in TS wherein cortical/amygdalar pyramidal projection neurons׳ glutamatergic overexcitation of both striatal output neurons and nigrostriatal dopaminergic modulatory neurons unbalances their circuit integration to excite striatothalamic output and create tics, and illuminating new TS drug strategies.

Injecting engineered anti-inflammatory macrophages therapeutically induces white adipose tissue browning and improves diet-induced insulin resistance.

We recently exploited a transgenic approach to coerce macrophage anti-inflammatory M2 polarization in vivo by lowering Receptor Interacting Protein 140 (RIP140) level in macrophages (mφRIP140KD), which induced browning of white adipose tissue (WAT). In vitro, conditioned medium from cultured adipose tissue macrophages (ATMs) of mφRIP140KD mice could trigger preadipocytes' differentiation into beige cells. Here we describe a cell therapy for treating high fat diet (HFD)-induced insulin resistance (IR). Injecting M2 ATMs retrieved from the WAT of mφRIP140KD mice into HFD-fed obese adult wild-type mice effectively triggers their WAT browning, reduces their pro-inflammatory responses, and improves their insulin sensitivity. These data provide a proof-of-concept that delivering engineered anti-inflammatory macrophages can trigger white fat browning, stimulate whole-body thermogenesis, and reduce obesity-associated IR.

M1-M2 balancing act in white adipose tissue browning - a new role for RIP140.

A "Holy Grail" sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophages that migrate into adipose deposits. The coregulator, Receptor Interacting Protein 140 (RIP140), plays a key role in regulating this communication. In mice on a high-fat diet, the level of RIP140 in macrophages is dramatically elevated to activate their inflammatory M1 polarization and enhance their recruitment into WAT, facilitating IR. Conversely, lowering the level of RIP140 in macrophages not only reduces M1 macrophages but also expands alternatively polarized, anti-inflammatory M2 macrophages, triggering white adipose tissue browning, fat burning, and restoration of insulin sensitivity. This suggests a potential therapeutic strategy for reversing IR, obesity, and atherosclerotic or even cosmetic fat deposits: therapeutic browning of white adipose deposits by diminishing RIP140 levels in macrophages.

Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis.

BACKGROUND & AIMS: Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. METHODS: We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). RESULTS: The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. CONCLUSIONS: The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP.

Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis.

BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is a complex inflammatory disorder associated with multiple genetic and environmental factors. In individuals without cystic fibrosis (CF), variants of CFTR that inhibit bicarbonate conductance but maintain chloride conductance might selectively impair secretion of pancreatic juice, leading to trypsin activation and pancreatitis. We investigated whether sequence variants in the gene encoding the pancreatic secretory trypsin inhibitor SPINK1 further increase the risk of pancreatitis in these patients. METHODS: We screened patients and controls for variants in SPINK1 associated with risk of chronic pancreatitis and in all 27 exons of CFTR. The final study group included 53 patients with sporadic ICP, 27 probands with familial ICP, 150 unrelated controls, 375 additional controls for limited genotyping. CFTR wild-type and p.R75Q were cloned and expressed in HEK293 cells, and relative conductances of HCO(3)(-) and Cl(-) were measured. RESULTS: SPINK1 variants were identified in 36% of subjects and 3% of controls (odds ratio [OR], 18.1). One variant of CFTR not associated with CF, p.R75Q, was found in 16% of subjects and 5.3% of controls (OR, 3.4). Coinheritance of CFTR p.R75Q and SPINK1 variants occurred in 8.75% of patients and 0.38% of controls (OR, 25.1). Patch-clamp recordings of cells that expressed CFTR p.R75Q showed normal chloride currents but significantly reduced bicarbonate currents (P = .0001). CONCLUSIONS: The CFTR variant p.R75Q causes a selective defect in bicarbonate conductance and increases risk of pancreatitis. Coinheritance of p.R75Q or CF causing CFTR variants with SPINK1 variants significantly increases the risk of ICP.

Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.

OBJECTIVE: To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS: This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS: Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS: This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.

Advanced imaging of chronic pancreatitis.

Chronic pancreatitis is characterized by continuing inflammation, destruction, and irreversible morphological changes in the pancreatic parenchyma and ductal anatomy. These changes lead to chronic pain and/or loss of function. Although these definitions are simple, the clinical diagnosis of chronic pancreatitis remains difficult to make, especially for early disease. Routine imaging modalities such as transabdominal ultrasound and standard CT scans are insensitive for depicting early disease, and detect only advanced chronic pancreatitis. Advances in imaging modalities including CT, MRI with gadolinium contrast enhancement, MRI with magnetic resonance cholangiopancreatography (MRI/MRCP), MRI/MRCP with secretin-stimulation (S-MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS) allow earlier diagnosis of chronic pancreatitis. This article reviews the recognized findings, advantages, and disadvantages of the various imaging modalities in the management of chronic pancreatitis, specifically CT, MRI with or without MRCP and/or S-MRCP, ERCP, and EUS.

MRI and S-MRCP findings in patients with suspected chronic pancreatitis: correlation with endoscopic pancreatic function testing (ePFT).

PURPOSE: To review magnetic resonance imaging (MRI) and secretin stimulated magnetic resonance cholangiopancreatography (S-MRCP) findings of patients with suspected chronic pancreatitis and compare them with endoscopic pancreatic function testing (ePFT). MATERIALS AND METHODS: MRI and S-MRCP findings of 36 patients with clinically suspected chronic pancreatitis were reviewed. Baseline ductal changes, duodenal filling grades, and pancreatic duct caliber change (PDC) on S-MRCP, mean values of pancreatic anteroposterior (AP) diameter, signal intensity ratio (SIR) between pancreas and the spleen on T1-weighted fat saturated images, and arterial to venous (A/V) enhancement ratios were compared between groups of normal and abnormal pancreatic exocrine function determined by ePFT. RESULTS: All patients (n = 24) with normal ePFT (HCO(3) >80 mEq/L) had grade 3 normal duodenal filling. Patients with abnormal ePFT (HCO(3) <80 mEq/L) (n = 12) had grade 1 (n = 1) and grade 2 (n = 11) diminished duodenal filling (P < 0.0001). PDC was 1.51 in the normal ePFT group versus 1.27 in the abnormal ePFT group (P = 0.01). No significant differences were found in terms of mean pancreatic AP diameter (21.8 vs. 19.8 cm), SIR (1.59 vs. 1.44), and A/V (1.08 vs. 1.01) between groups of normal/abnormal pancreatic exocrine function. CONCLUSION: Despite discrepancies between pancreatic exocrine function and the findings on standard MRI/MRCP, the S-MRCP findings are comparable to ePFT in the evaluation of chronic pancreatitis.

Smoking is underrecognized as a risk factor for chronic pancreatitis.

BACKGROUND/AIMS: Smoking is an established risk factor for chronic pancreatitis (CP). We sought to identify how often and in which CP patients physicians consider smoking to be a risk factor. METHODS: We analyzed data on CP patients and controls prospectively enrolled from 19 US centers in the North American Pancreatitis Study-2. We noted each subject's self-reported smoking status and quantified the amount and duration of smoking. We noted whether the enrolling physician (gastroenterologist with specific interest in pancreatology) classified alcohol as the etiology for CP and selected smoking as a risk factor. RESULTS: Among 382/535 (71.4%) CP patients who were self-reported ever smokers, physicians cited smoking as a risk factor in only 173/382 (45.3%). Physicians cited smoking as a risk factor more often among current smokers, when classifying alcohol as CP etiology, and with higher amount and duration of smoking. We observed a wide variability in physician decision to cite smoking as a risk factor. Multivariable regression analysis however confirmed that the association of CP with smoking was independent of physician decision to cite smoking as a risk factor. CONCLUSIONS: Physicians often underrecognize smoking as a CP risk factor. Efforts are needed to raise awareness of the association between smoking and CP. and IAP.

Magnetic resonance imaging in pancreatitis.

Pancreatitis can occur in acute and chronic forms. Magnetic resonance imaging (MRI) plays an important role in the early diagnosis of both conditions and complications that may arise from acute or chronic inflammation of the gland. Standard MRI techniques including T1-weighted and T2-weighted fat-suppressed imaging sequences together with contrast-enhanced imaging can both aid in the diagnosis of acute pancreatitis and demonstrate complications as pseudocysts, hemorrhage, and necrosis. Combined use of MRI and MR cholangiopancreatography can show both parenchymal findings that are associated with chronic pancreatitis including pancreatic size and signal and arterial enhancements, all of which are diminished in chronic pancreatitis. The degree of main pancreatic duct dilatation and/or the number of side branch ectasia determines the diagnosis of chronic pancreatitis and its severity. In this paper, we report the spectrum of imaging findings of acute and chronic pancreatitis on MRI and MR cholangiopancreatography.

Magnetic resonance imaging in pancreas transplantation.

Magnetic resonance imaging (MRI) plays an important role in the evaluation of pancreas transplantation. Standard MRI, magnetic resonance angiography, and MR cholangiopancreatography can demonstrate the changes of the anatomy after transplantation. Vascular complications are assessed by MR angiography. Magnetic resonance cholangiopancreatography reveals ductal changes resulting from acute and/or chronic rejection and determines leaks with the use of a secretin-stimulated MR cholangiopancreatography. Serial contrast-enhanced MRI may detect the diminished perfusion that is related to the graft rejection or vascular complications. In this paper, we reviewed types of pancreas transplantation procedures, complications that arise in a short and/or a long term after the transplantation, and their assessment by MRI.

The effect of prior sphincterotomy on the secretin-stimulated magnetic resonance cholangiopancreatography (s-MRCP).

RATIONALE AND OBJECTIVES: A lack of pancreatic duct compliance and decreased duodenal filling on secretin-stimulated magnetic resonance cholangiopancreatography (s-MRCP) has been noted in patients with chronic pancreatitis. Whether endoscopic sphincterotomy can affect pancreatic duct compliance and duodenal filling on diagnostic s-MRCP is unknown. MATERIALS AND METHODS: A retrospective review of patients referred to the authors' clinic from December 2006 to December 2007 was performed. Those patients with no evidence of chronic pancreatitis who underwent s-MRCP were studied. Findings on s-MRCP were analyzed, specifically noting change in pancreatic duct diameter size from baseline to maximum dilation and duodenal filling after secretin administration (0.2 microg/kg intravenous dose of human secretin). RESULTS: Of the 34 patients studied, 12 underwent endoscopic sphincterotomy, and 22 had intact sphincters of Oddi. In the sphincterotomy group, there was a mean change of 0.2 cm (range, 0.0-0.4 cm), while in the nonsphincterotomy group, the mean change was 0.9 cm (range, 0.3-2.0 cm) after secretin administration. The difference was significant (P < .005). CONCLUSION: Endoscopic sphincterotomy significantly decreases pancreatic duct dilation in response to secretin on s-MRCP. However, further studies are required to determine the effect sphincterotomy has on the amount of duodenal filling and the rate at which duodenal filling occurs.

Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis.

BACKGROUND: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are associated with alcohol consumption and cigarette smoking. The etiology of RAP and CP is complex, and effects of alcohol and smoking may be limited to specific patient subsets. We examined the current prevalence of alcohol use and smoking and their association with RAP and CP in patients evaluated at US referral centers. METHODS: The North American Pancreatitis Study 2, a multicenter consortium of 20 US centers, prospectively enrolled 540 patients with CP, 460 patients with RAP, and 695 controls from 2000 to 2006. Using self-reported monthly alcohol consumption during the maximum lifetime drinking period, we classified subjects by drinking status: abstainer, light drinker (< or =0.5 drink per day), moderate drinker (women, >0.5 to 1 drink per day; men, >0.5 to 2 drinks per day), heavy drinker (women, >1 to <5 drinks per day; men, >2 to <5 drinks per day), or very heavy drinker (> or =5 drinks per day for both sexes). Smoking was classified as never, past, or current and was quantified (packs per day and pack-years). RESULTS: Overall, participants' mean (SD) age was 49.7 (15.4) years; 87.5% were white, and 56.5% were women. Approximately one-fourth of both controls and patients were lifetime abstainers. The prevalence of very heavy drinking among men and women was 38.4% and 11.0% for CP, 16.9% and 5.5% for RAP, and 10.0% and 3.6% for controls. Compared with abstaining and light drinking, very heavy drinking was significantly associated with CP (odds ratio, 3.10; 95% confidence interval, 1.87-5.14) after controlling for age, sex, smoking status, and body mass index. Cigarette smoking was an independent, dose-dependent risk factor for CP and RAP. CONCLUSIONS: Very heavy alcohol consumption and smoking are independent risks for CP. A minority of patients with pancreatitis currently seen at US referral centers report very heavy drinking.

Acute pancreatic graft fistula and peripancreatic fluid collection: demonstration by secretin-stimulated MRI.

Peripancreatic fluid collections are among the common post pancreas transplant complications, which are mainly due to leakage from the anastomosis site to bowel and graft pancreatitis. Differentiation between these two entities is important because they are treated differently. In this case, secretin stimulated magnetic resonance cholangiopancreatography revealed gradual intraperitoneal fluid collection and accumulation of fluid in small bowel excluded leakage from the anastomosis of the pancreas to bowel and changed the management from surgery to medical treatment.

Pancreatic diffusion-weighted imaging (DWI): comparison between mass-forming focal pancreatitis (FP), pancreatic cancer (PC), and normal pancreas.

PURPOSE: To compare diffusion-weighted imaging (DWI) findings and the apparent diffusion coefficient (ADC) values of pancreatic cancer (PC), mass-forming focal pancreatitis (FP), and the normal pancreas. MATERIALS AND METHODS: DWI (b = 0 and 600 seconds/mm(2)) findings of 14 patients with mass-forming FP proven by histopathology and or clinical follow-up, 10 patients with histopathologically-proven PC, and 14 subjects with normal pancreatic exocrine function and normal imaging findings were retrospectively evaluated. ADC values of the masses, the remaining pancreas, and the normal pancreas were measured. RESULTS: On b = 600 seconds/mm(2) DWI, mass-forming FP was visually indistinguishable from the remaining pancreas whereas PC was hyperintense relative to the remaining pancreas. The mean ADC value of PC (1.46 +/- 0.18 mm(2)/second) was significantly lower than the remaining pancreas (2.11 +/- 0.32 x 10(-3) mm(2)/second; P < 0.0001), mass-forming FP (2.09 +/- 0.18 x 10(-3) mm(2)/second; P < 0.0001), and pancreatic gland in the control group (1.78 +/- 0.07 x 10(-3) mm(2)/second; P < 0.0005). There was no significant difference of ADC values between the mass-forming focal pancreatitis and the remaining pancreas (2.03 +/- 0.2 x 10(-3) mm(2)/second; P > 0.05). CONCLUSION: Differences on DWI may help to differentiate PC, mass-forming FP, and normal pancreas from each other.

Pancreatic function testing is best determined by the extended endoscopic collection technique.

OBJECTIVE: To evaluate whether the extended secretin-stimulated direct endoscopic pancreatic function test (ePFT) technique is superior to the rapid 15 minute secretin-stimulated ePFT in determining pancreatic exocrine function. METHODS: We conducted a retrospective study of 53 patients with chronic abdominal pain and normal pancreatic imaging. These patients had ePFT testing with the following modified endoscopic collection system. Porcine synthetic or human secretin was intravenously administered 15 minutes before endoscopic duodenal aspiration. The first 10-minute collection was performed in the third portion of the duodenum. A Liguory drainage tube was placed in the third portion of the duodenum. Two additional 10-minute-period collections were obtained via the drainage tube at 30 and 45 minutes after intravenous administration of secretin. All fluid collections were analyzed for bicarbonate (HCO3) concentration. RESULTS: Peak HCO3 concentrations at 15 minutes occurred in 62%, at 30 to 40 minutes in 23%, and at 45 to 55 minutes in 15%. Normal concentrations of HCO3 (> or =80 mEq/L) were seen in 70%, abnormal concentration in 7%, and equivocal concentrations (60-79 mEq/L) in 23% even after 55 minutes of duodenal collections. CONCLUSION: Collections beyond 15 minutes are necessary to improve accuracy of the ePFT in determining pancreatic exocrine function.