The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis.

BACKGROUND & AIMS: Both environmental factors, such as alcohol consumption and smoking, and genetic factors are strongly associated with the risk of developing chronic pancreatitis (CP). However, comprehensive understanding of their impacts on the progression of CP remains elusive. METHODS: A prospective cohort study was performed on a large cohort of CP patients with known genetic backgrounds. The cumulative incidence of pancreatic insufficiency after the onset of CP was analyzed using Kaplan-Meier survival curves. Multivariate Cox proportional hazards regression analysis also was performed. RESULTS: A total of 798 patients were enrolled in the study and followed up for 10.5 years. Rare pathogenic genotypes in the SPINK1, PRSS1, CTRC, or CFTR genes were identified in 410 (51.4%) patients. The development of pancreatic insufficiency was significantly earlier in patients with a history of smoking and/or alcohol consumption in both the positive (P < .001) and negative (P = .001) gene mutation groups. However, the development of pancreatic insufficiency did not differ significantly between patients with and without gene mutations despite alcohol and/or smoking status, with P values of .064 and .115, respectively. Multivariate Cox regression analysis showed that age at onset of CP (hazard ratio, [HR], 1.02; P < .001) and alcohol consumption (HR, 1.86; P < .001) were independent risk factors for the development of diabetes, while male sex (HR, 1.84; P = .022) and smoking (HR, 1.56; P = .028) were predictors of steatorrhea. CONCLUSIONS: Although rare pathogenic mutations in the 4 major susceptibility genes for CP were not correlated significantly with the development of pancreatic insufficiency, environmental factors (either alcohol consumption or smoking) significantly accelerated disease progression (ClinicalTrials.gov: NCT04574297).

SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort.

OBJECTIVE: The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). METHODS: This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients' demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. RESULTS: PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. CONCLUSIONS: CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.

Factors associated with prior acute pancreatitis episodes among patients with chronic pancreatitis.

BACKGROUND: The relationship between chronic pancreatitis (CP) and acute pancreatitis (AP) is complex and not well understood. CP could be preceded by antecedent episodes of AP. AIMS: The aim of this study was to explore both genetic and environmental factors associated with AP episodes before the diagnosis of CP. METHODS: This was a cross-sectional study including 1022 patients. Detailed demographic, genetic, and clinical data were collected. Based on the presence of AP episode(s) before diagnosis of CP, patients were divided into AP group (further classified into single episode of AP group and recurrent AP group) and non-AP group. Related factors among these groups were assessed using multivariate logistic regression model. RESULTS: Before diagnosis of CP, 737 patients (72.1%) had a history of AP. Smoking(P = 0.005) and heavy alcohol consumption(P = 0.002) were risk factors for AP while age at CP onset(P < 0.001), harboring the SPINK1 mutation(P < 0.001), diabetes(P < 0.001) and steatorrhea(P < 0.001) were protective factors. Further, alcoholic CP(P = 0.019) was the only independent risk factor for recurrent AP attacks while age at onset of CP(P < 0.001), pancreatic stones(P = 0.024). and pseudocysts(P = 0.018) served as protective factors. CONCLUSIONS: SPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations.

Dual-energy CT imaging of thoracic malignancies.

Computed tomography (CT) plays a pivotal role in the detection, characterization, and staging of lung cancer and other thoracic malignancies. Since the introduction of clinically viable dual-energy CT techniques, substantial evidence has accumulated on the use of this modality for imaging chest malignancies. This article describes the principles of dual-energy CT along with suitable image acquisition, reconstruction, and postprocessing strategies for oncologic applications in the chest. The potential of dual-energy CT techniques for the detection, characterization, staging, and surveillance of chest malignancy, as well as the limitations of this modality are discussed.

Automatic bone removal dual-energy CT angiography for the evaluation of intracranial aneurysms.

PURPOSE: To evaluate the diagnostic accuracy of dual-energy computed tomographic angiography (DE-CTA) in the detection of intracranial aneurysms and to determine whether DE-CTA provides adequate information to guide treatment choice. MATERIALS AND METHODS: Eighty patients (31 men and 49 women; mean [SD] ages of 52 [9] years) with spontaneous subarachnoid hemorrhage underwent DE-CTA. The performance of DE-CTA was compared with conventional CTA created from average weighted images and digital subtraction angiography (DSA). Sensitivity and specificity for aneurysm detection were determined on a per-patient and per-aneurysm basis. The treatment choice was assessed on the basis of aneurysm neck size and/or the dome/neck ratio. RESULTS: With DSA as reference standard (n = 61; 47 aneurysms in 41 patients), DE-CTA correctly detected 45 aneurysms in 41 patients corresponding to sensitivity and specificity of 100% and 95.0% on a per-patient basis versus 95.7% and 95.0% on a per-aneurysm basis, whereas conventional CTA correctly detected 43 aneurysms in 39 patients corresponding to sensitivity and specificity of 95.1% and 95.0% on a per-patient basis versus 91.5% and 95.0% on a per-aneurysm basis. No statistical difference between DE-CTA and conventional CTA was found for the diagnostic evaluation of intracranial aneurysms. Surgery was performed to treat 38 aneurysms, coiling in 26 aneurysms, stent in one patient, and follow-up in the remaining 5 aneurysms. Dual-energy CTA correctly predicted treatment choice in 44 aneurysms, with 15 aneurysms coiled and 29 aneurysms clipped. CONCLUSIONS: Compared with DSA, DE-CTA had a comparable diagnostic accuracy for the detection of intracranial aneurysms, visualization of the morphology of aneurysms at the skull base, and prediction of aneurysm treatment choice in most patients with spontaneous subarachnoid hemorrhage based on this study.

Diagnostic accuracy of dual-source CT coronary angiography: The effect of average heart rate, heart rate variability, and calcium score in a clinical perspective.

BACKGROUND: Dual-source CT coronary angiography (CTCA) has been used to detect coronary artery disease; however, the factors with potential to affect its diagnostic accuracy remain to be defined. PURPOSE: To prospectively evaluate the accuracy of dual-source CTCA in diagnosing coronary artery stenosis according to conventional coronary angiography (CAG), and the effect of average heart rate, heart rate variability, and calcium score on the accuracy of CTCA. MATERIAL AND METHODS: A total of 113 patients underwent both dual-source CTCA and CAG. The results were used to evaluate the findings in dual-source CTCA to assess the accuracy in the diagnosis of > or =50% (significant stenosis) and >75% (severe stenosis) of coronary artery according to those by CAG. Patients were divided into subgroups according to their heart rate (HR), HR variability (HRV), and calcium score, and the accuracy of CTCA was further evaluated. The chi-square test was used to analyze the difference in sensitivity and specificity for the detection of > or =50% and >75% coronary stenosis among subgroups. The generalized estimation equation method was used in per-vessel analysis to adjust for within-patient correlation. RESULTS: In all, 113 patients had 338 vessels and 1661 segments evaluated by CAG. Dual-source CTCA displayed 1527 segments (91.9%). Among them, 1468 segments (calcium score by CAG score 1, n=1018; score 2, n=270; score 3, n=180) were assessable in CTCA. On a per-patient analysis, the sensitivity and specificity of CTCA were 93.9% and 93.5% for significant stenosis and 86.9% and 98.1% for severe stenosis. On a per-vessel basis, the sensitivity and specificity were 90.2% and 97.1% for significant and 83.3% and 98.1% for severe stenosis. On a per-segment analysis, the sensitivity and specificity were 90.2% and 97.1% for significant and 83.3% and 98.1% for severe stenosis. Average HR had no effect on the sensitivity and specificity of CTCA (P>0.05); whereas HRV and calcium score had some effect on the sensitivity and specificity of CTCA (P<0.05). CONCLUSION: On a per-patient, per-vessel, and per-segment basis, dual-source CTCA has a high sensitivity and specificity for the diagnosis of coronary artery stenosis. Average HR has no effect on the diagnostic accuracy of CTCA, while HRV and calcium score have a statistically significant effect on the sensitivity and specificity of CTCA.

Liver virtual non-enhanced CT with dual-source, dual-energy CT: a preliminary study.

PURPOSE: To compare virtual non-enhanced liver CT (VNCT) from dual-energy CT (DECT) with true non-enhanced liver CT (TNCT) in patients. METHODS: A total of 102 patients underwent multi-phase abdominal CT. Liver arterial VNCT (VNCT(A)) and portovenous VNCT (VNCT(V)) images were derived from the arterial and portovenous DECT data. The mean CT number, signal to noise ratio (SNR), image quality, contrast to noise (CNR) of liver lesions, lesion detectability and radiation dose were compared. RESULTS: There was no difference in mean CT numbers of all organs (all P>0.05). SNR on VNCT images was higher than that of TNCT (all P<0.001). Image quality of VNCT was diagnostic but lower than that of TNCT (P<0.001). VNCT(A) images were superior to VNCT(V) (P<0.001). VNCT(A) and VNCT(V) detected 78 (91%) and 70 (81%) of 86 hepatic focal lesions visualised on TNCT. There was no difference in the size, attenuation and CNR of focal hepatic lesions (all P>0.05), but SNR of the lesions on VNCT was higher than that on TNCT (P<0.001). Radiation dose of biphase DECT was lower than that of routine triphase CT (P<0.001). CONCLUSION: VNCT(A) may potentially replace TNCT as part of a multi-phase liver imaging protocol with consequent saving in radiation dose.

Dual source dual-energy computed tomography of acute myocardial infarction: correlation with histopathologic findings in a canine model.

PURPOSE: To evaluate the feasibility and value of dual-energy computed tomography myocardial iodine maps in the diagnosis of acute myocardial infarction. MATERIALS AND METHODS: In 6 dogs, arterial-phase myocardial dual-energy computed tomography imaging were performed 1 day prior to and 3 hours after the surgical ligation of the left anterior descending artery to generate 100 kVp, 140 kVp, average weighted images, and dual energy myocardial iodine maps. For each of the 17 segments of the left ventricle (LV, 102 total segments), the presence or absence myocardial infarction was determined by histopathology and correlated to blinded reader determination of infarcted and noninfarcted myocardium at computed tomography (CT). Statistical analysis for diagnostic accuracy of aforementioned techniques and inter-reader agreement was performed. RESULTS: The LV myocardial contrast enhancement at the average weighted images and iodine maps were uniform in all 6 dogs before surgery. Following anterior descending artery ligation, histopathology showed 40 infarcted left ventricular segments and 62 noninfarcted segments. For the postligation CT scans, 100 kVp, 140 kVp, average weighted images, and myocardial iodine maps showed 33, 28, 33, 34 infarcted segments and 53, 56, 56, 52 noninfarcted segments for both readers; corresponding to per-segment sensitivities of 83%, 70%, 80%, 92% and specificities of 85%, 90%, 92%, 80% for detecting myocardial infarction. No statistical difference was found for diagnostic accuracy of 100 kV, 140 kV, weighted average images, and iodine maps to detect myocardial infarct segments (all P > 0.05 for both readers). Good inter-reader agreement was seen for myocardial infarct detection using iodine maps (kappa = 0.80). CONCLUSIONS: Myocardial single- and dual-energy CT imaging shows high per-segment sensitivity and moderate specificity for detecting acute myocardial infarction in a canine model with histopathology as the standard of reference.

Dual-energy CT angiography in the evaluation of intracranial aneurysms: image quality, radiation dose, and comparison with 3D rotational digital subtraction angiography.

OBJECTIVE: The purpose of this study was to evaluate the image quality, radiation dose, and diagnostic accuracy of dual-energy CT angiography (CTA) compared with 3D rotational digital subtraction angiography (DSA) in the detection of intracranial aneurysms. SUBJECTS AND METHODS: Forty-six patients with clinically suspected intracranial aneurysms underwent dual-source dual-energy CTA and 3D DSA. For the analysis of the image quality and radiation dose of dual-energy CTA, 46 patients who underwent digital subtraction CTA were recruited as a control group. The image quality of dual-energy CTA and digital subtraction CTA was rated on a 4-point scale as excellent, good, moderate, or poor. The radiation dose of CTA was recorded according to patient protocol. Aneurysm detection with dual-energy CTA compared with 3D DSA was analyzed on a per-patient and on a peraneurysm basis. Sensitivity, specificity, and positive and negative predictive values for aneurysm presence were determined. The mean maximum diameter and dome and neck dimensions of aneurysms were measured on dual-energy CTA and 3D DSA images. Correlation analysis between the two techniques was performed. RESULTS: There was no statistical difference between the image quality of dual-energy CTA and that of digital subtraction CTA (p>0.05). Patients undergoing dual-energy CTA received a smaller radiation dose (volume CT dose index, 20.6+/-0.1 mGy [mean+/-SD]; dose-length product, 398.6+/-19.0 mGy x cm) than those undergoing digital subtraction CTA (volume CT dose index, 50.4+/-3.4 mGy; dose-length product, 1,095.6+/-114.2 mGyxcm) (p<0.05). Three-dimensional DSA showed no aneurysm in 11 patients and 40 aneurysms in 35 patients. The mean maximum diameter of the aneurysms was 6+/-3 mm; the dome measurement, 5+/-3 mm; and the neck dimension, 3+/-2 mm. With dual-energy CTA, 38 aneurysms in 34 patients were correctly detected, and two aneurysms in two patients were missed. With DSA as the standard of reference, the sensitivity, specificity, and positive and negative predictive values of dual-energy CTA in the detection of intracranial aneurysm were 97.1%, 100%, 100%, and 91.7% on a per-patient basis and 95.0%, 100%, 100%, and 99.7% on a per-aneurysm basis. Dual-energy CTA had sensitivities of 93.8%, 100%, and 80.0% and specificities of 100%, 100%, and 100% in the detection of aneurysms larger than 5 mm, those measuring 3.1-5 mm, and aneurysms 3 mm or smaller. At dual-energy CTA, the mean maximum diameter and dome and neck dimensions were 6+/-3 mm, 5+/-3 mm, and 3+/-2 mm. Excellent correlation was found between DSA and dual-energy CTA findings with respect to mean maximum diameter and dome and neck dimensions (r=0.969, 0.957, and 0.870; p = 0.000). CONCLUSION: On the basis of the findings in the small series of patients evaluated, contrast-enhanced dual-energy CTA had diagnostic image quality at a lower radiation dose than digital subtraction CTA and high diagnostic accuracy compared with 3D DSA in the detection of intracranial aneurysms.