nach oben

Current Gastroenterology Reports

Erschienen in:

01.12.2019 | Pediatric Gastroenterology (S Orenstein and S Khan, Section Editors)

Pediatric Intestinal Pseudo-obstruction in the Era of Genetic Sequencing

verfasst von: Heidi E. Gamboa, Manu Sood

Erschienen in: Current Gastroenterology Reports | Ausgabe 12/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

The purpose of this review is to discuss current knowledge on pediatric intestinal pseudo-obstruction. We will also review new mutations that have been identified through advancement in genetic testing, allowing for a better understanding of the underlying mechanisms of intestinal dysmotility and potential etiologies.

Recent Findings

With the advancements in genetic testing, new mutations have been identified in the diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), a disorder leading to pediatric pseudo-obstruction. MYLK, LMOD1, MYL9, and MYH11 encode for various proteins within smooth muscle cells; abnormalities within these proteins lead to abnormal intestinal smooth muscle contractions.

Summary

Chronic intestinal pseudo-obstruction (CIPO) is defined by symptoms of bowel obstruction in the absence of a lumen-occluding lesion. CIPO is a heterogeneous group of disorders caused by abnormalities in the enteric neurons, intestinal smooth muscle, and/or the interstitial cells of Cajal (ICC). Symptoms can be non-specific and etiologies include both primary and secondary causes of CIPO that contribute to the delay in recognizing this condition and making the correct diagnosis. Chronic intestinal pseudo-obstruction has been recognized in both adults and children with fundamental differences in the etiology, symptom onset, clinical features and natural history of this disorder. For this reason, it has been considered a separate entity referred to as pediatric intestinal pseudo-obstruction (PIPO).

Rudolph CD, Hyman PE, Altschuler SM, Christensen J, Colletti RB, Cucchiara S, et al. Diagnosis and treatment of chronic intestinal pseudo-obstruction in children: report of consensus workshop. J Pediatr Gastroenterol Nutr. 1997;24:102–12.PubMed

Thapar N, Saliakellis E, Benninga MA, Borrelli O, Curry J, Faure C, et al. Paediatric intestinal pseudo-obstruction: evidence and consensus-based recommendations from an ESPGHAN-Led Expert Group. J Pediatr Gastroenterol Nutr. 2018;66:991–1019.PubMed

Dudley HA, Sinclair IS, McLAREN IF, McNAIR TJ, Newsam JE. Intestinal pseudo-obstruction. J R Coll Surg Edinb. 1958;3:206–17.PubMed

Byrne WJ, Cipel L, Euler AR, Halpin TC, Ament ME. Chronic idiopathic intestinal pseudo-obstruction syndrome in children--clinical characteristics and prognosis. J Pediatr. 1977;90:585–9.PubMed

Kapur RP, Robertson SP, Hannibal MC, Finn LS, Morgan T, van Kogelenberg M, et al. Diffuse abnormal layering of small intestinal smooth muscle is present in patients with FLNA mutations and x-linked intestinal pseudo-obstruction. Am J Surg Pathol. 2010;34:1528–43.PubMed

North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Motility Resources. [Internet]. [cited 2019 Sep 13]. https://members.naspghan.org/NASPGHANMembers/Professional_Education/Motility_Resources.aspx. Accessed 20 Aug 2019

Di Lorenzo C. Pseudo-obstruction: current approaches. Gastroenterology. 1999;116:980–7.PubMed

Muto M, Matsufuji H, Tomomasa T, Nakajima A, Kawahara H, Ida S, et al. Pediatric chronic intestinal pseudo-obstruction is a rare, serious, and intractable disease: a report of a nationwide survey in Japan. J Pediatr Surg. 2014;49:1799–803.PubMed

Pingault V, Girard M, Bondurand N, Dorkins H, Van Maldergem L, Mowat D, et al. SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism. Hum Genet. 2002;111:198–206.PubMed

10.

Van Goethem G, Schwartz M, Löfgren A, Dermaut B, Van Broeckhoven C, Vissing J. Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. Eur J Hum Genet EJHG. 2003;11:547–9.PubMed

11.

Giordano C, Powell H, Leopizzi M, De Curtis M, Travaglini C, Sebastiani M, Gallo P, et al. Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to POLG1 mutations. Neurology. 2009;72:1103–5.PubMedPubMedCentral

12.

Gargiulo A, Auricchio R, Barone MV, Cotugno G, Reardon W, Milla PJ, et al. Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Am J Hum Genet. 2007;80:751–8.PubMedPubMedCentral

13.

Bott L, Boute O, Mention K, Vinchon M, Boman F, Gottrand F. Congenital idiopathic intestinal pseudo-obstruction and hydrocephalus with stenosis of the aqueduct of sylvius. Am J Med Genet A. 2004;130A:84–7.PubMed

14.

Milunsky A, Baldwin C, Zhang X, Primack D, Curnow A, Milunsky J. Diagnosis of chronic intestinal pseudo-obstruction and megacystis by sequencing the ACTG2 gene. J Pediatr Gastroenterol Nutr. 2017;65:384–7.PubMedPubMedCentral

15.

•• Dong W, Baldwin C, Choi J, Milunsky JM, Zhang J, Bilguvar K, Lifton RP, et al. Identification of a dominant MYH11 causal variant in chronic intestinal pseudo‐obstruction: results of whole‐exome sequencing. Clin Genet. 2019;96:473–7. Through whole exome sequencing, additional gene mutations affecting smooth muscle contractility were identified; this expanded our understanding of intestinal pseudo-obstruction etiologies.PubMed

16.

Gauthier J, Ouled Amar Bencheikh B, Hamdan FF, Harrison SM, Baker LA, Couture F, et al. A homozygous loss-of-function variant in MYH11 in a case with megacystis-microcolon-intestinal hypoperistalsis syndrome. Eur J Hum Genet EJHG. 2015;23:1266–8.PubMed

17.

Wang Q, Zhang J, Wang H, Feng Q, Luo F, Xie J. Compound heterozygous variants in MYH11 underlie autosomal recessive megacystis-microcolon-intestinal hypoperistalsis syndrome in a Chinese family. J Hum Genet. 2019;64:1067–73.PubMedPubMedCentral

18.

Halim D, Brosens E, Muller F, Wangler MF, Beaudet AL, Lupski JR, et al. Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome. Am J Hum Genet. 2017;101:123–9.PubMedPubMedCentral

19.

Halim D, Wilson MP, Oliver D, Brosens E, Verheij JBGM, Han Y, et al. Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice. Proc Natl Acad Sci U S A. 2017;114:E2739–47.PubMedPubMedCentral

20.

Moreno CA, Sobreira N, Pugh E, Zhang P, Steel G, Torres FR, et al. Homozygous deletion in MYL9 expands the molecular basis of megacystis-microcolon-intestinal hypoperistalsis syndrome. Eur J Hum Genet EJHG. 2018;26:669–75.PubMed

21.

Qualia CM, Brown MR, Ryan CK, Rossi TM. Oral mucosal neuromas leading to the diagnosis of multiple endocrine neoplasia type 2B in a child with intestinal pseudo-obstruction. Gastroenterol Hepatol. 2007;3:208–11.

22.

Grobmyer SR, Guillem JG, O’Riordain DS, Woodruff JM, Shriver C, Brennan MF. Colonic manifestations of multiple endocrine neoplasia type 2B: report of four cases. Dis Colon Rectum. 1999;42:1216–9.PubMed

23.

Nishino I, Spinazzola A, Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999;283:689–92.PubMed

24.

Bonora E, Bianco F, Cordeddu L, Bamshad M, Francescatto L, Dowless D, et al. Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction. Gastroenterology. 2015;148:771–782.e11.PubMedPubMedCentral

25.

• Chetaille P, Preuss C, Burkhard S, Côté J-M, Houde C, Castilloux J, et al. Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nat Genet. 2014;46:1245–9 This study describes a new syndrome called chronic atrial and intestinal dysrhythmia, an autosomal recessive form of intestinal pseudo-obstruction.PubMed

26.

Haas S, Bindl L, Fischer H-P. Autoimmune enteric leiomyositis: a rare cause of chronic intestinal pseudo-obstruction with specific morphological features. Hum Pathol. 2005;36:576–80.PubMed

27.

Ruuska TH, Karikoski R, Smith VV, Milla PJ. Acquired myopathic intestinal pseudo-obstruction may be due to autoimmune enteric leiomyositis. Gastroenterology. 2002;122:1133–9.PubMed

28.

Schäppi MG, Smith VV, Milla PJ, Lindley KJ. Eosinophilic myenteric ganglionitis is associated with functional intestinal obstruction. Gut. 2003;52:752–5.PubMedPubMedCentral

29.

Ooms AHAG, Verheij J, Hulst JM, Vlot J, van der Starre C, de Ridder L, et al. Eosinophilic myenteric ganglionitis as a cause of chronic intestinal pseudo-obstruction. Virchows Arch Int J Pathol. 2012;460:123–7.

30.

De Giorgio R, Camilleri M. Human enteric neuropathies: morphology and molecular pathology. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2004;16:515–31.

31.

Wildhaber B, Niggli F, Stallmach T, Willi U, Stauffer UG, Sacher P. Intestinal pseudoobstruction as a paraneoplastic syndrome in ganglioneuroblastoma. Eur J Pediatr Surg Off J Austrian Assoc Pediatr Surg Al Z Kinderchir. 2002;12:429–31.

32.

Smith VV, Gregson N, Foggensteiner L, Neale G, Milla PJ. Acquired intestinal aganglionosis and circulating autoantibodies without neoplasia or other neural involvement. Gastroenterology. 1997;112:1366–71.PubMed

33.

Meneghelli UG. Chagasic enteropathy. Rev Soc Bras Med Trop. 2004;37:252–60.PubMed

34.

Whitehouse FR, Kernohan JW. Myenteric plexus in congenital megacolon; study of 11 cases. Arch Intern Med Chic Ill 1908. 1948;82:75–111.

35.

Schäppi MG, Staiano A, Milla PJ, Smith VV, Dias JA, Heuschkel R, et al. A practical guide for the diagnosis of primary enteric nervous system disorders. J Pediatr Gastroenterol Nutr. 2013;57:677–86.PubMed

36.

Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, et al. The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. Gut. 2010;59:882–7.PubMed

37.

Heneyke S, Smith VV, Spitz L, Milla PJ. Chronic intestinal pseudo-obstruction: treatment and long term follow up of 44 patients. Arch Dis Child. 1999;81:21–7.PubMedPubMedCentral

38.

King SK, Sutcliffe JR, Hutson JM. Laparoscopic seromuscular colonic biopsies: a surgeon’s experience. J Pediatr Surg. 2005;40:381–4.PubMed

39.

Knowles CH, Veress B, Tornblom H, Wallace S, Paraskeva P, Darzi A, et al. Safety and diagnostic yield of laparoscopically assisted full-thickness bowel biospy. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2008;20:774–9.

40.

Furness JB. The enteric nervous system. Malden: Blackwell Pub; 2006.

41.

Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. 2012;9:286–94.PubMed

42.

Faure C, Di Lorenzo C, Thapar N. Pediatric neurogastroenterology: gastrointestinal motility and functional disorders in children [Internet]. New York: Humana Press; 2013 [cited 2019 Sep 13]. Available from:. https://doi.org/10.1007/978-1-60761-709-9.CrossRef

43.

Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, et al. Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group. Acta Neuropathol (Berl). 2009;118:271–301.

44.

Wood JD. Enteric nervous system (the brain-in-the-gut). San Rafael: Morgan & Claypool; 2011.

45.

Fell JM, Smith VV, Milla PJ. Infantile chronic idiopathic intestinal pseudo-obstruction: the role of small intestinal manometry as a diagnostic tool and prognostic indicator. Gut. 1996;39:306–11.PubMedPubMedCentral

46.

Sanders KM, Kito Y, Hwang SJ, Ward SM. Regulation of gastrointestinal smooth muscle function by interstitial cells. Physiol Bethesda Md. 2016;31:316–26.

47.

Farrugia G. Interstitial cells of Cajal in health and disease. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2008;20(Suppl 1):54–63.

48.

Feldstein AE, Miller SM, El-Youssef M, Rodeberg D, Lindor NM, Burgart LJ, et al. Chronic intestinal pseudoobstruction associated with altered interstitial cells of cajal networks. J Pediatr Gastroenterol Nutr. 2003;36:492–7.PubMed

49.

Isozaki K, Hirota S, Miyagawa J, Taniguchi M, Shinomura Y, Matsuzawa Y. Deficiency of c-kit+ cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol. 1997;92:332–4.PubMed

50.

Kenny SE, Vanderwinden JM, Rintala RJ, Connell MG, Lloyd DA, Vanderhaegen JJ, et al. Delayed maturation of the interstitial cells of Cajal: a new diagnosis for transient neonatal pseudoobstruction. Report of two cases. J Pediatr Surg. 1998;33:94–8.PubMed

51.

Yamazaki-Nakashimada MA, Rodriguez-Jurado R, Ortega-Salgado A, Gutierrez-Hernández A, García-Pavon-Osorio S, Hernandez-Bautista V. Intestinal pseudoobstruction associated with eosinophilic enteritis as the initial presentation of systemic lupus erythematosus in children. J Pediatr Gastroenterol Nutr. 2009;48:482–6.PubMed

52.

Yadak R, Breur M, Bugiani M. Gastrointestinal dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal. Orphanet J Rare Dis. 2019;14:33.PubMedPubMedCentral

53.

Mousa H, Hyman PE, Cocjin J, Flores AF, Di Lorenzo C. Long-term outcome of congenital intestinal pseudoobstruction. Dig Dis Sci. 2002;47:2298–305.PubMed

54.

Faure C, Goulet O, Ategbo S, Breton A, Tounian P, Ginies JL, et al. Chronic intestinal pseudoobstruction syndrome: clinical analysis, outcome, and prognosis in 105 children. French-Speaking Group of Pediatric Gastroenterology. Dig Dis Sci. 1999;44:953–9.PubMed

55.

Vargas JH, Sachs P, Ament ME. Chronic intestinal pseudo-obstruction syndrome in pediatrics. Results of a national survey by members of the North American Society of Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. 1988;7:323–32.PubMed

56.

Hyman PE, Bursch B, Beck D, DiLorenzo C, Zeltzer LK. Discriminating pediatric condition falsification from chronic intestinal pseudo-obstruction in toddlers. Child Maltreat. 2002;7:132–7.PubMed

57.

Granata C, Puri P. Megacystis-microcolon-intestinal hypoperistalsis syndrome. J Pediatr Gastroenterol Nutr. 1997;25:12–9.PubMed

58.

Hyman PE, McDiarmid SV, Napolitano J, Abrams CE, Tomomasa T. Antroduodenal motility in children with chronic intestinal pseudo-obstruction. J Pediatr. 1988;112:899–905.PubMed

59.

Camilleri M. Jejunal manometry in distal subacute mechanical obstruction: significance of prolonged simultaneous contractions. Gut. 1989;30:468–75.PubMedPubMedCentral

60.

Cucchiara S, Borrelli O, Salvia G, Iula VD, Fecarotta S, Gaudiello G, et al. A normal gastrointestinal motility excludes chronic intestinal pseudoobstruction in children. Dig Dis Sci. 2000;45:258–64.PubMed

61.

Sigurdsson L, Reyes J, Kocoshis SA, Mazariegos G, Abu-Elmagd KM, Bueno J, et al. Intestinal transplantation in children with chronic intestinal pseudo-obstruction. Gut. 1999;45:570–4.PubMedPubMedCentral

62.

Connor FL, Di Lorenzo C. Chronic intestinal pseudo-obstruction: assessment and management. Gastroenterology. 2006;130:S29–36.PubMed

63.

Mazziotti MV, Langer JC. Laparoscopic full-thickness intestinal biopsies in children. J Pediatr Gastroenterol Nutr. 2001;33:54–7.PubMed

64.

Youssef NN, Barksdale E Jr, Griffiths JM, Flores AF, Di Lorenzo C. Management of intractable constipation with antegrade enemas in neurologically intact children. J Pediatr Gastroenterol Nutr. 2002;34:402–5.PubMed

65.

Di Lorenzo C, Flores AF, Tomomasa T, Hyman PE. Effect of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms. Dig Dis Sci. 1994;39:1399–404.PubMed

66.

Di Lorenzo C, Lucanto C, Flores AF, Idries S, Hyman PE. Effect of octreotide on gastrointestinal motility in children with functional gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. 1998;27:508–12.PubMed

67.

Ambartsumyan L, Flores A, Nurko S, Rodriguez L. Utility of octreotide in advancing enteral feeds in children with chronic intestinal pseudo-obstruction. Paediatr Drugs. 2016;18:387–92.PubMed

68.

Gomez R, Fernandez S, Aspirot A, Punati J, Skaggs B, Mousa H, et al. Effect of amoxicillin/clavulanate on gastrointestinal motility in children. J Pediatr Gastroenterol Nutr. 2012;54:780–4.PubMed

69.

Di Lorenzo C, Reddy SN, Villanueva-Meyer J, Mena I, Martin S, Hyman PE. Cisapride in children with chronic intestinal pseudoobstruction. An acute, double-blind, crossover, placebo-controlled trial. Gastroenterology. 1991;101:1564–70.PubMed

70.

Hyman PE, Di Lorenzo C, McAdams L, Flores AF, Tomomasa T, Garvey TQ. Predicting the clinical response to cisapride in children with chronic intestinal pseudo-obstruction. Am J Gastroenterol. 1993;88:832–6.PubMed

71.

Giudicessi JR, Ackerman MJ, Camilleri M. Cardiovascular safety of prokinetic agents: a focus on drug-induced arrhythmias. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2018;30:e13302.

72.

Manini ML, Camilleri M, Grothe R, Di Lorenzo C. Application of pyridostigmine in pediatric gastrointestinal motility disorders: a case series. Paediatr Drugs. 2018;20:173–80.PubMed

73.

Husebye E. Gastrointestinal motility disorders and bacterial overgrowth. J Intern Med. 1995;237:419–27.PubMed

74.

Barkin JA, Keihanian T, Barkin JS, Antequera CM, Moshiree B. Preferential usage of rifaximin for the treatment of hydrogen-positive smallintestinal bacterial overgrowth. Rev Gastroenterol Peru Organo Of Soc Gastroenterol Peru. 2019;39:111–5.

75.

Lu W, Xiao Y, Huang J, Lu L, Tao Y, Yan W, et al. Causes and prognosis of chronic intestinal pseudo-obstruction in 48 subjects: a 10-year retrospective case series. Medicine (Baltimore). 2018;97:e12150.

76.

Prapaitrakool S, Hollmann MW, Wartenberg HC, Preckel B, Brugger S. Use of buprenorphine in children with chronic pseudoobstruction syndrome: case series and review of literature. Clin J Pain. 2012;28:722–5.PubMed

77.

Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for functional gastrointestinal disorders (disorders of gut−brain interaction): a Rome Foundation working team report. Gastroenterology. 2018;154:1140–71.PubMed

78.

Rosner H, Rubin L, Kestenbaum A. Gabapentin adjunctive therapy in neuropathic pain states. Clin J Pain. 1996;12:56–8.PubMed

79.

Altaf MA, Werlin SL, Sato TT, Rudolph CD, Sood MR. Colonic volvulus in children with intestinal motility disorders. J Pediatr Gastroenterol Nutr. 2009;49:59–62.PubMed

80.

Hanbali A, Rasheed W, Peedikayil MC, Boholega S, Alzahrani HA. Mitochondrial neurogastrointestinal encephalomyopathy syndrome treated with stem cell transplant: a case series and literature review. Exp Clin Transplant Off J Middle East Soc Organ Transplant. 2018;16:773–8.

81.

Lao OB, Healey PJ, Perkins JD, Horslen S, Reyes JD, Goldin AB. Outcomes in children after intestinal transplant. PEDIATRICS. 2010;125:e550–8.PubMedPubMedCentral

82.

Schwankovsky L, Mousa H, Rowhani A, DI Lorenzo C, Hyman PE. Quality of life outcomes in congenital chronic intestinal pseudo-obstruction. Dig Dis Sci. 2002;47:1965–8.PubMed

Titel: Pediatric Intestinal Pseudo-obstruction in the Era of Genetic Sequencing
verfasst von: Heidi E. Gamboa
Manu Sood
Publikationsdatum: 01.12.2019
Verlag: Springer US
Erschienen in: Current Gastroenterology Reports / Ausgabe 12/2019
Print ISSN: 1522-8037
Elektronische ISSN: 1534-312X
DOI: https://doi.org/10.1007/s11894-019-0737-y

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

So sicher sind Tattoos: Neue Daten zur Risikobewertung

22.05.2024 Melanom Nachrichten

Das größte medizinische Problem bei Tattoos bleiben allergische Reaktionen. Melanome werden dadurch offensichtlich nicht gefördert, die Farbpigmente könnten aber andere Tumoren begünstigen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2019

Proton Pump Inhibitors in the Elderly, Balancing Risk and Benefit: an Age-Old Problem

Tips for the Budding Esophagologist

Controversy in Nutrition Recommendations for Short Bowel Syndrome: How Type of SBS Impacts Response

Principles and Practice of Oral Rehydration

EUS-Guided Portal Venous Sampling of Circulating Tumor Cells