Surgical Implications for Diagnosis and Treatment of Intestinal Aspergillosis in Pediatric Patients with ALL

Janina Fischer; Thorsten Simon; Axel Hamprecht; Nina Hos; Anja Möricke; Grigore Cernaianu; Lars Tharun; Bernd Gruhn; Georg Plum; Martin Dübbers

doi:10.1055/s-0037-1607194

European Journal of Pediatric Surgery, Table of Contents

Eur J Pediatr Surg 2018; 28(06): 477-483
DOI: 10.1055/s-0037-1607194

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Surgical Implications for Diagnosis and Treatment of Intestinal Aspergillosis in Pediatric Patients with ALL

Janina Fischer

¹Division of Pediatric Surgery, University Hospital of Cologne, Cologne, Germany

²Department of Pediatric Oncology, Klinikum der Universitat zu Koln Klinik und Poliklinik fur Kinder- und Jugendmedizin, Koln, Germany

,

Thorsten Simon

²Department of Pediatric Oncology, Klinikum der Universitat zu Koln Klinik und Poliklinik fur Kinder- und Jugendmedizin, Koln, Germany

,

Axel Hamprecht

³Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany

,

Nina Hos

³Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany

⁴Cluster of Excellence in Aging-associated Diseases, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany

⁵German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany

,

Anja Möricke

⁶Department of Pediatrics, Universitatsklinikum Schleswig-Holstein Campus Kiel, Kiel, Schleswig-Holstein, Germany

,

Grigore Cernaianu

¹Division of Pediatric Surgery, University Hospital of Cologne, Cologne, Germany

,

Lars Tharun

⁷Institute for Pathology, University Hospital of Schleswig Hostein-Campus Lübeck, Lübeck, Germany

,

Bernd Gruhn

⁸Department of Pediatrics, Universitatsklinikum Jena, Jena, Thüringen, Germany

,

Georg Plum

³Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany

,

Martin Dübbers

¹Division of Pediatric Surgery, University Hospital of Cologne, Cologne, Germany

› Author Affiliations

Abstract

Background The incidence of invasive aspergillosis (IA) in children with hematooncological malignancies is increasing as a result of intensive treatment, immunosuppression, and extended use of broad-spectrum antibiotics. Infection of the GI tract by Aspergillus spp. is a rare and fatal complication, which often requires surgical diagnostic and therapeutic exploration.

Objective The aim of this study was to determine the characteristics of symptomatic intestinal aspergillosis, diagnosis, treatment, and outcome of pediatric patients with an underlying hemato-oncologic disease.

Patients and Methods We analyzed 2,307 German patients with acute lymphoblastic leukemia (ALL) from age 1 to 17 years registered in the AIEOP-BFM ALL 2000 study from 2000 to 2006. All reported adverse events were assessed for symptoms of IA and retrospectively reviewed for any sign or proof of intestinal involvement of IA.

Results In this cohort, IA was reported in 30 of 2,307 patients while intestinal involvement was documented in five patients. Four of these patients had intestinal symptoms and three patients underwent explorative laparotomy. Among clinical cases with IA, gastrointestinal manifestation of IA mostly occurred in adolescent patients (10–16 years). Symptoms varied from abdominal tenderness and pain to constipation. Intestinal aspergillosis was proven by microbiological and histopathological examination and fungal infection was observed macroscopically in the jejunal lumen during surgery. Despite the extended surgery and antifungal therapy, outcome of disseminated IA with intestinal involvement remains poor.

Conclusion Surgeons should be aware of surgical complications of intestinal aspergillosis in children with hematooncological diseases requiring exploration and resection. IA is a rare event and still difficult to diagnose due to unspecific abdominal symptoms. Thus, biopsy sampling is of utmost importance to ensure diagnosis, and resection of necrotic or perforated tissue should be attempted early.

Keywords

intestinal aspergillosis - pediatric - intestinal - ulcerations

Full Text

References

References
1 Lackner M, Lass-Flörl C. Up-date on diagnostic strategies of invasive aspergillosis. Curr Pharm Des 2013; 19 (20) 3595-3614
2 Klingspor L, Saaedi B, Ljungman P, Szakos A. Epidemiology and outcomes of patients with invasive mould infections: a retrospective observational study from a single centre (2005-2009). Mycoses 2015; 58 (08) 470-477
3 Bochennek K, Hassler A, Perner C. , et al. Infectious complications in children with acute myeloid leukemia: decreased mortality in multicenter trial AML-BFM 2004. Blood Cancer J 2016; 6: e382
4 Ducassou S, Rivaud D, Auvrignon A. , et al. Invasive Fungal Infections in Pediatric Acute Myelogenous Leukemia. Pediatr Infect Dis J 2015; 34 (11) 1262-1264
5 Catalano L, Picardi M, Anzivino D, Insabato L, Notaro R, Rotoli B. Small bowel infarction by Aspergillus. Haematologica 1997; 82 (02) 182-183
6 Rosen GP, Nielsen K, Glenn S, Abelson J, Deville J, Moore TB. Invasive fungal infections in pediatric oncology patients: 11-year experience at a single institution. J Pediatr Hematol Oncol 2005; 27 (03) 135-140
7 Rubio PM, Sevilla J, González-Vicent M. , et al. Increasing incidence of invasive aspergillosis in pediatric hematology oncology patients over the last decade: a retrospective single centre study. J Pediatr Hematol Oncol 2009; 31 (09) 642-646
8 De Pauw B, Walsh TJ, Donnelly JP. , et al; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46 (12) 1813-1821
9 Möricke A, Zimmermann M, Valsecchi MG. , et al. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood 2016; 127 (17) 2101-2112
10 Conter V, Bartram CR, Valsecchi MG. , et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 2010; 115 (16) 3206-3214
11 Schrappe M, Valsecchi MG, Bartram CR. , et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood 2011; 118 (08) 2077-2084
12 Cohen R, Heffner JE. Bowel infarction as the initial manifestation of disseminated aspergillosis. Chest 1992; 101 (03) 877-879
13 Enjoji M, Ohtsukasa S, Nagano H. , et al. Localized small-bowel infarction caused by Aspergillus during chemotherapy for acute myeloid leukemia: report of a case. Surg Today 2008; 38 (05) 449-452
14 Weingrad DN, Knapper WH, Gold J, Mertelsmann R. Aspergillus Peritonitis complicating perforated appendicitis in adult acute leukemia. J Surg Oncol 1982; 19 (01) 5-8
15 Kazan E, Maertens J, Herbrecht R. , et al. A retrospective series of gut aspergillosis in haematology patients. Clin Microbiol Infect 2011; 17 (04) 588-594
16 Hayden JT, Wood KM, Pedler S, Lawson A, Skinner R. Invasive aspergillosis of the small bowel in an infant with acute myeloid leukemia and intestinal obstruction. Pediatr Hematol Oncol 2009; 26 (01) 84-91
17 Marterre Jr WF, Mong AT, Pulito AR. Locally invasive aspergillosis of the bowel. J Pediatr Surg 1992; 27 (12) 1611-1613
18 Lehrnbecher T, Becker M, Schwabe D. , et al. Primary intestinal aspergillosis after high-dose chemotherapy and autologous stem cell rescue. Pediatr Infect Dis J 2006; 25 (05) 465-466
19 Decembrino N, Zecca M, Tortorano AM. , et al. Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia. New Microbiol 2016; 39 (01) 65-69
20 Chaudhary A, Jain V, Dwivedi RS, Misra S. Invasive aspergillosis causing small bowel infarction in a patient of carcinoma breast undergoing chemotherapy. J Carcinog 2006; 5: 18
21 Castillo M. Intestinal retransplant in a patient after fungal sepsis: considerations and issues. Prog Transplant 2013; 23 (04) 368-370
22 Lehrnbecher T, Becker K, Groll AH. Current Algorithms in Fungal Diagnosis in the Immunocompromised Host. Methods Mol Biol 2017; 1508: 67-84
23 Rüchel R, Schaffrinski M, Seshan KR, Cole GT. Vital staining of fungal elements in deep-seated mycotic lesions during experimental murine mycoses using the parenterally applied optical brightener Blankophor. Med Mycol 2000; 38 (03) 231-237
24 Tarrand JJ, Lichterfeld M, Warraich I. , et al. Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination. Am J Clin Pathol 2003; 119 (06) 854-858