Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.
© 2006 S. Karger AG, Basel and IAP
- Intraductal papillary mucinous neoplasm
- Mucinous cystic neoplasm
- Guidelines for management of IPMN/MCN
- Pancreatic neoplasm
- Kimura W, Nagai H, Kuroda A, et al: Analysis of small cystic lesions of the pancreas. Int J Pancreatol 1995;18:197–206.
- Fernandez-del Castillo C, Targarona J, Thayer SP, et al: Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg 2003;138:427–433.
- Kloppel G, Solcia, E, Longnecker DS, Capella C, Sobin LH: World Health Organization International Histological Typing of Tumors of the Exocrine Pancreas. Berlin, Springer, 1996, pp 1–61.
- Longnecker DS, Adler G, Hruban RH, Kloppel G: Intraductal papillary-mucinous neoplasms of the pancreas; in Hamilton SR, Aaltonen LA (eds): World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of the Digestive System. Lyon, IARC Press, 2000, pp 237–241.
- Furukawa T, Takahashi T, Kobari M, Matsuno S: The mucus-hypersecreting tumor of the pancreas. Development and extension visualized by three-dimensional computerized mapping. Cancer 1992;70:1505–1513.
- Yamaguchi K, Chijiwa K, Shimizu S, Yokohata K, Morisaki T, Tanaka M: Comparison of endoscopic retrograde and magnetic resonance cholangiopancreatography in the surgical diagnosis of pancreatic diseases. Am J Surg 1998;175:203–208.
- Koito K, Namieno T, Ichimura T, Yama N, Hareyama M, Morita K, Nishi M: Mucin-producing pancreatic tumors: comparison of MR cholangiopancreatography with endoscopic retrograde cholangiopancreatography. Radiology 1998;208:231–237.
- Procacci C, Carbognin G, Accordini S, Biasiutti C, Guarise A, Lombardo F, Ghirardi C, Graziani R, Pagnotta N, De Marco R: CT features of malignant mucinous cystic tumors of the pancreas. Eur Radiol 2001;11:1626–1630.
- Kobayashi G, Fujita N, Lee S, et al: Correlation between ultrasonographic findings and pathological diagnosis of the mucin producing tumor of the pancreas (in Japanese with English abstract). Nippon Schokakibyo Gakkai Zasshi (Jpn J Gastroenterol) 1990;87:235–242.
- Kobayashi G, Fujita N, Noda Y, et al: Three morphological types of mucinous cystic tumor of the pancreas: correlation between morphological features and histological findings; in Wakui A, Yamauchi H, Ouchi K (eds): Carcinoma of the Pancreas and Biliary Tract. Sendai, Tohoku University Press, 1999, pp 203–212.
- Taki T, Goto H, Naitoh Y, Hirooka Y, Furukawa T, Hayakawa T: Diagnosis of mucin-producing tumor of the pancreas with an intraductal ultrasonographic system. J Ultrasound Med 1997;16:1–6.
- Nakamura Y, Nakazawa S, Yamao K, Yoshino J, Inui K, Kanemaki N, Wakabayasi T, Okushima K, Iwase T, Taki N, Sugiyama K, Mizutani S, Horibe Y, Imaeda Y, Hujimoto M, Hattori T, Miyoshi H: Evaluation of intraductal ultrasonography of the pancreas for intraductal papillary tumor (in Japanese with English abstract). Gastroenterol Endosc 1997;39:42–51.
- Uehara H, Nakaizumi A, Tatsuta M, Iishi H, Kitamura T, Ohigashi H, Ishikawa O, Takenaka A: Diagnosis of carcinoma in situ of the pancreas by peroral pancreatoscopy and pancreatoscopic cytology. Cancer 1997;79:454–461.
- Yamao K, Ohashi K, Nakamura T, Suzuki T, Sawaki A, Hara K, Fukutomi A, Baba T, Okubo K, Tanaka K, Moriyama I, Fukuda K, Matsumoto K, Shimizu Y: Efficacy of peroral pancreatoscopy in the diagnosis of pancreatic diseases. Gastrointest Endosc 2003;57:205–209.
- Hara T, Yamaguchi T, Ishihara T, Tsuyuguchi T, Kondo F, Kato K, Asano T, Saisho H: Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography. Gastroenterology 2002;122:34–43.
- Kobari M, Egawa S, Shibuya K, Shimamura H, Sunamura M, Takeda K, Matsuno S, Furukawa T: Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management. Arch Surg 1999;134:1131–1136.
- Terris B, Ponsot P, Paye F, Hammel P, Sauvanet A, Molas G, Bernades P, Belghiti J, Ruszniewski P, Flejou JF: Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 2000;24:1372–1377.
- Doi R, Fujimoto K, Wada M, Imamura M: Surgical management of intraductal papillary mucinous tumor of the pancreas. Surgery 2002;132:80–85.
- Matsumoto T, Aramaki M, Yada K, Hirano S, Himeno Y, Shibata K, Kawano K, Kitano S: Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas. J Clin Gastroenterol 2003;36:261–265.
- Choi BS, Kim TK, Kim AY, Kim KW, Park SW, Kim PN, Ha HK, Lee MG, Kim SC: Differential diagnosis of benign and malignant intraductal papillary mucinous tumors of the pancreas: MR cholangio-pancreatography and MR angiography. Korean J Radiol 2003;4:157–162.
- Kitagawa Y, Unger TA, Taylor S, Kozarek RA, Traverso LW: Mucus is a predictor of better prognosis and survival in patients with intraductal papillary mucinous tumor of the pancreas. J Gastrointest Surg 2003;7:12–19.
- Sugiyama M, Izumisato Y, Abe N, Masaki T, Mori T, Atomi Y: Predictive factors for malignancy in intraductal papillary-mucinous tumors of the pancreas. Br J Surg 2003;90:1244–1249.
- Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD: Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg 2004;239:788–799.
- Salvia R, Fernández-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, Pederzoli P, Warshaw AL: Main duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg 2004;239:678–687.
- Hruban RH, Takaori K, Klimstra DS, Adsay NV, Albores-Saavedra J, Biankin AV, Biankin SA, Compton C, Fukushima N, Furukawa T, Goggins M, Kato Y, Kloeppel G, Longnecker DS, Luttges J, Maitra A, Offerhaus GJ, Shimizu M, Yonezawa S: An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 2004;28:977–987.
- Compagno J, Oertel JE: Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol 1978;69:573–580.
- Izumo A, Yamaguchi K, Eguchi T, Nishiyama K, Yamamoto H, Yonemasu H, Yao T, Tanaka M, Tsuneyoshi M: Mucinous cystic tumor of the pancreas: immunohistochemical assessment of ‘ovarian-type stroma’. Oncol Rep 2003;10:515–525.
- Reddy RP, Smyrk TC, Zapiach M, Levy MJ, Pearson RK, Clain JE, Farnell MB, Sarr MG, Chari ST: Pancreatic mucinous cystic neoplasm defined by ovarian stroma: demographics, clinical features, and prevalence of cancer. Clin Gastroenterol Hepatol 2004;2:1026–1031.
- Zamboni G, Scarpa A, Bogina G, Iacono C, Bassi C, Talamini G, Sessa F, Capella, C, Solcia E, Rickaert F, Mariuzzi GM, Kloeppel G: Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors. Am J Surg Pathol 1999;23:410–422.
- Thompson LD, Becker RC, Przygodzki RM, Adair CF, Heffess CS: Mucinous cystic neoplasm (mucinous cystadenocarcinoma of low-grade malignant potential) of the pancreas: a clinicopathologic study of 130 cases. Am J Surg Pathol 1999;23:1–16.
- Wouters K, Ectors N, Van Steenbergen W, Aerts R, Driessen A, van Hoe L, Geboes K: A pancreatic mucinous cystadenoma in a man with mesenchymal stroma, expressing oestrogen and progesterone receptors. Virchows Arch 1998;432:187–189.
- Warshaw AL, Compton CC, Lewandrowski K, Cardenosa G, Mueller PR: Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Ann Surg 1990;212:432–445.
- Nakagohri T, Asano T, Kenmochi T, Urashima T, Ochiai T: Long-term surgical outcome of noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma of the pancreas. World J Surg 2002;26:1166–1169.
- Falconi M, Salvia R, Bassi C, Zamboni G, Talamini G, Pederzoli P: Clinicopathological features and treatment of intraductal papillary mucinous tumour of the pancreas. Br J Surg 2001;88:376–381.
- Sarr MG, Carpenter HA, Prabhakar LP, Orchard TF, Hughes S, van Heerden JA, DiMagno EP: Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms? Ann Surg 2000;231:205–212.
- Wilentz RE, Albores-Saavedra J, Zahurak M, Talamini MA, Yeo CJ, Cameron JL, Hruban RH: Pathologic examination accurately predicts prognosis in mucinous cystic neoplasms of the pancreas. Am J Surg Pathol 1999;23:1320–1327.
- Kaneko T, Nakao A, Inoue S, Sugimoto H, Hatsuno T, Ito A, Hirooka Y, Nagasaka T, Nakashima N: Intraoperative ultrasonography by high-resolution annular array transducer for intraductal papillary mucinous tumors of the pancreas. Surgery 2001;129:55–65.
- Kaneko T, Nakao A, Nomoto S, Furukawa T, Hirooka Y, Nakashima N, Nagasaka T: Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin-producing tumors of the pancreas. Arch Surg 1998;133:263–267.
- Fujii T, Obara T, Maguchi H, Tanno S, Ura H, Kohgo Y: Clinicopathological study of mucin-producing tumors of the pancreas: multi-centric development of carcinoma through atypical hyperplasia (in Japanese with English abstract). Suizou J Jpn Pancreatol Soc 1996;11:344–352.
- Chari S, Yadav D, Smyrk TC, DiMagno EP, Miller LJ, Massimo M, Clain JE, Norton IA, Farnell MB, Sarr MG: Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology 2002;123:1500–1507.
- Biasiutti C, Fornasa F, Venturini S, Pagnotta N, Schenal G, Procacci C: Mucinous cystic tumors; in Procacci C, Megibow AJ (eds): Imaging of the Pancreas. Cystic and Rare Tumors. Heidelberg, Springer, 2003, pp 57–74.
- Fukushima N, Mukai K: Pancreatic neoplasms with abundant mucus production: emphasis on intraductal papillary-mucinous tumors and mucinous cystic tumors. Adv Anat Pathol 1999;6:65–77.
- Itai Y, Minami M: Intraductal papillary-mucinous tumor and mucinous cystic neoplasm: CT and MR findings. Int J Gastrointest Cancer 2001;30:47–63.
- Kimura W: IHPBA in Tokyo, 2002: Surgical treatment of IPMT vs. MCT: a Japanese experience. J Hepatobiliary Pancreat Surg 2003;10:156–162.
- Maguchi H, Takahashi K, Katanuma A, Hayashi T, Yoshida A, Sakurai Y: Intraductal papillary mucinous tumor: imaging diagnosis (in Japanese with English abstract). Nippon Geka Gakkai Zasshi (J Japan Surg Soc) 2003;104:447–452.
- Solcia E, Capella C, Kloeppel G: Tumors of the Pancreas. Washington, Armed Forces Institutes of Pathology, 1997.
- Yamao K, Nakamura T, Suzuki T, Sawaki A, Hara K, Kato T, Okubo K, Matsumoto K, Shimizu Y: Endoscopic diagnosis and staging of mucinous cystic neoplasms and intraductal papillary-mucinous tumors. J Hepatobiliary Pancreat Surg. J Hep Bil Pancr Surg J Hepatobiliary Pancreat Surg 2003;10:142–146.
- Japan Pancreas Society: Classification of Pancreatic Carcinoma. ed 2, revised in English. Tokyo, Kanehara, 2002.
- Yamao K, Ohashi K, Nakamura T, Suzuki T, Watanabe Y, Shimizu Y, Nakamura Y, Ozden I: Evaluation of various imaging methods in the differential diagnosis of intraductal papillary-mucinous tumor (IPMT) of the pancreas. Hepato-Gastroenterol 2001;48:962–966.
- Wada K, Takada T, Yasuda H, Amano H, Yoshida M, Sugimoto M, Irie H: Does ‘clonal progression’ relate to the development of intraductal papillary mucinous tumors of the pancreas? J Gastrointest Surg 2004;8:289– 296.
- Lillemoe KD, Kaushal S, Cameron JL, Sohn TA, Pitt HA, Yeo CJ: Distal pancreatectomy: indications and outcomes in 235 patients. Ann Surg 1999;229:693–698.
- Warshaw AL: Conservation of the spleen with distal pancreatectomy. Arch Surg 1988;123:550–553.
- Kimura W, Inoue T, Futakawa N, Shinkai H, Han I, Muto T: Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein. Surgery 1996;120:885–890.
- Lukish JR, Rothstein JH, Petruzziello M, Kiteley R, Denobile J, Soballe P: Spleen-preserving pancreatectomy for cystic pancreatic neoplasms. Am Surg 1999;65:596–599.
- Shoup M, Brennan MF, McWhite K, Leung DH, Klimstra D, Conlon KC: The value of splenic preservation with distal pancreatectomy. Arch Surg 2002;137:164–168.
- Kobayashi G, Fujita N, Noda Y, et al: Histological features and prognosis of mucinous cystic tumors of the pancreas; in Wakui A, Yamauchi H, Ouchi K (eds): Carcinoma of the Pancreas and Biliary Tract. Sendai, Tohoku University Press, 1999, pp 213–218.
- Sugiyama M, Atomi Y: Intraductal papillary mucinous tumors of the pancreas: imaging studies and treatment strategies. Ann Surg 1998;228:685–691.
- Kimura W, Nagai H: Study of surgical anatomy for duodenum-preserving resection of the head of the pancreas. Ann Surg 1995;221:359–363.
- Hirata K, Mukaiya M, Kimura M, Ming Xion, Satoh M, Yamashiro K, Katsuramaki T, Mikami T, Dennno R: The anatomy of the pancreaticoduodenal vessels and the introduction of a new pylorus-preserving pancreaticoduodenectomy with increased vessel preservation. J Hepatobiliary Pancreat Surg 1994;1:335–341.
- Beger H, Witte C, Krass E, Bittner R: Erfahrung mit einer das Duodenum erhaltenden Pankreaskopfresektion bei chronischer Pankreatitis. Chirurg 1980;51:303–309.
- Takada T, Yasuda H, Uchiyama K, Hasegawa H: Duodenum-preserving pancreatoduodenectomy: a new technique for complete excision of the head of the pancreas with preservation of the biliary and alimentary integrity. Hepatogastroenterology 1993;40:356–359.
- Imaizumi T, Hanyu F, Suzuki M, Nakasako T, Harada N, Hatori T: Clinical experience with duodenum-preserving total resection of the head of the pancreas with pancreatico-choledochoduodenectomy. J Hepatobiliary Pancreat Surg 1995;2:38–44.
- Nakao A: Pancreatic head resection with segmental duodenectomy and preservation of the gastroduodenal artery. Hepatogastroenterology 2004;145:533–535.
- Takada T: Surgery for carcinoma of the pancreas in Japan. Past, present, and future aspects. Digestion 1999;60(suppl 1):114–119.
- Takada T, Amano H, Ammori B: A novel technique for multiple pancreatectomies: removal of uncinate process of the pancreas combined with medial pancreatectomy. J Hepatobiliary Pancreat Surg 2000;7:49–52.
- Yamaguchi K, Shimizu S, Yokohata K, Noshiro H, Chijiiwa K, Tanaka M: Ductal branch-oriented minimal pancreatectomy: two cases of successful treatment. J Hepatobiliary Pancreat Surg 1999;6:69–73.
- Thayer SP, Fernández-del Castillo C, Balcom JH, Warshaw AL: Complete dorsal pancreatectomy with preservation of the ventral pancreas: a new surgical technique. Surgery 2002;131:577–580.
- Takada T, Yasuda H, Uchiyama K, Hasegawa H, Iwagaki T, Yamakawa Y: A proposed new pancreatic classification system according to segments: operative procedure for a medial pancreatic segmentectomy. J Hepatobiliary Pancreat Surg 1994;1:322–325.
- Warshaw AL, Rattner DW, Fernandez-del Castillo C, Z’graggen K: Middle segment pancreatectomy: a novel technique for conserving pancreatic tissue. Arch Surg 1998;133:327–331.
- Yamaguchi K, Ohuchida J, Ohtsuka T, Nakano K, Tanaka M: Intraductal papillary-mucinous tumor of the pancreas concomitant with ductal carcinomas of the pancreas. Pancreatology 2002;2:484–490.
- Sugiyama M, Atomi Y: Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas. Am J Gastroenterol 1999;94:470–473.
- Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS: Intraductal papillary-mucinous neoplasms of the pancreas. An analysis of in situ and invasive carcinomas in 28 patients. Cancer 2002;94:62–77.
- Fukushima N, Mukai K, Kanai Y, Hasebe T, Shimada K, Ozaki H, Kinoshita T, Kosuge T: Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 cases. Hum Pathol 1997;28:1010–1017.
- Andea A, Sarkar F, Adsay VN: Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Pathol 2003;16:996–1006.
- Adsay NV, Merati K, Basturk O, Iacobuzio-Donahue C, Levi E, Cheng JD, Sarkar FH, Hruban RH, Klimstra DS: Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an ‘intestinal’ pathway of carcinogenesis in the pancreas. Am J Surg Pathol 2004;28:839–848.
- Brat DJ, Lillemoe KD, Yeo CJ, Warfield PB, Hruban RH: Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol 1998;22:163–169.
- Takaori K, Kobashi Y, Matsusue S, Matsui K, Yamamoto T: Clinicopathological features of pancreatic intraepithelial neoplasias and their relationship to intraductal papillary-mucinous tumors. J Hepatobiliary Pancreat Surg 2003;10:125–136.
- Biankin AV, Kench JG, Biankin SA, Lee CS, Morey AL, Dijkman FP, Coleman MJ, Sutherland RL, Henshall SM: Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence. Am J Surg Pathol 2004;28:1184–1192.
- Andea A, Cheng JD, Lauwers GY, Klimstra D, Adsay NV: Pancreatic intraepithelial neoplasia in pancreata involved by mucinous cystic neoplasia (abstract). Mod Pathol 2003;15:282A.
- Pour PM, Konishi Y, Kloppel G, Longnecker DS (eds): Atlas of Exocrine Pancreatic Tumors, Morphology, Biology, and Diagnosis with an International Guide for Tumor Classification. Tokyo, Springer, 1994, pp 265–279.
- Irie H, Yoshimitsu K, Aibe H, Tajima T, Nishie A, Nakayama T, Kakihara D, Honda H: Natural history of pancreatic intraductal papillary mucinous tumor of branch duct type: follow-up study by magnetic resonance cholangiopancreatography. J Comput Assist Tomogr 2004;28:117–122.
- Wakabayashi T, Kawaura Y, Morimoto H, Watanabe K, Toya D, Asada Y, Satomura Y, Watanabe H, Okai T, Sawabu N: Clinical management of intraductal papillary mucinous tumors of the pancreas based on imaging findings. Pancreas 2001;22:370–377.
- Yamaguchi K, Sugitani A, Chijiiwa K, Tanaka M: Intraductal papillary-mucinous tumor of the pancreas: assessing the grade of malignancy from natural history. Am Surg 2001;67:400–406.
- Obara T, Maguchi H, Saitoh Y, Itoh A, Arisato S, Ashida T, Nishino N, Ura H, Namiki M: Mucin-producing tumor of the pancreas: natural history and serial pancreatogram changes. Am J Gastroenterol 1993;88:564–569.
- Yamaguchi K, Yokohata K, Noshiro H, Chijiiwa K, Tanaka M: Mucinous cystic neoplasm of the pancreas or intraductal papillary-mucinous tumor of the pancreas. Eur J Surg 2000;166:141–148.
- Osanai M, Tanno S, Nakano Y, Koizumi K, Habiro A, Kohgo Y: Extrapancreatic neoplasms in patients with intraductal papillary mucinous tumors of the pancreas: analysis in surgical and follow-up series (in Japanese with English abstract). J Jpn Pancreas Soc 2003;18:565–569.
Masao Tanaka, MD, PhD, FACS
Department of Surgery and Oncology
Graduate School of Medical Sciences, Kyushu University
Fukuoka 812-8582 (Japan)
Tel. +81 92 642 5437, Fax +81 92 642 5457, E-Mail firstname.lastname@example.org
Published online: November 29, 2005
Number of Print Pages : 16
Number of Figures : 10, Number of Tables : 4, Number of References : 86
Vol. 6, No. 1-2, Year 2006 (Cover Date: April 2006)
Journal Editor: Urrutia, R. (Rochester, Minn.)
ISSN: 1424–3903 (print), 1424–3911 (Online)
For additional information: http://www.karger.com/PAN
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.