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1. Structural, functional and molecular dynamics analysis of cathepsin B gene SNPs associated with tropical calcific pancreatitis, a rare disease of tropics

Author

Garima Singh, Sri Krishna jayadev Magani, Rinku Sharma, Basharat Bhat, Ashish Shrivastava, Madhusudhan Chinthakindi, and Ashutosh Singh

Subjects
Tropical Calcific Pancreatitis, Pancreatitis, Cathepsin B, Molecular dynamic simulation, Single nucleotide variants, Medicine, Biology (General), QH301-705.5
Abstract

Tropical Calcific Pancreatitis (TCP) is a neglected juvenile form of chronic non-alcoholic pancreatitis. Cathepsin B (CTSB), a lysosomal protease involved in the cellular degradation process, has recently been studied as a potential candidate gene in the pathogenesis of TCP. According to the Cathepsin B hypothesis, mutated CTSB can lead to premature intracellular activation of trypsinogen, a key regulatory mechanism in pancreatitis. So far, CTSB mutations have been studied in pancreatitis and neurodegenerative disorders, but little is known about the structural and functional effect of variants in CTSB. In this study, we investigated the effect of single nucleotide variants (SNVs) specifically associated with TCP, using molecular dynamics and simulation algorithms. There were two non-synonymous variants (L26V and S53G) of CTSB, located in the propeptide region. We tried to predict the effect of these variants on structure and function using multiple algorithms: SIFT, Polyphen2, PANTHER, SDM sever, i-Mutant2.0 suite, mCSM algorithm, and Vadar. Further, using databases like miRdbSNP, PolymiRTS, and miRNASNP, two SNPs in the 3′UTR region were predicted to affect the miRNA binding sites. Structural mutated models of nsSNP mutants (L26V and S53G) were prepared by MODELLER v9.15 and evaluated using TM-Align, Verify 3D, ProSA and Ramachandran plot. The 3D mutated structures were simulated using GROMACS 5.0 to predict the impact of these SNPs on protein stability. The results from in silico analysis and molecular dynamics simulations suggested that these variants in the propeptide region of Cathepsin B could lead to structural and functional changes in the protein and thus could be pathogenic. Hence, the structural and functional analysis results have given interim conclusions that these variants can have a deleterious effect in TCP pathogenesis, either uniquely or in combination with other mutations. Thus, it could be extrapolated that Cathepsin B gene can be screened in samples from all TCP patients in future, to decipher the distribution of variants in patients.

Published
2019
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2. National Liver Allocation Policy—Consensus Document by the Liver Transplantation Society of India for a Nationally Uniform System of Allocation of Deceased Donor Liver Grafts

Author

Mettu S. Reddy, Surendra K. Mathur, Surendran Sudhindran, Subhash Gupta, Mohamed Rela, Arvinder S. Soin, Darius Mirza, Sonal Asthana, Madhusudhan Chinthakindi, Mathew Jacob, Vinay Kumaran, Pranjal Modi, Ravi Mohanka, Gomathy Narasimhan, Sujoy Pal, Viniyendra Pamecha, Amit Rastogi, Sanjiv Saigal, and Manav Wadhawan

Subjects
Hepatology
Published
2023
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3. Contrast-enhanced ultrasound for the evaluation of hepatic artery occlusion after liver transplantation

Author

Madhusudhan Chinthakindi, ChennaKesava Rao Ragam, Ravi Mohan Thogary, Vinod Kumar Jyothiprakashany, Vikas K Yadav, and Nori Madhavi

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Gold standard (test), Liver transplantation, medicine.disease, Revascularization, Thrombosis, medicine.anatomical_structure, Angiography, medicine, Radiology, Artery occlusion, business, Contrast-enhanced ultrasound, Artery
Abstract

Introduction:Vascular complications after liver transplantation remain a major threat to the survival of recipients.HAT is a major cause of graft loss and patient mortality, with an incidence between 3% to 8% in transplant recipients.Early detection of HAT is critical because urgent revascularization is required to avoid severe graft loss. Although ultrasound is the preferred first-line imaging modality in patients with suspected HAT, the accuracy and positive predictive value of HAT on Doppler US are reported to be low. Moreover, Doppler examination of the hepatic vasculature is time consuming and requires a high level of operator skill. Conventional angiography remains the gold standard for diagnosis. Recently, contrast-enhanced ultrasound (CEUS) has begun providing real-time angiographic-like images of vessels at bed side and allowing the accurate diagnosis of arterial diseases such as hepatic artery thrombosis. The purpose of this study was to evaluate the efficacy of CEUS in detecting HAT after liver transplantation: Materials and Methods: This is a retrospective data of the medical records of patients undergoing Liver transplantation in the Osmania General Hospital, Hyderabad between 2016 to 2018. Status of hepatic vascular assessment following liver transplantation done by conventional Doppler Ultra sonography and Contrast Enhanced Ultrasonography tests were obtained from registries of medical records. Results:23 cases of post Liver transplantation aged between 4years and 58 years, with a median age of 30 years were included in the analysis. There were 20 males and 3 females. 14 patients underwent DDLT, 7 patients underwent LDLT, 1underwent split Liver transplantation and another 1 patient underwent Auto liver transplantation. Doppler US was inconclusive regarding patency of the hepatic artery (HA) circulation in 5 (21.7 %) of 23 transplantations. CEUS was performed in these 5 patients and detected HA thrombosis (HAT) in 2 cases and patent HA in 3 transplants. These 5 Transplants were confirmed by CT Angiography /conventional Angiography. In the subset of transplantations examined with CEUS, the sensitivity, specificity and accuracy of CEUS were 100%. CEUS was done at bedside without any Radiation and Nephro toxicity. In approximately 21.7% of cases, conventional Doppler US did not provide sufficient visualization of the HA after liver transplantation. In these cases, correct diagnosis was achieved by supplementary CEUS. Conclusion:CEUS may be a new approach for early diagnosis of postoperative vascular complications after Liver Transplantation, and it can be performed at the bedside. It is safe will not cause any nephron toxicity and Radiation. CEUS is a fast, non-ionizing imaging modality for the initial exclusion of vascular complications after liver transplantation. CEUS shows a high specificity and PPV in the detection of vascular complications. In unclear cases CT still is considered as the gold standard

Published
2018
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4. A study of Diagnosis and surgical management of pancreatic insulinoma

Author

Madhusudhan Chinthakindi, Ramalingam Pratap Reddy, Ravimohan Thogari, and Kyyoda Prashanth

Subjects
Pancreatic Insulinoma, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Splenectomy, Neuroendocrine tumors, medicine.disease, Palpation, medicine.anatomical_structure, Pancreatic tumor, Pancreatectomy, medicine, Radiology, Pancreas, business, Insulinoma
Abstract

Introduction: Insulinomas are the most common functioning neuroendocrine tumors of the pancreas, occurring in almost 1-4 per 1 million persons each year. They pose a challenge for pre-operative localization. Many invasive and non-invasive methods exist for localization of an insulinoma. Intra-operative ultrasonography (IOUS) with palpation can be done for tumors not localized by conventional imaging modalities. Pancreas Preserving surgery is the treatment of choice. This article gives an overview on localization and surgical strategies for treatment of insulinoma. Materials and Methods: This is a retrospective data of the patients undergoing surgical treatment of insulinoma in the Osmania General Hospital, Hyderabad between 2007 to 2017. Demographic data, symptoms and diagnostic tests and type of resections were analyzed from medical records. All patients had a complete intraoperative exploration of the pancreas done by digital palpation and intra operative ultrasonography. Results: 10 cases (6 males and 4 females) of insulinoma aged between 22 and 55 years, with a median age of 30 years were included in the analysis. The size of the insulinoma ranged between 1.2 to 3 cm with average size of 2.14cm. 8 patients presented with Neuro glycopenicsymptoms however sympatho adrenergic symptoms were present in all cases. Different modalities were employed for pre-operative localization of these patients out of which 5 cases were localized with CT, 2 cases with MRI, 1 case with EUS, 2 of them could not be localized preoperatively were localized by IOUS. Tumor was in Head 2 cases, in the neck1 case and in the body/ Tail in 7 cases. 2 patients underwent Enucleation, 5 underwent distal pancreatectomy and splenectomy, 2 under went distal pancreatectomy and 1 underwent central pancreatectomy. 4 had pancreatic leak. All are symptom free and no episode of hypoglycemia at the time of discharge. Conclusion: Insulinomas are the most common neuroendocrine tumors of the pancreas. Surgical resection is the treatment of choice for insulinomas. From a surgical stand point, localization of the tumor is of critical importance. Intraoperative Ultrasonography with palpation gives good help in localizing the lesion.

Published
2018
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9. Diagnosis and treatment in chronic pancreatitis: an international survey and case vignette study

Author

Yama Issa, Hjalmar C. van Santvoort, Paul Fockens, Marc G. Besselink, Thomas L. Bollen, Marco J. Bruno, Marja A. Boermeester, Frank G. Moody, Claude Bertrand, Colin Johnson, Aude van Lander, Ross Carter, John B. Conneely, Frederik Berrevoet, Donzília Sousa Silva, Zong-Fang Li, Philippe Lévy, Kofi Oppong, Timothy B. Gardner, C. Mel Wilcox, Jeremy French, Michael Steer, Edward L. Bradley, Peter Layer, Bertrand Napoleon, Jorge Antonio Mosquera, D.J. Gouma, Roland Andersson, Antonio Manzelli, J.M. Klaase, Massimo Falconi, Enrique de-Madaria, Riccardo Casadei, Giuseppe Malleo, Raffaele Pezzilli, Ewa Malecka-Panas, Matthias Lohr, Julia Mayerle, Erik A.J. Rauws, Martin L. Freeman, Affirul Chairil Ariffin, Bhavin Vasavada, Paul Bo-San Lai, Jose Luis Beristain-Hernandez, Álvarez Juan, Haralds Plaudis, Dionisios Vrochides, Vincenzo Neri, Vimalraj Velayutham, Aleksey Andrianov, Joan Figueras, Kjetil Soreide, Aliaksei Shcherba, Mahir Gachabayov, Roger G. Keith, Georgios Tsoulfas, Michael Anthony Fink, Stefano Crippa, Mehrdad Nikfarjam, Dibyajyoti Bora, Rajendra Desai, Marcello Donati, Jan Jin Bong, Emma Martínez Moneo, Gareth Morris-Stiff, Ahmet Coker, Alexandre Prado de Resende, Suryabhan Sakhahari Bhalerao, Sadiq S. Sikora, Dezső Kelemen, László Czakó, Hariharan Ramesh, Oleg Rummo, Aliaksei Fedaruk, Alexey Hlinnik, Madhusudhan Chinthakindi, Traian Dumitrascu, Vyacheslav Egorov, Vincent Bettschart, Michele Molinari, E. Aldana D. Guillermo, Susan L. Orloff, Daniel Vasilev Kostov, Laurent Sulpice, Brett Knowles, Yasutoshi Kimura, Gabriele Marangoni, Rajeev Joshi, Tibor Gyökeres, null Bedin, V. Vladimir, Arpad Ivanecz, Adelmo Antonucci, Jones A.O. Omoshoro-Jones, Richard Nakache, Marco Del Chiaro, Marianne Johnstone, Tomoaki Saito, Gianpaolo Balzano, Serge Chooklin, Piero Boraschi, Walter Park, Pedro Nuno Valente Reis Pereira, Nico Pagano, Pavlos Lykoudis, Lars Ivo Partecke, Aliaksandr Siatkouski, Rosa Jorba Martín, Yasunari Kawabata, Luís Carvalho Lourenço, Carlos Marra-Lopez, Jun Kyu Lee, Nils Habbe, Robert C. Verdonk, Yliya Rabotyagova, Rupjyoti Talukdar, Luca Frulloni, Shamil Galeev, Zoltán Berger, Takeo Yasuda, Thilo Hackert, Ziyovuddin Saatov, Dimitri Aristotle Raptis, Jaume Boadas, Francesco Vitali, Livia Archibugi, Miroslav Ryska, Balazs Tihanyi, Vikesh K. Singh, Atsushi Masamune, Paul Yeaton, Kerrington D. Smith, Shrey Modi, Laura Cosen-Binker, Savio George Barreto, Eugenio Morandi, Sergio Valeri, Cintia Yoko Morioka, Luis F. Lara, Yoshifumi Takeyama, Frank G. Gress, Young-Dong Yu, Ezio Gaia, Sorin Traian Barbu, Ali Tüzün İnce, Akkraporn Deeprasertvit, Yu-Ting Chang, Stephen Olusola Abiola, Sabite Kacar, Peter Muscarella, Henri Braat, Samuel Han, Ali A. Aghdassi, Jean-Louis Frossard, Jill P. Smith, M.P. Schwartz, H.M. van Dullemen, N.G. Venneman, B.W.M. Spanier, Sjoerd Kuiken, Erwin van Geenen, Greg Beilman, Georgios Papachristou, Oscar Chapa Azuela, P. van der Schaar, Nevin Oruc, Marie-Paule Anten, William H. Nealon, Jesús García-Cano, Manol Jovani, Ziad Melki, Mustafa Mohammed Ahmed Ibrahim, M.U. Awajdarip, Mohammad Azam, K.G. Sabu, Igor Ermolaev, Shiran Shetty, Belei Oana, Juris Pokrotnieks, Malgorzata Lazuchiewicz-Kot, Riadh Bouali, Marek Winiarski, Marcus Schmitt, Mihai Rimbas, Alexander Meining, Bories Erwan, Peter N. Meier, Rainer Schoefl, Ahmed Youssef Altonbary, Igor Marsteller, Ingo Wallstabe, Skerdi Prifti, Arnaud Lemmers, M. Horvath, Ajay Kumar, Joseph J. Palermo, Issa, Y., van Santvoort, H. C., Fockens, P., Besselink, M. G., Bollen, T. L., Bruno, M. J., Boermeester, M. A., Moody, F. G., Bertrand, C., Johnson, C., van Lander, A., Carter, R., Conneely, J. B., Berrevoet, F., Sousa Silva, D., Li, Z. -F., Levy, P., Oppong, K., Gardner, T. B., Wilcox, C. M., French, J., Steer, M., Bradley, E. L., Layer, P., Napoleon, B., Mosquera, J. A., Gouma, D. J., Andersson, R., Manzelli, A., Klaase, J. M., Falconi, M., de-Madaria, E., Casadei, R., Malleo, G., Pezzilli, R., Malecka-Panas, E., Lohr, M., Mayerle, J., Rauws, E. A. J., Freeman, M. L., Ariffin, A. C., Vasavada, B., Lai, P. B. -S., Beristain-Hernandez, J. L., Juan, A., Plaudis, H., Vrochides, D., Neri, V., Velayutham, V., Andrianov, A., Figueras, J., Soreide, K., Shcherba, A., Gachabayov, M., Keith, R. G., Tsoulfas, G., Fink, M. A., Crippa, S., Nikfarjam, M., Bora, D., Desai, R., Donati, M., Bong, J. J., Martinez Moneo, E., Morris-Stiff, G., Coker, A., de Resende, A. P., Bhalerao, S. S., Sikora, S. S., Kelemen, D., Czako, L., Ramesh, H., Rummo, O., Fedaruk, A., Hlinnik, A., Chinthakindi, M., Dumitrascu, T., Egorov, V., Bettschart, V., Molinari, M., Guillermo, E. A. D., Orloff, S. L., Kostov, D. V., Sulpice, L., Knowles, B., Kimura, Y., Marangoni, G., Joshi, R., Gyokeres, T., Bedin, Vladimir, V., Ivanecz, A., Antonucci, A., Omoshoro-Jones, J. A. O., Nakache, R., Del Chiaro, M., Johnstone, M., Saito, T., Balzano, G., Chooklin, S., Boraschi, P., Park, W., Pereira, P. N. V. R., Pagano, N., Lykoudis, P., Partecke, L. I., Siatkouski, A., Martin, R. J., Kawabata, Y., Lourenco, L. C., Marra-Lopez, C., Lee, J. K., Habbe, N., Verdonk, R. C., Rabotyagova, Y., Talukdar, R., Frulloni, L., Galeev, S., Berger, Z., Yasuda, T., Hackert, T., Saatov, Z., Raptis, D. A., Boadas, J., Vitali, F., Archibugi, L., Ryska, M., Tihanyi, B., Singh, V. K., Masamune, A., Yeaton, P., Smith, K. D., Modi, S., Cosen-Binker, L., Barreto, S. G., Morandi, E., Valeri, S., Morioka, C. Y., Lara, L. F., Takeyama, Y., Gress, F. G., Yu, Y. -D., Gaia, E., Barbu, S. T., Ince, A. T., Deeprasertvit, A., Chang, Y. -T., Abiola, S. O., Kacar, S., Muscarella, P., Braat, H., Han, S., Aghdassi, A. A., Frossard, J. -L., Smith, J. P., Schwartz, M. P., van Dullemen, H. M., Venneman, N. G., Spanier, B. W. M., Kuiken, S., van Geenen, E., Beilman, G., Papachristou, G., Chapa Azuela, O., van der Schaar, P., Oruc, N., Anten, M. -P., Nealon, W. H., Garcia-Cano, J., Jovani, M., Melki, Z., Ibrahim, M. M. A., Awajdarip, M. U., Azam, M., Sabu, K. G., Ermolaev, I., Shetty, S., Oana, B., Pokrotnieks, J., Lazuchiewicz-Kot, M., Bouali, R., Winiarski, M., Schmitt, M., Rimbas, M., Meining, A., Erwan, B., Meier, P. N., Schoefl, R., Altonbary, A. Y., Marsteller, I., Wallstabe, I., Prifti, S., Lemmers, A., Horvath, M., Kumar, A., Palermo, J. J., Surgery, Amsterdam institute for Infection and Immunity, Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, CCA - Cancer Treatment and Quality of Life, CCA - Imaging and biomarkers, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, Cancer Center Amsterdam, APH - Methodology, AII - Infectious diseases, Issa, Yama, van Santvoort, Hjalmar C., Fockens, Paul, Besselink, Marc G., Bollen, Thomas L., Bruno, Marco J., Boermeester, Marja A., Moody, Frank G., Bertrand, Claude, Johnson, Colin, van Lander, Aude, Carter, Ro, Conneely, John B., Berrevoet, Frederik, Sousa Silva, Donzã­lia, Zong-Fang, Li, Lã©vy, Philippe, Oppong, Kofi, Gardner, Timothy B., Wilcox, C. Mel, French, Jeremy, Steer, Michael, Bradley, Edward L., Layer, Peter, Napoleon, Bertrand, Mosquera, Jorge Antonio, Andersson, Roland, Manzelli, Antonio, Falconi, Massimo, de-Madaria, Enrique, Casadei, Riccardo, Malleo, Giuseppe, Pezzilli, Raffaele, Malecka-Panas, Ewa, Lohr, Matthia, Mayerle, Julia, Rauws, Erik A. J., Freeman, Martin L., Ariffin, Affirul Chairil, Vasavada, Bhavin, Lai, Paul Bo-San, Beristain-Hernandez, Jose Lui, Juan, à lvarez, Plaudis, Harald, Vrochides, Dionisio, Neri, Vincenzo, Velayutham, Vimalraj, Andrianov, Aleksey, Figueras, Joan, Soreide, Kjetil, Shcherba, Aliaksei, Gachabayov, Mahir, Keith, Roger G., Tsoulfas, Georgio, Fink, Michael Anthony, Crippa, Stefano, Nikfarjam, Mehrdad, Bora, Dibyajyoti, Desai, Rajendra, Donati, Marcello, Bong, Jan Jin, Martínez Moneo, Emma, Morris-Stiff, Gareth, Coker, Ahmet, de Resende, Alexandre Prado, Bhalerao, Suryabhan Sakhahari, Sikora, Sadiq S., Kelemen, Dezså, Czakã³, Lã¡szlã³, Ramesh, Hariharan, Rummo, Oleg, Fedaruk, Aliaksei, Hlinnik, Alexey, Chinthakindi, Madhusudhan, Dumitrascu, Traian, Egorov, Vyacheslav, Bettschart, Vincent, Molinari, Michele, Guillermo, E. Aldana D., Orloff, Susan L., Kostov, Daniel Vasilev, Sulpice, Laurent, Knowles, Brett, Kimura, Yasutoshi, Marangoni, Gabriele, Joshi, Rajeev, Gyã¶keres, Tibor, Bedin, Null, Ivanecz, Arpad, Antonucci, Adelmo, Omoshoro-Jones, Jones A. O., Nakache, Richard, Del Chiaro, Marco, Johnstone, Marianne, Saito, Tomoaki, Balzano, Gianpaolo, Chooklin, Serge, Boraschi, Piero, Park, Walter, Pereira, Pedro Nuno Valente Rei, Pagano, Nico, Lykoudis, Pavlo, Partecke, Lars Ivo, Siatkouski, Aliaksandr, Martã­n, Rosa Jorba, Kawabata, Yasunari, Lourenã§o, Luís Carvalho, Marra-Lopez, Carlo, Lee, Jun Kyu, Habbe, Nil, Verdonk, Robert C., Rabotyagova, Yliya, Talukdar, Rupjyoti, Frulloni, Luca, Galeev, Shamil, Berger, Zoltã¡n, Yasuda, Takeo, Hackert, Thilo, Saatov, Ziyovuddin, Raptis, Dimitri Aristotle, Boadas, Jaume, Vitali, Francesco, Archibugi, Livia, Ryska, Miroslav, Tihanyi, Balaz, Singh, Vikesh K., Masamune, Atsushi, Yeaton, Paul, Smith, Kerrington D., Modi, Shrey, Cosen-Binker, Laura, Barreto, Savio George, Morandi, Eugenio, Valeri, Sergio, Morioka, Cintia Yoko, Lara, Luis F., Takeyama, Yoshifumi, Gress, Frank G., Young-Dong, Yu, Gaia, Ezio, Barbu, Sorin Traian, Ä°nce, Ali Tüzün, Deeprasertvit, Akkraporn, Chang, Yu-Ting, Abiola, Stephen Olusola, Kacar, Sabite, Muscarella, Peter, Braat, Henri, Han, Samuel, Aghdassi, Ali A., Frossard, Jean-Loui, Smith, Jill P., Kuiken, Sjoerd, van Geenen, Erwin, Beilman, Greg, Papachristou, Georgio, Chapa Azuela, Oscar, Oruc, Nevin, Anten, Marie-Paule, Nealon, William H., García-Cano, Jesãº, Jovani, Manol, Melki, Ziad, Ibrahim, Mustafa Mohammed Ahmed, Azam, Mohammad, Ermolaev, Igor, Shetty, Shiran, Oana, Belei, Pokrotnieks, Juri, Lazuchiewicz-Kot, Malgorzata, Bouali, Riadh, Winiarski, Marek, Schmitt, Marcu, Rimbas, Mihai, Meining, Alexander, Erwan, Borie, Meier, Peter N., Schoefl, Rainer, Altonbary, Ahmed Youssef, Marsteller, Igor, Wallstabe, Ingo, Prifti, Skerdi, Lemmers, Arnaud, Kumar, Ajay, Palermo, Joseph J., and Gastroenterology & Hepatology

Subjects
Endoscopic ultrasound, medicine.medical_treatment, Islets of Langerhans Transplantation, Practice Patterns, Diagnosis, treatment, chronic pancreatitis, survey, Bioinformatics, 0302 clinical medicine, Risk Factors, Lithotripsy, Diagnosis, 03.02. Klinikai orvostan, Endoscopy, Digestive System, Chronic, Practice Patterns, Physicians', Tomography, Digestive System Surgical Procedures, treatment, medicine.diagnostic_test, Gastroenterology, Magnetic Resonance Imaging, X-Ray Computed, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Predictive value of tests, Pancreatectomy, 030211 gastroenterology & hepatology, Autologous, medicine.medical_specialty, Clinical Decision-Making, Transplantation, Autologous, Decision Support Techniques, chronic pancreatitis, 03 medical and health sciences, Predictive Value of Tests, Pancreatitis, Chronic, medicine, Humans, survey, Pancreatic duct, Transplantation, Physicians', Hepatology, business.industry, General surgery, Gastroenterologists, Endoscopy, Magnetic resonance imaging, medicine.disease, Pancreatitis, Health Care Surveys, Tomography, X-Ray Computed, business, Digestive System
Abstract

Background The aim of the study was to evaluate the current opinion and clinical decision-making process of international pancreatologists, and to systematically identify key study questions regarding the diagnosis and treatment of chronic pancreatitis (CP) for future research. Methods An online survey, including questions regarding the diagnosis and treatment of CP and several controversial clinical case vignettes, was send by e-mail to members of various international pancreatic associations: IHPBA, APA, EPC, ESGE and DPSG. Results A total of 288 pancreatologists, 56% surgeons and 44% gastroenterologists, from at least 47 countries, participated in the survey. About half (48%) of the specialists used a classification tool for the diagnosis of CP, including the Mayo Clinic (28%), Mannheim (25%), or Buchler (25%) tools. Overall, CT was the preferred imaging modality for evaluation of an enlarged pancreatic head (59%), pseudocyst (55%), calcifications (75%), and peripancreatic fat infiltration (68%). MRI was preferred for assessment of main pancreatic duct (MPD) abnormalities (60%). Total pancreatectomy with auto-islet transplantation was the preferred treatment in patients with parenchymal calcifications without MPD abnormalities and in patients with refractory pain despite maximal medical, endoscopic, and surgical treatment. In patients with an enlarged pancreatic head, 58% preferred initial surgery (PPPD) versus 42% initial endoscopy. In patients with a dilated MPD and intraductal stones 56% preferred initial endoscopic ± ESWL treatment and 29% preferred initial surgical treatment. Conclusion Worldwide, clinical decision-making in CP is largely based on local expertise, beliefs and disbeliefs. Further development of evidence-based guidelines based on well designed (randomized) studies is strongly encouraged.

Published
2017
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10. Structural, functional and molecular dynamics analysis of cathepsin B gene SNPs associated with tropical calcific pancreatitis, a rare disease of tropics

Author

Ashutosh Singh, Rinku Sharma, Jayadev Msk, Basharat Bhat, Madhusudhan Chinthakindi, and Garima Singh

Subjects
education.field_of_study, In silico, Population, Coding region, Single-nucleotide polymorphism, MiRNA binding, MODELLER, Computational biology, Biology, education, Gene, Cathepsin B
Abstract

Tropical Calcific Pancreatitis (TCP) is a neglected juvenile form of chronic non-alcoholic pancreatitis. Cathepsin B (CTSB), a lysososmal protease involved in cellular degradation process, is recently been studied as a potential candidate gene in the pathogenesis of TCP. According to cathepsin B hypothesis, mutated CTSB can lead to premature intracellular activation of trypsinogen, which is a key regulatory mechanism in pancreatitis. So far, CTSB mutations have been studied in pancreatitis and neurodegenerative disorders but little is known about the structural and functional effect of variants in CTSB. In this study, we investigated the effect of single nucleotide variants (SNVs) associated with TCP, using molecular dynamics and simulation algorithms. There were two non-synonymous variants in the coding region (L26V and S53G) of CTSB, located in the propeptide region. We tried to predict the effect of these variants on structure and function using multiple algorithms: SIFT, Polyphen2, Panther, SDM sever, i-Mutant2.0 suite, mCSM algorithm and Vadar. Further, using databases like miRdbSNP, PolymiRTS and miRNASNP, two SNPs in 3’UTR region were predicted to affect the miRNA binding sites. Structural mutated models of nsSNP mutants (L26V and S53G) were prepared by MODELLER v9.15 and evaluated using TM-Align, Verify 3D, ProSA and Ramachandran plot. The results showed that the models (L26V and S53G) were of high accuracy. The 3D mutated structures were simulated using GROMACS 5.0 to predict the impact of these SNPs on protein stability. The results from in silico analysis and molecular dynamics simulations suggested that these variants in the propeptide region of cathepsin B could lead to structural and functional changes in the protein. Hence, the structural and functional analysis results have given interim conclusions that these variants can have deleterious effect in TCP and thus should be screen in samples from all TCP patients to decipher its distribution in patient population.

Published
2018
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