Samer Alkaade

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

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.

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.

Suspected chronic pancreatitis with normal MRCP: Findings on MRI in correlation with secretin MRCP

To review pancreatic MRI findings and their relationship with estimated pancreatic exocrine function on secretin‐stimulated MR cholangiopancreatography (S‐MRCP) in patients with clinically suspected chronic pancreatitis and normal baseline MRCP findings.

Physical and mental quality of life in chronic pancreatitis: a case-control study from the North American Pancreatitis Study 2 cohort.

Objectives The objective of this study was to define the quality of life (QOL) in patients with chronic pancreatitis (CP). Methods We studied 443 well-phenotyped CP subjects and 611 control subjects prospectively enrolled from 20 US centers between 2000 and 2006 in the North American Pancreatitis Study 2. Responses to the SF-12 questionnaire were used to calculate the mental (MCS) and physical component summary scores (PCS) with norm-based scoring (normal ≥50). Quality of life in CP subjects was compared with control subjects after controlling for demographic factors, drinking history, smoking, and medical conditions. Quality of life in CP was also compared with known scores for several chronic conditions. Results Both PCS (38 [SD, 11.5] vs 52 [SD, 9.4]) and MCS (44 [SD, 11.5] vs 51 [SD, 9.2]) were significantly lower in CP compared with control subjects (P < 0.001). On multivariable analyses, compared with control subjects, a profound decrease in physical QOL (PCS 12.02 points lower) and a clinically significant decrease in mental QOL (MCS 4.24 points lower) was seen due to CP. Quality of life in CP was similar to (heart, kidney, liver, lung disease) or worse than (nonskin cancers, diabetes mellitus, hypertension, rheumatoid arthritis) other chronic conditions. Conclusions The impact of CP on QOL appears substantial. The QOL in CP subjects appears to be worse or similar to the QOL of many other chronic conditions.

MRI and S‐MRCP findings in patients with suspected chronic pancreatitis: Correlation with endoscopic pancreatic function testing (ePFT)

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).

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.

Hepatobiliary and Pancreatic MRI and MRCP Findings in Patients with HIV Infection

OBJECTIVE The purpose of this article is to describe the spectrum of MRI and MR cholangiopancreatography (MRCP) findings of hepatic, pancreatic, and biliary manifestations in patients with HIV infection. CONCLUSION The spectrum of MRI and MRCP findings in HIV-infected patients includes acute or chronic hepatitis (or both), pancreatitis, cholangitis, acalculous cholecystitis, and biliary strictures that may resemble primary sclerosing cholangitis. The presence of segmental extrahepatic biliary strictures is characteristic of AIDS cholangiopathy.

Focal pancreatitis mimicking pancreatic mass: magnetic resonance imaging (mri)/magnetic resonance cholangiopancreatography (mrcp) findings including diffusion-weighted mri:

Background: Focal pancreatitis (FP) is a confined inflammation that mimics a pancreatic mass. Its imaging diagnosis is important to avoid unnecessary procedures. Purpose: To describe the spectrum of magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and diffusion-weighted MRI (DWI) findings of focal pancreatitis mimicking pancreatic masses. Material and Methods: Findings of MRI/MRCP including DWI with a b value of 0 and 600 s/mm2 in 14 patients with pancreatic masses on MRI were retrospectively reviewed and compared to normal pancreas in 14 patients as a control group. Results: FP revealed hypointense signal intensity (SI) (3/14), hypo- to isointense SI (7/14), or isointense SI (4/14) on T1-weighted images, and hypointense SI (1/14), isointense SI (5/14), iso- to hyperintense SI (7/14), or hyperintense SI (1/14) on T2-weighted images compared to remaining pancreas (RP). MRCP images revealed dilatation of the common bile duct (CBD) and main pancreatic duct (MPD) (5/14), dilatation of the MPD only (3/14), dilatation of the CBD only (3/14), and normal MPD and CBD (3/14). Both FP and RP revealed three types of time–signal intensity curves: 1) rapid rise to a peak, with a rapid decline (FP=2, RP=4), 2) slow rise to a peak, followed by a slow decline (FP=5, RP=4), and 3) slower rise to a peak, with a slow decline or plateau (FP=7, RP=6). Mean apparent diffusion coefficient (ADC) values for FP and RP were 2.09±0.18 and 2.03±0.2×10−3 mm2/s, respectively. ADC values of FP and RP revealed no significant difference. Conclusion: The spectrum of imaging findings of focal pancreatitis on MRI/MRCP including DWI was described. Findings of FP were not distinctive as compared to the remaining pancreas.

Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States

Aliment Pharmacol Ther 2011; 33: 149–159

Normal Pancreatic Exocrine Function Does Not Exclude MRI/MRCP Chronic Pancreatitis Findings

Objective Abnormal pancreatic function tests have been reported to precede the imaging findings of chronic pancreatitis. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is increasingly accepted as the primary imaging modality for the detection of structural changes of early mild chronic pancreatitis. The aim of this study was to evaluate MRI/MRCP findings in patients with symptoms consistent with chronic pancreatitis who have normal Secretin Endoscopic Pancreatic Function test. Methods A retrospective study of 32 patients referred for evaluation of chronic abdominal pain consistent with chronic pancreatitis and reported normal standard abdominal imaging (ultrasound, computed tomography, or MRI). All patients underwent Secretin Endoscopic Pancreatic Function testing and pancreatic MRI/MRCP at our institution. We reviewed the MRI/MRCP images in patients who had normal Secretin Endoscopic Pancreatic Function testing. MRI/MRCP images were assessed for pancreatic duct morphology, gland size, parenchymal signal and morphology, and arterial contrast enhancement. Results Of the 32 patients, 23 had normal Secretin Endoscopic Pancreatic Function testing, and 8 of them had mild to marked spectrum of abnormal MRI/MRCP findings that were predominantly focal. Frequencies of the findings were as follows: pancreatic duct stricture (n=3), pancreatic duct dilatation (n=3), side branch ectasia (n=4), atrophy (n=5), decreased arterial enhancement (n=5), decreased parenchymal signal (n=1), and cavity formation (n=1). The remaining15 patients had normal pancreatic structure on MRI/MRCP. Conclusions Normal pancreatic function testing cannot exclude abnormal MRI/MRCP especially focal findings of chronic pancreatitis. Further studies needed to verify significance of these findings and establish MRI/MRCP imaging criteria for the diagnosis of chronic pancreatitis.