CGAT: Cell Graph ATtention Network for Grading of Pancreatic Disease Histology Images.

Early detection of Pancreatic Ductal Adenocarcinoma (PDAC), one of the most aggressive malignancies of the pancreas, is crucial to avoid metastatic spread to other body regions. Detection of pancreatic cancer is typically carried out by assessing the distribution and arrangement of tumor and immune cells in histology images. This is further complicated due to morphological similarities with chronic pancreatitis (CP), and the co-occurrence of precursor lesions in the same tissue. Most of the current automated methods for grading pancreatic cancers rely on extensive feature engineering involving accurate identification of cell features or utilising single number spatially informed indices for grading purposes. Moreover, sophisticated methods involving black-box approaches, such as neural networks, do not offer insights into the model's ability to accurately identify the correct disease grade. In this paper, we develop a novel cell-graph based Cell-Graph Attention (CGAT) network for the precise classification of pancreatic cancer and its precursors from multiplexed immunofluorescence histology images into the six different types of pancreatic diseases. The issue of class imbalance is addressed through bootstrapping multiple CGAT-nets, while the self-attention mechanism facilitates visualization of cell-cell features that are likely responsible for the predictive capabilities of the model. It is also shown that the model significantly outperforms the decision tree classifiers built using spatially informed metric, such as the Morisita-Horn (MH) indices.

Classification of pancreaticobiliary maljunction and clinical features in children.

BACKGROUND: In 2015, the Committee on Diagnostic Criteria of the Japanese Study Group on Pancreaticobiliary Maljunction (PBM) proposed a classification of PBM into four types: (A) stenotic type, (B) non-stenotic type, (C) dilated channel type, and (D) complex type. To validate this classification and clarify the clinical features of the four types of PBM, a retrospective multicenter study was conducted. METHODS: The study group of 317 children with PBM was divided into the four types of PBM. Clinical features, preoperative complications, operations, and postoperative pancreatic complications were evaluated. RESULTS: All patients underwent excision of the extrahepatic bile duct. In type A, the age was younger and there was a higher incidence of cystic dilatation. Non-dilatation of the common bile duct was frequently seen in type B. Abdominal pain with hyperamylasemia was frequently seen in types B and C. In particular, the incidence of protein plugs and biliary perforation was high in type C (56.1% and 14.3%, respectively). The overall incidence of acute pancreatitis was 7.3%. Pancreatitis after excisional surgery was rare in the children in this study. Two patients with type D (0.6%) developed chronic pancreatitis postoperatively. CONCLUSIONS: This proposed classification is simple and correlates well with clinical features.

The distal classification and management of choledochal cyst in adults: Based on the relation between cyst and pancreatic duct.

Todani classification is extensively used to guide the surgical strategy of choledochal cysts, but no systematic investigations on the distal management of intrapancreatic choledochal cysts have been conducted. This study reports the distal classification and management of choledochal cysts in adults based on the relation between the cyst and pancreatic duct. Patients with choledochal cyst who underwent operation, including distal management, in our department from January 2009 to December 2014 were retrospectively reviewed. Patients presenting symptoms, coexisting diseases, surgical treatment, perioperative complications, and long-term follow-up according to the distal classification of choledochal cyst were analyzed. A total of 54 patients with choledochal cyst were included in the present retrospective study. Based on the distal classification of choledochal cyst, 39 patients (72.22%) were type 1, 13 patients (24.07%) were type 2, and 2 patients (3.70%) were type 3. Thirty-nine type 1 patients and 10 type 2 patients underwent excision of intrapancreatic choledochal cyst or bile duct. Three type 2 patients received excision of distal cylindrical cyst and papilla, followed by pancreatic duct plasty with duodenum mucosa. One type 3 patient underwent endoscopic sphincteroplasty, and another type 3 patient underwent transduodenal sphincteroplasty. After the operation, 11 patients (20.37%, 11/54) had short-term perioperative complications. The long-term follow-up results showed that the satisfactory rate (excellent and good outcomes) was 95.83%. Current distal classification of choledochal cysts could provide a more targeted strategy for complete excision to eliminate potential dead space within the pancreas, protect the pancreatic duct, and prevent reoperation.

"Biliary Diseases with Pancreatic Counterparts": Cross-sectional Imaging Findings.

On the basis of the similarities in the histopathologic findings and the clinical-biologic behaviors of select biliary and pancreatic conditions, a new disease concept, "biliary diseases with pancreatic counterparts," has been proposed. Both nonneoplastic and neoplastic pathologic conditions of the biliary tract have their counterparts in the pancreas. Immunoglobulin G4 (IgG4)-related sclerosing cholangitis is the biliary manifestation of IgG4-related sclerosing disease, and type 1 autoimmune pancreatitis is its pancreatic counterpart. People with chronic alcoholism can develop peribiliary cysts and fibrosis as well as pancreatic fibrosis and chronic pancreatitis simultaneously. Pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm are considered pancreatic counterparts for the biliary neoplasms of extrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the biliary tract, and hepatic mucinous cystic neoplasm, respectively. The anatomic proximity of the biliary tract and the pancreas, the nearly simultaneous development of both organs from the endoderm of the foregut, and the presence of pancreatic exocrine acini within the peribiliary glands surrounding the extrahepatic bile ducts are suggested as causative factors for these similarities. Interestingly, these diseases show "nearly" identical findings at cross-sectional imaging, an observation that further supports this new disease concept. New information obtained with regard to biliary diseases can be used for evaluation of pancreatic abnormalities, and vice versa. In addition, combined genetic and molecular studies may be performed to develop novel therapeutic targets. For both biliary and pancreatic diseases, imaging plays a pivotal role in initial diagnosis, evaluation of treatment response, efficacy testing of novel drugs, and long-term surveillance.

[Typing and surgical treatment choice for pancreatic ductal stone].

OBJECTIVE: To explore the improvement of typing and reasonable surgical treatment for pancreatic ductal stone (PDS). METHODS: Totally 89 patients with pancreatic ductul stone treated underwent surgeries from January 2000 to December 2012 were involved into this study. There were 57 male and 32 female patients, the average age was (52 ± 23) years. According to the magnetic resonance cholangiopancreatography imaging and finding during surgery, pancreatolithiasis was classified into three types: type I, the stones were located in the main pancreatic duct; type II, the stones were located both in main and branch pancreatic duct; type III, the stones were diffusely scattered in the branch pancreatic duct; the position of PDS within pancreatic parenchyma were subtitled. In this group, 43 type I PDS were extracted with endoscopic papillotomy or endoscopic pancreatic sphincterotomy, or pancreatolithotomy plus pancreato-jejunal lateral anastomosis with wide anastomotic stoma; 39 type II cases were treated by pancreatolithotomy plus pancreato-jejunal lateral anastomosis or/and resection of pancreatic section; 7 type III PDS were managed with resection of pancreatic section. RESULTS: All surgeries were performed successfully. Among complications, 6 cases (6.7%) were pancreatic leakage which recovered after systematic non-surgical treatment, 2 cases (2.2%) were anastomotic bleeding which led to 1 death, 6 cases (6.7%) were residual pancreatolithiasis in branch pancreatic duct type. Seventy-eight patients were followed up for 6 to 131 months, 57 cases were still alive so far. Five cases were intermittent abdominal pain, 7 cases were diabetes resulted from 2 subtotal pancreatectomy and 5 distal pancreatectomy, 5 cases occurred pancreatolithiasis recurrence and 3 underwent secondary surgeries. CONCLUSIONS: The basis of this modified typing of pancreatolithiasis is the position of stone in pancreatic duct rather than pancreas parenchyma. It is more important and valuable for surgical principle of taking stones out completely and maintaining pancreatic function.

Construction of classifier based on MPCA and QSA and its application on classification of pancreatic diseases.

A novel method is proposed to establish the classifier which can classify the pancreatic images into normal or abnormal. Firstly, the brightness feature is used to construct high-order tensors, then using multilinear principal component analysis (MPCA) extracts the eigentensors, and finally, the classifier is constructed based on support vector machine (SVM) and the classifier parameters are optimized with quantum simulated annealing algorithm (QSA). In order to verify the effectiveness of the proposed algorithm, the normal SVM method has been chosen as comparing algorithm. The experimental results show that the proposed method can effectively extract the eigenfeatures and improve the classification accuracy of pancreatic images.

Incretin-based therapies in the treatment of type 2 diabetes--more than meets the eye?

A lot of contradictory data regarding the serious side effects of incretin-based therapies are currently available, with more being prepared or published every month. Considering the widespread use of these drugs it should be considered a priority to establish both short- and long-term risks connected with incretin treatment. We performed an extensive literature search of the PubMed database looking for articles dealing with connections between incretin-based therapies and pancreatitis, pancreatic cancer, thyroid cancer and other neoplasms. Data obtained indicate that GLP-1 agonists and DPPIV inhibitors could increase the risk of pancreatitis and pancreatic cancer, possibly due to their capacity to increase ductal cell turnover, which has previously been found to be up-regulated in patients with obesity and T2DM. GLP-1 analogues exenatide and liraglutide seem to be connected with medullary thyroid carcinoma in rat models and, surprisingly, GLP-1 receptors have been found in papillary thyroid carcinoma, currently the most common neoplasm of the thyroid gland in humans. Changes in expression of DPPIV have been described in ovarian carcinoma, melanoma, endometrial adenocarcinoma, prostate cancer, non-small cell lung cancer and in certain haematological malignancies. In most cases loss of DPPIV activity is connected with a higher grading scale, more aggressive tumour behaviour and higher metastatic potential. In conclusion animal and human studies indicate that there could be a connection between incretin-based therapies and pancreatitis, pancreatic cancer, thyroid cancer and other neoplasms. Therefore whenever such therapy is started it would be wise to proceed with caution, especially if personal history of neoplasms is present.

Efficacy of carcinogenic embryonic antigen in differential diagnosis of diseases of pancreas and liver--a comparative study in a tertiary care hospital of Western Nepal.

OBJECTIVE: The objective of our present study was to assess the efficacy of carcinoembryonic antigen (CEA) for differentiating and diagnosis of pancreatic and liver diseases in Pokhara valley. MATERIALS AND METHODS: A hospital based retrospective study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2011 and 31st October, 2011. Estimation of CEA was performed by ELISA reader for all cases. Approval for the study was obtained from the institutional research ethical committee. RESULTS: Of the 771 subjects, 208 (27%), 60(7.8%), 240(31.1%), 54(7.0%) , 75(9.7%), 59(7.7%), 75(9.7%) cases were of active chronic hepatitis , cryptogenic cirrhosis, alcoholic cirrhosis, primary biliary cirrhosis, hepatoma, acute or chronic pancreatitis, carcinoma of pancreas respectively. The majority of cases (104) of active chronic hepatitis had CEA levels <5 ng/ml(50%). CEA levels were found to be increased in cases of alcoholic cirrhosis with maximum number of cases (106) in range of 10 to 20 ng/ml (44%). There were no cases having more than 20 ng/ml of CEA in primary biliary cirrhosis and acute or chronic pancreatitis. In cases of pancreatic cancer, maximum number of cases (35) were having CEA >20 ng/ml(47%). CONCLUSION: High levels of CEA are associated with advanced stage of disease. CEA can thus provide an important improvement in the diagnosis by differentiating pancreatic cancer especially from chronic pancreatitis when there is a high suspicion of malignancy. Increased CEA levels may also signify progression from benign to malignant transformation in the liver.

Classification of probe-based confocal laser endomicroscopy findings in pancreaticobiliary strictures.

BACKGROUND AND STUDY AIMS: The accurate diagnosis of indeterminate pancreaticobiliary strictures presents a clinical dilemma. Probe-based confocal laser endomicroscopy (pCLE) offers real-time in vivo microscopic tissue examination that may increase sensitivity for the detection of malignancy. the objective of this study was to develop and validate a standard descriptive classification of pcle in the pancreaticobiliary system. PATIENTS AND METHODS: A total of 102 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with pCLE to assess indeterminate pancreaticobiliary strictures were enrolled in a multicenter registry; 89 of these patients were evaluable. Information and data on the following were collected prospectively: clinical, ERCP, tissue sampling, pCLE, and follow-up. A uniform classification of pCLE findings ("Miami Classification") was developed, consisting of a set of image interpretation criteria. Thereafter, these criteria were tested through blinded consensus review of 112 randomized pCLE videos from 47 patients, and inter-observer variability was assessed in 42 patients . RESULTS: A consensus definition of the specific criteria of biliary and pancreatic pCLE findings for indeterminate strictures was developed. Single-image interpretation criteria did not have a high enough sensitivity for predicting malignancy. However, combining two or more criteria significantly increased the sensitivity and predictive values. The characteristics most suggestive of malignancy included the following: thick white bands (>20 µm), or thick dark bands (>40 µm), or dark clumps or epithelial structures. These provided sensitivity, specificity, positive predictive value, and negative predictive value of 97%, 33%, 80%, and 80% compared with 48%, 100%, 100%, and 41% for standard tissue sampling methods. Inter-observer variability was moderate for most criteria. CONCLUSION: The Miami Classification enables a structured, uniform, and reproducible description of pancreaticobiliary pCLE. Combining individual characteristics improves the sensitivity for the detection of malignancy.

Morphometric image analysis of pancreatic disease by ThinPrep liquid-based cytology.

Liquid-based cytology preparations are being increasingly used in nongynecologic specimens. The aim of this study is to objectively evaluate pancreatic disease by ThinPrep (TP) liquid-based cytology using morphometric image analysis. In all, 30 patients undergoing preoperative evaluation of pancreatic disease by TP were investigated from January to April 2009. We analyzed cytological features, such as cluster area, cluster circularity, and nucleus area, using morphometric image analysis software and further investigated the cytological findings of TP to determine which are useful for detecting malignancy. Pancreatic cytological findings of TP showed small clusters and loss of cluster irregularity in malignant cells. The patients were diagnostically categorized as inadequate, normal or benign, indeterminate, suspected malignancy, and malignant in 6.6% (2), 46.7% (14), 13.3% (4), 13.3% (4), and 20.0% (6) of the cases, respectively. Morphometric image analysis of 28 patients by TP,excluding two inadequate patients, showed no statistical difference in cluster area or cluster circularity among these cytological categories. In contrast, nucleus area in the normal or benign, indeterminate, suspected malignancy, and malignant categories was 17.6, 57.2, 67.4, and 68.0 µm(2) , respectively, and was associated with diagnostic category (P < 0.05). Pancreatic cytological findings of TP preparations generally show small, round cluster shapes in pancreatic disease; however, nucleus size is a more important criteria for detecting malignancy by TP in pancreatic disease.

¹8F-FDG PET/CT imaging of the pancreas: spectrum of diseases.

Since the introduction of integrated positron emission tomography-computed tomography (PET/CT), it has a great impact on the field of oncology. Comparing to other conventional scanners, only PET/CT is capable of providing important information on accurate detecting, staging/restaging, and post-therapeutic monitoring of many cancers. Many studies have demonstrated that PET/CT changes the management in approximately 30% of all cancer patients. Because 2-((18)F)-fluoro-2-deoxy-D-glucose (FDG) is a nonspecific tracer, understanding the PET/CT limitations and pitfalls for various pancreatic conditions can lead to more accurate interpretation of PET/CT images, which ultimately would impact patient care. As a result, it is important for radiologists and other clinicians to familiarize themselves with a wide spectrum of pancreatic PET/CT findings simulating cancer from benign entities.

Portal annular pancreas. A rare variant and a new classification.

CONTEXT: Portal annular pancreas is a rare congenital anomaly resulting from fusion of the pancreatic parenchyma around the portal vein/superior mesenteric vein. It is asymptomatic, but could have serious consequences during pancreatic surgery, if unrecognized. We describe a variant of this anomaly encountered during pancreaticoduodenectomy and propose a new classification. CASE REPORT: We report a 51-year-old male who underwent a pancreaticoduodenectomy for periampullary carcinoma. After division of the pancreatic neck, a sheath of tissue was found posterior and extending to the left of the portal vein. When we divided this tissue, a large duct was encountered; this duct communicated with the main pancreatic duct. On review of the CT images, the main pancreatic duct was seen to be passing posterior to the portal vein and a smaller accessory pancreatic duct was present anterior to the portal vein. We describe the surgical implications. CONCLUSION: This variant of portal annular pancreas has not yet been reported during pancreaticoduodenectomy and we propose a new classification for this fusion anomaly.

Prevalence of type III anomalous pancreaticobiliary junction in a tertiary care hospital of North India.

CONTEXT: Anomalous junction of pancreaticobiliary ducts is a condition in which the pancreatic duct and the bile duct join outside the duodenal wall with a long common channel. The most accepted classification of various types of anomalous pancreaticobiliary junction is the new Komi classification. The majority of cases of type III anomalous pancreaticobiliary junction are reported from Japan and very seldom from outside Japan. This study evaluates the prevalence of type III anomalous pancreaticobiliary junction in the Indian population. OBJECTIVE: To retrospectively evaluate the prevalence of type III anomalous pancreaticobiliary junction revealed by endoscopic retrograde cholangiopancreatography (ERCP) examinations carried out between 1985 and 2005. DESIGN: ERCP records of 3,827 patients satisfying inclusion criteria between 1985 and 2005 were retrospectively analyzed. MAIN OUTCOME MEASURE: Patients demonstrating anomalous pancreaticobiliary junction were identified and classified according to the new Komi classification. RESULTS: A total of 101 patients had anomalous pancreaticobiliary junction (2.6% of all ERCP). Only 2 patients (2.0% of all anomalous pancreaticobiliary junction cases and 0.05% of all ERCP examinations) had type III anomalous pancreaticobiliary junction. Both cases were associated with choledochal cysts and chronic pancreatitis. CONCLUSION: Type III anomalous pancreaticobiliary junction is a rare occurrence in Indian patients as compared to Japanese patients in whom the majority of cases are reported. This demographic variation is still unexplained.

Correlation of liver-spleen scan findings with modified Child-Pugh classification / Correlation of liver-spleen scan findings with modified Child-Pugh classification

Background. The Child-Pugh classification is used as an index of liver function. We assessed the relationship between modified Child score and sulfur colloid liver-spleen scintigraphy in histologically confirmed cirrhosis. Method. Following injection of 185 MBq 99mTechnetium-sulfur colloid, anterior and posterior images were obtained at 30 minutes with 500,000 counts. Liver-spleen scintigraphy pattern was divided visually into three categories: A (liver uptake $ spleen uptake, without visualization of ribs and vertebrae), B (spleen uptake > liver uptake without visualization of ribs and vertebrae), and C (remarkable visualization of ribs and vertebrae). Results. Of 36 patients, 14 (38.8 %), 19 (58.8 %) and 3 (8.3 %) patients were categorized into Child-Pugh grades A, B and C, respectively, whereas 13 (36.1 %), 12 (33.3 %) and 11 (30.6 %) patients were categorized into scintigraphic grades A, B and C, respectively. In 14 patients the results of Child and scan classifications were in agreement, but in 22 patients the results were discordant. Kappa value was 0.072 (poor agreement). Conclusion. There is no correlation between scintigraphic and Child-Pugh classifications. Scintigraphic classification may present a marker of body reactions to the disease, independent of Child-Pugh modified classification. Further studies are needed to determine which one of these classifications has better concordance with the patient's outcome

Fundamentos. Se usa la clasificación de Child-Pugh como índice de la función hepática. Hemos evaluado la relación de la puntuación de Child modificada y la gammagrafía del hígado-bazo con sulfuro coloidal en cirrosis confirmada histológicamente. Método. Después de la inyección de 185 MBq de 99mTc-sulfuro coloidal, se adquirieron imágenes en proyecciones anterior y posterior a los 30 minutos de la inyección con 500.000 cuentas. El patrón de la gammagrafía del hígado-bazo fue dividido visualmente en tres categorías: A (captación del hígado $ captación del bazo, sin visualización de las costillas y vértebras), B (captación del bazo > captación del hígado sin visualización de las costillas y vértebras) y C (visualización destacada de las costillas y las vértebras). Resultados. De los 36 pacientes, 14 (38,8 %), 19 (58,8 %) y 3 (8,3 %) pacientes fueron agrupados en grados A, B y C de Child-Pugh, respectivamente, mientras 13 (36,1 %), 12 (33,3 %) y 11 (30,6 %) pacientes fueron agrupados en grados A, B y C de gammagrafía, respectivamente. En 14 pacientes los resultados de Child y las clasificaciones de la gammagrafía concordaban, pero en 22 pacientes los resultados fueron discordantes. El valor kappa fue 0,072 (concordancia pobre). Conclusión. No hay correlación entre gammagrafía y las clasificaciones de Child-Pugh. La clasificación de la gammagrafía puede ser un marcador de las reacciones corporales a la enfermedad, independiente de la clasificación modificada de Child-Pugh. Hacen falta más estudios para determinar cuáles de estas clasificaciones tienen mejor concordancia con el pronóstico del paciente

[The classification and management of pancreatic duct stone].

OBJECTIVE: To set up a stand for surgical classification of pancreatic duct stone and evaluate the benefits of different management according to the classification. METHODS: Retrospectively analysis the diagnosis and prognosis of different management of 33 cases pancreatic duct stones to establish a new standard of classification and strategy of management of pancreatic duct stone. RESULTS: According to the results of imaging examination (B-US, CT, ERCP) and finding during surgery, pancreatic duct stone can be classified into four different types: Type I: The stones mainly located in the head of pancreas. Endoscopic pancreas drainage and remove of stones is the first line choice of treatment. If it fail the Whipple procedure should be applied. Type II, The stones mainly located in the body of pancreas. It can be treated by Pusetow procedure. Type III, The stones mainly located in the tail of pancreas. The resection of the tail of pancreas or combined with spleenectomy was recommended for the management of this type stones. Type IV, The stones can be found from the head to tail of the main duct of pancreas. The Pusetow-Gillesby procedure or dividing of the neck of pancreas removing stones from both ends of pancreatic duct and reconstructed by two ends pancreatic duct-ileostomy in Roux-en-Y fashion are the choice of management. CONCLUSION: The invadulaized strategy of the management based upon correct diagnosis and classification play the most important role in the treatment of pancreatic duct stone.

Imaging diagnosis of pancreato-biliary diseases: a control study.

AIM: To evaluate the clinical value of various imageological methods in diagnosing the pancreato-biliary diseases and to seek the optimal procedure. METHODS: Eighty-two cases of pancreato-biliary diseases confirmed by surgery and pathology were analyzed. There were 38 cases of cholelithiasis, 34 cases of pancreato-biliary tumors and 10 other cases. The imageological methods included B-US, CT, ERCP, PTC, cross-sectional MRI and MR cholangiopancreatography (MRCP). RESULTS: The accuracy rate of MRCP in detecting the location of pancreato-biliary obstruction was 100%. In differentiating malignant from benign obstruction, the sensitivity of the combination of MRCP and cross-sectional MRI was 82.3%, the specificity was 93.8%, and the accuracy rate was 89.0%. The accuracy rate for determining the nature of obstruction was 87.8%, which was superior to that of B-US (P=0.0000) and CT (P=0.0330), but there was no significant difference between direct cholangiopancreatography and the combination of MRCP and conventional MRI (P=0.6666). CONCLUSION: In most cases, MRCP can substitute direct cholangiopancreatography for diagnosis. The combination of MRCP and cross-sectional MRI should be considered as an important means in diagnosing the pancreato-biliary diseases, pre-operative assessment and post-operative follow-ups.