Presence Of Chronic Pancreatitis Research Articles

Female-specific pancreatic cancer survival from CT imaging of visceral fat implicates glutathione metabolism in solid tumors

To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p=0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p=0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion.

Diagnostic Yield of Repeat Endoscopic Ultrasound-Guided Fine Needle Biopsy for Solid Pancreatic Lesions.

we performed a retrospective case-control study, including cases with repeat EUS FNB for a solid pancreatic lesion, matched on a 1:2 ratio on age, sex, tumor location and presence of chronic pancreatitis with cases diagnosed on the first EUS FNB. thirty-four cases and 68 controls were included in the analysis. Diagnostic accuracies were 80% and 88% in the repeat and single EUS FNB groups, respectively (p = 0.824). The second EUS FNB had a sensitivity of 80%, a specificity of 75%, a positive predictive value of 96%, and a negative predictive value of 33%. Of the 34 patients in the repeat EUS FNB group, 25 (74%) had a positive diagnosis with the second EUS FNB, 4 (12%) after surgery due to a second negative EUS FNB, 4 (12%) during clinical follow-up, and 1 (3%) after a third EUS FNB. Of the 25 patients diagnosed on the repeat EUS FNB, 17 (68%) had pancreatic adenocarcinomas, 2 (8%) neuroendocrine tumors, 2 (8%) other autoimmune pancreatitis, 2 (8%) chronic pancreatitis nodules, 1 (4%) renal cancer metastasis, and 1 (4%) other malignant diagnostic. There were no complications reported after the second EUS FNB in this study. repeat EUS FNB made a diagnosis in three fourths of patients with solid pancreatic lesions and a first negative EUS FNB, with 26% of benign lesions. This supports the repetition of EUS FNB sampling in this clinical situation.

Ефективність корекції маси тіла як частини реабілітаційних заходів у хворих на цукровий діабет 2 типу, поєднаний з ожирінням та хронічним панкреатитом

The purpose of the study was to analyze the impact of a physical exercise program and therapeutic massage as a part of rehabilitation program in patients with type 2 diabetes mellitus combined with obesity and chronic pancreatitis on carbohydrate metabolism. Materials and methods. 579 patients with type 2 diabetes mellitus with overweight / obesity and concomitant chronic pancreatitis were included in the study. According to the analysis of the medical case histories, patients took metformin in the minimum dose that ensured the effectiveness and maximum tolerability of the drug, which was 1500-2000 mg/day. Combined therapy, which was taken by some patients, included: metformin and sulfonylurea derivatives in effective therapeutic doses. Against the background of the prescribed therapy, in the post-hospital period, rehabilitation programs were offered, which included a program of physical exercises and therapeutic massage, during 1 month. Results and discussion. It is likely that patients with type 2 diabetes mellitus, regardless of body mass index and the presence of chronic pancreatitis, received combined therapy. At the same time, the largest percentage of patients on combined therapy was recorded with type 2 diabetes mellitus and chronic pancreatitis. Both the use of metformin in the form of monotherapy and the use of combined therapy (metformin and gliclazide) in the condition of patients only with type 2 diabetes mellitus and with a comorbid type 2 diabetes mellitus with chronic pancreatitis and increased body weight / obesity do not allow reaching the target levels of glucose and HbA1c. It was established that the number of patients with type 2 diabetes mellitus without comorbidity who received mono- and combined therapy in combination with a complex of rehabilitation measures reached the target HbA1c indicators. It is also worth noting the increase in the number of insufficiency with type 2 diabetes mellitus combined with overweight / obesity and chronic pancreatitis, indicating the effectiveness of the proposed rehabilitation measures. Conclusion. The additional appointment in the post-hospital period of a complex of rehabilitation program, which includes physical exercises and therapeutic massage, contributed to the achievement of the target level of HbA1c in type 2 diabetes mellitus without comorbidity in 72.73% of patients with monotherapy and in 63.41% with combined therapy and with the associated course of diabetes mellitus, overweight / obesity and pancreatitis, respectively, in 37.62% and 38.28%

THE STATE OF ELASTIC PROPERTIES OF ARTERIES IN PATIENTS WITH CHRONIC PANCREATITIS IN COMBINATION WITH ARTERIAL HYPERTENSION

Objective: Arterial stiffness is considered to be an independent predictor of cardiovascular events. Factors associated with increased arterial stiffness in patients with hypertension continue to be actively studied. The aim of this study was to determine whether the presence of chronic pancreatitis is associated with arterial stiffness in patients with hypertension. Design and method: 110 patients aged 45–65 years with chronic pancreatitis were examined. The first group consisted of patients with a combined course of chronic pancreatitis with arterial hypertension; the second group - patients with chronic pancreatitis without concomitant hypertension. All patients were examined for blood lipids. Arterial stiffness was determined by the pulse wave velocity. Results: The level of brachial artery augmentation index was significantly lower by 43% in patients with chronic pancreatitis in combination with arterial hypertension, while the aortic augmentation index was significantly higher by 37.6% (p < 0.01). It was found that patients of the 1st group had a significantly higher pulse wave velocity in the carotid-femoral segment in comparison with 2nd group - 9.3 [8.5;9.7] and 8.6 [8.1;8.9] respectively (p < 0.01). Significant correlations have been established between the brachial artery augmentation index and age, total cholesterol, atherogenic ratio, high and low density lipoprotein cholesterol, triglycerides, cardiovascular risk level by the SCORE scale – r = 0.39; p < 0.01; r = 0.31; p < 0.01 r = 0.34; p < 0.01; r = 0.36; p < 0.01; r = 0.42; p < 0.01; r = 0.43; p < 0.01; r = 0.36; p < 0.01 respectively. Conclusions: The presence of chronic panreatitis is associated with increased arterial stiffness in patients with hypertension.

Application of artificial intelligence in diagnosis of pancreatic malignancies by endoscopic ultrasound: a systemic review.

Background:Pancreatic cancer (PC) is a highly fatal malignancy with a global overall 5-year survival of under 10%. Screening of PC is not recommended outside of clinical trials. Endoscopic ultrasonography (EUS) is a very sensitive test to identify PC but lacks specificity and is operator-dependent, especially in the presence of chronic pancreatitis (CP). Artificial Intelligence (AI) is a growing field with a wide range of applications to augment the currently available modalities. This study was undertaken to study the effectiveness of AI with EUS in the diagnosis of PC.Methods:Studies from MEDLINE and EMBASE databases reporting the AI performance applied to EUS imaging for recognizing PC. Data were analyzed using descriptive statistics. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of the included studies.Results:A total of 11 articles reported the role of EUS in the diagnosis of PC. The overall accuracy, sensitivity, and specificity of AI in recognizing PC were 80–97.5%, 83–100%, and 50–99%, respectively, with corresponding positive predictive value (PPV) and negative predictive value (NPV) of 75–99% and 57–100%, respectively. Types of AI studied were artificial neural networks (ANNs), convolutional neural networks (CNN), and support vector machine (SVM). Seven studies using other than basic ANN reported a sensitivity and specificity of 88–96% and 83–94% to differentiate PC from CP. Two studies using SVM reported a 94–96% sensitivity, 93%–99% specificity, and 94–98% accuracy to diagnose PC from CP. The reported sensitivity and specificity of detection of malignant from benign Intraductal Papillary Mucinous Neoplasms (IPMNs) was 96% and 92%, respectively.Conclusion:AI reported a high sensitivity with high specificity and accuracy to diagnose PC, differentiate PC from CP, and differentiate benign from malignant IPMN when used with EUS.

ОСОБЕННОСТИ КЛИНИКО-ЛАБОРАТОРНЫХ ПОКАЗАТЕЛЕЙ У ПАЦИЕНТОВ С РЕЦИДИВИРУЮЩИМИ АФТАМИ ПОЛОСТИ РТА НА ФОНЕ КИСЛОТОЗАВИСИМЫХ ЗАБОЛЕВАНИЙ ЖЕЛУДОЧНО-КИШЕЧНОГО ТРАКТА

Subject. Some features of the clinical picture, hygienic and microbiological state of the oral cavity, acidity and free-radical oxidation of the oral fluid in patients with recurrent aphthates on the background of acid-dependent diseases of the gastrointestinal tract are considered.
 The aim is to assess the relationship between clinical and laboratory parameters in patients with recurrent oral aphthae associated with acid-dependent diseases of the gastrointestinal tract.
 Methodology. A comprehensive clinical and laboratory examination of 58 young people with revealed recurrent aphthae of the oral cavity against the background of acid-dependent diseases of the gastrointestinal tract was carried out. The level of oral hygiene was assessed using the ONI-s index, the state of free-radical oxidation of the oral fluid - the "Chemilumimer-003" device, individual representatives of the normal flora were identified by inoculating the contents from the surface of aphthous elements on special differential diagnostic media of the HiCrome series. The acidity of the oral fluid was determined using a universal indicator litmus paper pH-1-14, short-term intragastric pHmetry was performed directly during fibrogastroduodenoscopy.
 Results. In 46.4 % of those examined, recurrent aphthae were found on the oral mucosa. In persons with chronic gastritis and duodenitis, the frequency of recurrences once a year was 37.9 %, 2-3 times a year ― 62.0, with the presence of chronic pancreatitis against the background of hyperacid gastric secretion ― 44.8 and 55.2, respectively. In patients with recurrent aphthae, a low level of oral hygiene, a violation of its microbiome, and a change in the acidity of the oral fluid were revealed.
 Conclusions. The presence of recurrent aphthae complicates individual oral hygiene, because accompanied by severe pain and paresthetic symptoms. This is manifested by an increase in the ONI-S index and a disturbance in the state of the normobiome in the form of an increase in the growth of resident microflora against the background of changes in the acidity of the oral fluid. Chemiluminescence indices correlate with the hygienic state of the oral cavity, qualitative changes in the normobiota and pH of the oral fluid in the studied clinical groups.

Construction of nomogram to predict postoperative pancreatic fistula after distal pancreatectomy utilizing the ACS-NSQIP pancreatectomy targeted database

Presenter: Jonathan Pastrana Del Valle MD | Beth Israel Deaconess Medical Center Background: Distal pancreatectomy is widely employed in the treatment of benign and malignant conditions of the body and tail of the pancreas. Postoperative pancreatic fistula is a frequent and potentially morbid complication after this operation, occurring in up to 20% of distal pancreatectomy patients. Effective methods for predicting and preventing postoperative pancreatic fistula are still sought. While effective risk assessment models have been developed for postoperative pancreatic fistula after pancreaticoduodenectomy, to our knowledge, a similar model for distal pancreatectomy does not exist. The aim of this study was to investigate factors associated with postoperative pancreatic fistula following distal pancreatectomy and to create a risk model to predict this complication using data from the ACS-NSQIP database. Methods: Patients who underwent distal pancreatectomy from 2014 to 2017 were selected from the ACS-NSQIP pancreatectomy targeted database. Clinically relevant (grade B or C) fistulas were identified using the 2016 ISGPS definitions. We utilized chi square tests on categorical variables and logistic regression on continuous variables to assess associations of preoperative and intraoperative variables with postoperative fistula. Variables with a p<0.10 on univariable analysis were then included in a multivariable logistic regression model, and a nomogram was constructed from this model. The predictive ability of the nomogram was assessed using the concordance statistic (c-statistic), and its calibration was tested using the Hosmer-Lemeshow test. Results: A total of 7,088 patients who underwent distal pancreatectomy from 2014 to 2017 were identified in the ACS-NSIQP database. Clinically relevant postoperative pancreatic fistula were identified in 1,174 (16.6%) of the patients. Univariable analysis identified male sex, higher BMI, smoking history, congestive heart failure, disseminated cancer, low pre-operative albumin, chemotherapy within 90 days of surgery, radiation within 90 days of surgery, intra-operative drain placement, vascular resection, and histology were associated with pancreatic fistula (all p<0.05). Gland texture, pancreatic duct size, and presence of chronic pancreatitis were not significantly associated with fistula. Variables independently associated with pancreatic fistula in the multivariable model were male sex, higher BMI, smoking history, congestive heart failure, higher preoperative platelet count, intraoperative drain placement, vascular resection, and histology (all p<0.01). The nomogram constructed from this analysis is shown in panel A. The concordance statistic of the nomogram is 0.625 (ROC curve shown in panel B). The nomogram appeared well calibrated (panel C) with a Hosmer-Lemeshow p=0.723 consistent with a good fit. Conclusion: Male sex, higher BMI, smoking history, congestive heart failure, higher pre-operative platelet count, intra-operative drain placement, vascular resection, and histology are independently associated with risk of developing postoperative pancreatic fistula after distal pancreatectomy. A nomogram based on these risk factors yielded a c- statistic of 0.625 suggesting that other variables not accounted for may contribute to the risk of pancreatic fistula and/or there is some inherent unpredictability in the development of this complication. The nomogram does provide a well calibrated prediction of risk based on easily determined pre-operative and intra-operative variables, and thus may be useful in post-operative management. Further study to externally validate this nomogram is warranted.

Эндоваскулярная эмболизация гастродуоденальной артерии при её панкреатогенной аррозии: клинический случай

Arrosion of the peripancreatic vascular structures is a rare, but life-threatening condition and requires surgical treatment. One of the most common causes of arrosia is the presence of pancreatic pseudocyst. Imaging methods play a crucial role not only in terms of identifying the described pathology, but also in planning the tactics of surgical treatment. We present a clinical case of a patient, a 44-year-old male, with pseudocyst in the pancreatic head in the presence of chronic pancreatitis, complicated by bleeding into its cavity as a result of an arrosion of the gastroduodenal artery, which required endovascular embolization and drainage of the pseudocyst. This clinical case shows the possibility of endovascular embolization of the injured gastroduodenal artery with microspirals.

Ефективність лікування хворого на вперше діагностований туберкульоз легень із супутньою патологією в залежності від способу введення антимікобактеріальних препаратів

Resume. The use of antimycobacterial therapy in its majority leads to a positive dynamics of the TB disease, smear and sputum cultures conversion and cure of the patient. The lack of an expected positive response to the therapy happens in a limited number of patients. One of the most common reason for the lack of a positive response, in the conditions of the appointment of therapeutic agents in accordance with the identified sensitivity and controlled use of chemotherapy, may be the presence of concomitant pathology and malabsorption / maldigestia syndrome. Your attention is given to the clinical case of the progression of pulmonary tuberculosis on the background of oral administration of antimycobacterial drugs. During the treatment, the presence of chronic pancreatitis and malabsorption syndrome of oral forms of drugs was confirmed, which allowed changing the treatment tactics and reaching the patient's cure.

Predictors for Pancreatic Cancer Diagnosis Following New-Onset Diabetes Mellitus.

Objectives:New-onset diabetes mellitus (NODM) in adults is often an early manifestation of pancreatic cancer (PaCa), but the incidence of PaCa in this cohort is rather low. We evaluated whether combining other patient factors such as age, smoking history, the absence of obesity, the presence of chronic pancreatitis (CP), and gallstone disease can result in a more enriched cohort.Methods:After a washout period of 2 years to exclude pre-existing PaCa or DM, 507,378 non-diabetic patients in the veterans' administration healthcare system were identified. Patients <40 years (n=54,465) and those with PaCa diagnosed before the diagnosis of diabetes (n=22) were excluded. A total of 452,804 veterans were followed for development of DM or PaCa.Results:73,811 patients (16.3%) developed NODM during the follow-up period. One hundred and eighty-three NODM patients (0.25%) were diagnosed with PaCa within 3 years. In comparison, 434 of 378,993 remaining patients (0.11%) developed PaCa in 3 years following inclusion into the study [relative risk (RR)=2.27, 95% confidence intervals (CI) 1.96, 2.63; P<0.0001]. The risk of PaCa diagnosis was higher among patients who were non-obese (RR=1.51), were ≥65 years old (RR=2.01), were heavy smokers (RR=1.55), and had a history of CP (RR=4.72) or gallstone disease (RR=2.02). Using a combination of these risk factors in NODM patients resulted in up to 0.72% three-year risk of PaCa but captured only 17% of patients with PaCa.Conclusions:Based on our findings, the likelihood of PaCa in adults with NODM even after adjusting for other potential risk factors for PaCa including age, body mass index, smoking, gallstones, and CP is probably not high enough to recommend routine evaluation for all these patients for underlying PaCa.

Squamoid Cystosis of Pancreatic Ducts: A Variant of a Newly-Described Cystic Lesion, with Evidence for an Obstructive Etiology

We describe a 40-year-old man who was found to have a cystic mass in the pancreatic tail during workup for weight loss and abdominal discomfort. Although computed tomography scan showed a single cyst associated with dilatation of the main pancreatic duct, gross and histologic examination of the distal pancreatectomy specimen actually revealed a central cyst that was surrounded by multiple smaller cystic spaces. This distinctive appearance was formed from extensive cystic dilatation and squamous metaplasia of the native pancreatic duct system. Further, a traumatic neuroma was discovered near the junction between normal and abnormal parenchyma. We believe that this case represents a variant of the newly-described squamoid cyst of pancreatic ducts which we term squamoid cystosis of pancreatic ducts. The presence of chronic pancreatitis and a traumatic neuroma supports the hypothesis that squamoid cysts are non-neoplastic lesions arising from prior duct obstruction.

Follow up of Branch Duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN) of the pancreas with a cyst over 30mm in diameter: A single center experience

s / Pancreatology Aims: The aim of our study was to examine independent factors (gender, presence of chronic pancreatitis, anatomic localization, mucin expression) as potential risk factors for malignant IPMTs. Patients & methods: 48 patients underwent surgical resection were proved to have IPMT between the period of 2002-2013. Samples were grouped according to type of the tumour as main duct-(MD), branch duct(BD) or mixed-type (MX) IPMTs. We created subgroups based on the malignant behaviour and the mucin expression profile, like intestinal (I), pancreatobiliary (PB) and gastric-type (G) IPMTs. We examined the presence of chronic pancreatitis and the correlation with the presence of malignant IPMTs. Results: 12 BD-,15MDand 21MXtype IPMTswere found.16,7% of the patients had low-gradeand 33,3% had high-grade dysplasia. Based on the mucin expression profile 14,2% of the G-, 37,5% of the Iand 75% of the PBtype IPMTs were found to be malignant. 79,2% of the malignant IPMTs, were localized in the head of the pancreas. 33,3% of the patients without chronic pancreatitis, while 66,7% of the patients with chronic pancreatitis had malignant IPMT. Conclusion: The presence of chronic pancreatitis may have an important role to increase the malignant behaviour of the IPMTs. Lack of MUC1 expression may be related to less invasive characteristics of IPMTs. MUC2+ alone, or MUC1+ and MUC5AC+ expression together can predict the malignant potential of IPMTs.

Clinical significance of extrapancreatic primary cancers in patients with IPMN.- An analysis of experiences in a single Japanese center-

s / Pancreatology Aims: The aim of our study was to examine independent factors (gender, presence of chronic pancreatitis, anatomic localization, mucin expression) as potential risk factors for malignant IPMTs. Patients & methods: 48 patients underwent surgical resection were proved to have IPMT between the period of 2002-2013. Samples were grouped according to type of the tumour as main duct-(MD), branch duct(BD) or mixed-type (MX) IPMTs. We created subgroups based on the malignant behaviour and the mucin expression profile, like intestinal (I), pancreatobiliary (PB) and gastric-type (G) IPMTs. We examined the presence of chronic pancreatitis and the correlation with the presence of malignant IPMTs. Results: 12 BD-,15MDand 21MXtype IPMTswere found.16,7% of the patients had low-gradeand 33,3% had high-grade dysplasia. Based on the mucin expression profile 14,2% of the G-, 37,5% of the Iand 75% of the PBtype IPMTs were found to be malignant. 79,2% of the malignant IPMTs, were localized in the head of the pancreas. 33,3% of the patients without chronic pancreatitis, while 66,7% of the patients with chronic pancreatitis had malignant IPMT. Conclusion: The presence of chronic pancreatitis may have an important role to increase the malignant behaviour of the IPMTs. Lack of MUC1 expression may be related to less invasive characteristics of IPMTs. MUC2+ alone, or MUC1+ and MUC5AC+ expression together can predict the malignant potential of IPMTs.

Characteristic of the intraductal papillary mucinous tumours (IPMTs) of the pancreas and correlation between the presence of chronic pancreatitis and the malignant potential

Conclusion The presence of chronic pancreatitis may have an important role to increase the malignant behavior of the IPMTs. Lack of MUC1 expression may be related to less invasive characteristics of IPMTs. MUC2+ alone, or MUC1+ and MUC5AC+ expression together can predict the malignant potential of IPMTs. Pathology IPMT is characterized by dilated pancreatic ducts and ductules that are lined by tall columnar mucin-producing neoplastic epithelial cells with collections of mucin within the ducts oozing from the papilla of Vater. They are classified as low-grade, high-grade or invasive tumours. Based on distribution of the tumour, IPMT is strictly classified into three clinically distinct subtypes, the main ductand branch duct-type, and from the combination of these the mixed-type.

Applications of endoscopic ultrasound in pancreatic cancer.

Since the introduction of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA), EUS has assumed a growing role in the diagnosis and management of pancreatic ductal adenocarcinoma (PDAC). The objective of this review is to discuss the various applications of EUS and EUS-FNA in PDAC. Initially, its use for detection, diagnosis and staging will be described. EUS and EUS-FNA are highly accurate modalities for detection and diagnosis of PDAC, this high accuracy, however, is decreased in specific situations particularly in the presence of chronic pancreatitis. Novel techniques such as contrast-enhanced EUS, elastography and analysis of DNA markers such as k-ras mutation analysis in FNA samples are in progress and might improve the accuracy of EUS in the detection of PDAC in this setting and will be addressed. EUS and EUS-FNA have recently evolved from a diagnostic to a therapeutic technique in the management of PDAC. Significant developments in therapeutic EUS have occurred including advances in celiac plexus interventions with direct injection of ganglia and improved pain control, EUS-guided fiducial and brachytherapy seed placement, fine-needle injection of intra-tumoral agents and advances in EUS-guided biliary drainage. The future role of EUS and EUS in management of PDAC is still emerging.

Impact of Chronic Pancreatitis on Pancreatic Resections for Malignancy

Background: Chronic pancreatitis has been shown to have potential benefit in pancreatic resections by reducing postoperative pancreatic fistula. We sought to investigate the impact of chronic pancreatitis on oncologic surgical outcomes. Materials and Methods: Consecutive partial pancreatectomies performed for malignant disease from 2005-2011 were reviewed. Patients were divided for analysis based on the presence of chronic pancreatitis. The primary outcome measures were need for intraoperative re-excision of margins and final margin status. Secondary outcome measures included pancreatic fistula rate and overall morbidity which were graded in standardized fashion. Significance was assessed for p<0.05. Results: One hundred fifty-four patients met criteria for study, 48 of which had chronic pancreatitis. Demographics, co-morbidities, diagnoses, and surgical technique were equivalent between groups. Though there was a trend towards increased re-excision of margins in the chronic pancreatitis group (p<0.08), there were no significant differences in any surgical outcome measures between groups including final margin status, pancreatic fistula rate, and overall morbidity. Multivariate analysis failed to identify chronic pancreatitis as a predictive factor for any of the chosen outcome variables. Conclusion: Despite potential for difficult dissection due to inflammatory changes in chronic pancreatitis, we found no differences in oncologic outcomes in patients undergoing pancreatectomy.

Pancreas mobile

Up to now, little is known about the mobility of the pancreas due to changes in posture. The present study was conducted to assess the position of the pancreas in the left recumbent posture (endoscopy posture), the pancreatic mobility during changes of the posture from supine to endoscopy posture and also evaluates the possible factors associated with pancreatic mobility. 199 patients with (68) or without chronic pancreatitis were examined using conventional gray-scale transabdominal ultrasound to image the position and mobility of the pancreatic head with reference to the vertebral spine and aorta in the supine and left recumbent position. In a subgroup of 75 consecutive healthy subjects regarding the pancreas, the exact moving distance of the central line of the pancreatic head from the supine to left recumbent position was obtained regarding the central line of the spine as the reference. Besides the 199 patients, 50 patients without pancreatic pathology were evaluated by endoscopic ultrasound with radial transducers. On conventional ultrasound in supine (left lateral) position the percentage of patients with right-aortal, pre-aortal, left-aortal pancreatic head were 91.0 % (49 %), 8.0 % (31 %) and 1.0 % (20 %), respectively. Significant movement of the pancreatic head in relation to the aorta was observed in 48 % of patients. The moving distance was correlated to the age, sex and the presence of chronic pancreatitis. Pancreas mobility was more pronounced in young healthy females. No association was found between the moving distance and the body mass index (BMI) and splenic size. On endoscopic ultrasound, the orientation of the pancreas with a view of more (or equal) than 180o was observed in 48 % and less than 180o in 52 % of patients. Pancreas mobile is a common phenomenon (about 50 %) which has not often been recognized in daily routine. This phenomenon is more likely in healthy young females. This knowledge might be of importance for improved interpretation of endoscopic ultrasound imaging examinations in patients with and without peripancreatic infiltration.

197 Computer-Aided Analysis of Endoscopic Ultrasonography (EUS) Images in Differentiation of Pancreatic Cancer From Chronic Pancreatitis

Endoscopic ultrasound (EUS) has the unique ability to obtain specimens for cytological analysis, thus play a key role in the diagnosis of pancreatic disease especially in evaluation patients with inconclusive findings. However, the diagnostic yields of EUS guided fine needle aspiration (FNA) for pancreatic cancer (PC) decreased in the presence of chronic pancreatitis (CP) because tumour and inflammation could have some changes similar in appearance. Therefore, distinguishing pancreatic cancer from chronic pancreatitis is a clinical challenge with current imaging agents.

Abstract 2867: TH17 cells promote early pancreatic tumorigenesis.

Abstract Chronic pancreatitis increases by 16 fold the risk of developing pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human cancers. Activating Kras mutations have been detected in 30% of early pancreatic intraepithelial neoplasias (PanINs), increasing to 100% in advanced pancreatic ductal adenocarcinoma (PDAC). We hypothesize that inflammatory cells recruited to the pancreas in response to chronic injury can interact with epithelial cells harboring activated KrasG12D and affect the progression of PanIN lesions. To test this hypothesis, we have used the inducible transgenic Mist1:CreERT2; LSL-KrasG12D (KCiMist1) adult mice in which the LSL KrasG12D allele is activated specifically in the acinar compartment. This model leads to rapid formation of PanINs with a classic "ductal" phenotype and the progression of lesions is further accelerated with the induction of chronic pancreatitis (CP) generated by recurrent injections of cerulein. We have found that TH17 cells, a subtype of CD4+ T-helper cells known to play an active role in other models of inflammation- induced tumorigenesis, are recruited to the pancreas during chronic pancreatitis and further increased upon KrasG12D activation. The differentiation of CD4+T cells into TH17 requires IL-6 and TGF-B, factors that are increased in the pancreatic tumor microenvironment. Finally, Stat3, a key transcription factor that determines the differentiation of TH17 lineage, is activated in the pancreatic dysplastic epithelium as well as in the stromal infiltrating cells. We have discovered that PanINs from KCiMist1 mice overexpress the IL-17RA by immunofluorescence and furthermore we confirmed this finding on human PanIN tissue arrays. Intrapancreatic injections of adenovirus encoding IL-17A, the main cytokine produced by TH17 cells, into transgenic mice after KrasG12D activation led to an increase in the progression of PanIN lesions by 6 weeks when compared with mice injected with luciferase-adenovirus. We showed a decrease in initiation and progression of PanINs in KCiMist1/CP mice that have received neutralizating antibodies against IL-17RA, IL-17A and IL-17F for 6 weeks after Kras activation. Finally, we transplanted IL-17A KO bone marrow into KCiMist1 mice and showed a significant decrease in metaplasia and PanINs formation when compared with mice transplanted with WT bone marrow. In conclusion, we have shown through three functional murine experiments that TH17 cells, recruited to the pancreas in the presence of chronic pancreatitis, can accelerate the progression of early pancreatic tumorigenesis, setting the basis for future translational studies targeting TH17 cells. This work has been supported by the training grant: NIGMS T32GMO66691. Citation Format: Florencia McAllister, Jennifer M. Bailey, Janivette Alsina, Chris Nirschl, Rachana Lankapalli, Jeffrey Roeser, Elizabeth Jaffee, Cynthia Sears, Jay K. Kolls, Charles G. Drake, Drew M. Pardoll, Steven D. Leach. TH17 cells promote early pancreatic tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2867. doi:10.1158/1538-7445.AM2013-2867

TH17 cells and early pancreatic tumorigenesis.

144 Background: Chronic pancreatitis increases the risk of developing pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human cancers. Activating Kras mutations have been detected in 30% of early pancreatic intraepithelial neoplasias (PanINs), increasing to 100% in PDAC. We hypothesized that inflammatory cells recruited to the pancreas in response to chronic injury can interact with epithelial cells harboring activated KrasG12D and affect the progression of PanIN lesions. Methods: We used the the transgenic Mist1:CreERT2; LSL-KrasG12D (KCiMist1) adult mice in which the LSL KrasG12Dallele is activated specifically in the acinar compartment. This model leads to the formation of PanINs with a classic "ductal" phenotype and the progression of lesions is accelerated by the induction of chronic pancreatitis with recurrent cerulein injections. Results: We have found that TH17 cells, a subtype of CD4+ T-helper cells known to play an active role in inflammation, are recruited to the pancreas during chronic pancreatitis and further increased upon KrasG12Dactivation. The differentiation of CD4+T cells into TH17 requires IL-6 and TGF-B, factors that are increased in the pancreatic tumor microenvironment. Stat3, a key transcription factor that determines the differentiation of TH17 lineage, is activated in the pancreatic dysplastic epithelium and in the stroma. We have discovered that PanINs from KCiMist1 mice overexpress the IL-17 Receptor (IL-17RA) by immunofluorescence and furthermore we confirmed this finding on human PanIN tissue arrays. Intrapancreatic injections of adenovirus encoding IL-17A, the main cytokine produced by TH17 cells, into KCiMist1 mice led to an increase in the progression of PanIN lesions by 6 weeks when compared with mice injected with control adenovirus. Finally, we transplanted IL-17-/- bone marrow into KCiMist1 mice and showed a significant decrease in metaplasia and PanINs formation when compared with mice transplanted with WT bone marrow. Conclusions: We found that TH17 cells, recruited to the pancreas in the presence of chronic pancreatitis, can accelerate the progression of early pancreatic tumorigenesis, setting the basis for future translational studies targeting TH17 cells.