Assessment of the Effectiveness of Eradication Therapy and its Predictors in Children with Helicobacter Pylori Infection
Anna Kanigowska1*, Monika Kwiatkowska1, Aneta Krogulska1 and Anna Szaflarska-Popławska2
1Department of Paediatrics, Allergology and Gastroenterology CM Bydgoszcz, NCU Torun, Poland
2Department of Pediatric Endoscopy and Gastrointestinal Function Testing CM Bydgoszcz, NCU Torun, Poland
Submission:August 12, 2021; Published:September 08, 2021
*Corresponding author: Anna Kanigowska, Department of Paediatrics, Allergology and Gastroenterology CM Bydgoszcz, NCU Torun, Poland
How to cite this article: Kanigowska A, Kwiatkowska M, Krogulska A, Szaflarska-Popławska A. Assessment of the Effectiveness of Eradication Therapy and its Predictors in Children with Helicobacter Pylori Infection. Adv Res Gastroentero Hepatol, 2021; 17(4): 555968. OI: 10.19080/ARGH.2021.17.555968.
Abstract
Helicobacter pylori (HP) is the most common bacterial infection in humans. However, recently, the effectiveness of HP treatment has fallen. The aim of this work is to evaluate the effectiveness of eradication therapy in children infected with HP and to identify the factors that may influence treatment effectiveness. A retrospective, single-centre study of 94 children, with chronic gastritis and duodenitis associated with HP infection during the period 01.01.2014 to 31.12.2016 was performed. The mean age was 11.2±4.9 years (range 2 to 18 years). Of these, 81% received 10- or 14-day triple therapy and 19% 10-day sequential therapy. Success was indicated by a correct result on the urea breath test. The influence of selected demographic and clinical parameters was analyzed, and an esophagogastroduodenoscopic and histopatological evaluation. Eradication of HP infection was achieved in 77 children (82%), 66 of whom (86.8%) were treated by the triple therapy regimen and 11 (61.1%) with sequential therapy (p=0.01). Remission was confirmed in 48 of 77 children (62.3%) treated effectively, and nine of 17 (52.9%) treated ineffectively (p=0.02). A statistically significant predictor of successful HP eradication was moderate microscopic gastritis and the use of omeprazole. Ineffective therapy was predicted by high-grade microscopic gastritis and the use of pantoprazole. The therapies currently used to treat HP infection in Poland are unsatisfactory. New treatment regimens are needed which take into account the antibiotic susceptibility of bacteria. Patient-related factors appear to be of little value in predicting treatment efficacy.
Keywords: Helicobacter pylori; Eradication in children; Urea breath test; Treatment effectiveness
Introduction
Leiomyomas are rare soft-tissue tumours of the appendix. A review of soft-tissue tumours of the large bowel found a total of 23 appendiceal leiomyomas published in the literature between 1875-19961. A single-centre case series of 101 appendiceal tumours between 1949 and 1972 included only two leiomyomas2. The most common presenting symptoms include pain, palpable abdominal mass and haemorrhage. Appendiceal leiomyosarcomas are rarer than leiomyomas and more commonly present with haemorrhage. There was no significant difference between the size of leiomyomas and leiomyosarcomas reported, with the majority of appendiceal lesions measuring less than 5cm maximal length [1]. Case reports demonstrate these lesions can be very large, with previously reported giant leiomyomas weighing up to 500 grams and 15cm maximal length [2-4].
Case Presentation
A 79-year-old female presented to Queen’s Medical Centre Emergency Department, Nottingham, UK with severe sudden onset right-sided flank pain. This pain had started suddenly the previous day and worsened overnight with one episode of vomiting. Whilst the patient described that she had generally been feeling well previously, she noted abdominal bloating in the previous two weeks. She was otherwise of minimal co-morbidity and able to live alone independently. She had a past medical history of hypertension, previous ectopic pregnancy, and previous hysterectomy. She did not take any regular medications. Blood tests demonstrated: Hb 109, from baseline of 135 in the previous year; Lactate was 1.6; WCC 7.61; Neutrophils 5.86; CRP 7. The patient was apyrexic, haemodynamically stable and observations were normal.
CT abdomen-pelvis with contrast demonstrated a 95mm rounded mixed density mass within the lower abdomen and pelvis to the right of the midline and contiguous with the appendix. Free fluid was present in the abdomen with predominantly high-density fluid in the pelvis consistent with haemoperitoneum. The radiological differential diagnosis was of a ruptured Gastrointestinal Stromal Tumour or torted fibroid (Figure 1).
The patient underwent laparotomy and appendicectomy the day after admission. Management options of angio-embolization and open surgery were considered. The patient was a Jehovah’s Witness and refused to receive exogenous blood products. This, along with the radiological suspicion of active bleeding, resulted in the decision to proceed to emergency surgery to achieve a definitive solution as promptly as possible. Although the patient had agreed to receive cell-saver autologous transfusion, the surgical team were hesitant to use this owing to the perceived risk of tumour seeding by recycling blood arising from the tumour bed. At laparotomy there was haemoperitoneum and active bleeding from the lesion. The patient had an uneventful recovery and was discharged day 5 after surgery.
The resected specimen demonstrated a well-circumscribed lesion measuring 110 x 105 x 85mm arising in the distal appendix. Its gross weight was 450 grams. On grossing, the cut surface had a whorled appearance with focal yellow degenerate areas. Histopathological examination demonstrated a spindled-cell lesion arising from the body and distal portion of the appendix. The lesion consisted of smooth muscle bundles arranged in fascicles with a whorled appearance. The stroma of the tumour showed collections of lymphoid aggregate with focal areas of necrosis. However, cytologically the lesion was bland with mild pleomorphism and mitotic activity was very low with 1 mitosis per 50 high-power fields (Figure 2A).
At the periphery of the lesion there are large ectatic vessels lying close to the subserosa. In one of the sections there was evidence of bleeding into the subserosa, probably representing the site of haemorrhage. Immunohistochemical staining revealed: Desmin (+), SMA (+), Caldesmon (+), DOG1 (-), CD34 (-), CD117 (-), S100 (-). Ki67 staining was very low. The above histological and immunohistochemical features confirmed a diagnosis of appendiceal leiomyoma (Figure 3).
Discussion
A PubMed (1950-2020) search was conducted using the following keywords: appendiceal leiomyoma OR appendix + leiomyoma OR appendicular leiomyoma OR veriform leiomyoma OR appendix + fibroid OR appendiceal fibroid OR vermiform fibroid. Six English-language case reports were found in this search [3-8]. A review of 50,000 appendicies included 830 leiomyomas, accounting for 1.66% of the tumours identified in the case series, and 632 malignant tumours [9]. The rarity of leiomyomas of the appendix compared to the rest of the large bowel is largely accounted for by the small volume of the appendix, reducing the probability of neoplastic mutation within this structure. Appendectomies, often as a consequence of acute appendicitis, decrease the percentage of the adult population with an intact appendix, thus further decreasing the incidence of neoplasms arising from this structure in the adult population.
Whilst appendicular leiomyomas presenting with haemoperitoneum have been reported, such a presentation is uncommon and many leiomyomas are often asymptomatic1. As previous reports have shown3,4, these leiomyomas can reach a very large size. In the present case, this caused mechanical compression and dilatation of the overlying subserosal vessels, leading to haemorrhage (Figure 2B).
To our knowledge, no previous reports discuss the utility of immunohistochemistry in such cases. Indeed, many of the published cases precede the widespread availability of this technique1. However, immunohistochemistry is of use in such rare cases to exclude other tumours (Table 1). The main differentials in this case are leiomyosarcoma, gastrointestinal stromal tumour (GIST) and schwannoma. Leiomyosarcoma of the appendix is less common than leiomyoma but carries a far worse prognosis1. Criteria to distinguish these tumours include degree of nuclear atypia and mitotic count. As such, ki67 may help illustrate regions of proliferation and help determine the malignant potential of the tumour. Both leiomyosarcoma and leiomyoma are positive for the smooth muscle markers SMA, desmin and caldesmon. Gastrointestinal stromal tumour (GIST) is the most common malignant mesenchymal tumour of the gastrointestinal tract [10]. Cytologically they demonstrate spindle or epithelioid cells arranged in a fascicular pattern. They characteristically express CD117, DOG1 and CD34. S100 and SMA are typically negative. Schwannomas of the appendix are very rare, with only a handful of cases reported in the literature [11]. Microscopic appearances are of interlaced spindle cells and with features of nuclear palisading, hylanised vessels and Verocay bodies. S100 staining is positive on immunohistochemistry with CD34, CD117, DOG1 and desmin typically negative.
In conclusion, we present a case of appendiceal leiomyoma presenting with acute haemorrhage. This case illustrates the need to consider soft tissue tumours of the appendix in the differential diagnosis of acute abdomen pain. Furthermore, we demonstrate the importance of immunohistochemistry in subtyping soft-tissue tumours of the appendix, as within this group of tumours there are considerably different prognoses.
References
- Aziz R, Khalifa M, Sharaf R (2015) Contaminated water as a source of Helicobacter pylori infection: a review. J Adv Res 6(4): 539-547.
- Malfertheiner P, Link A, Selgrad M (2014) Helicobacter pylori: perspectives and time trends. Nat Rev Gastroenterol Hepatol 11(10): 628-638.
- Kayali S, Aloe R, Bonaguri Ch, Gaiani F, Manfredi M, et al. (2018) Non-invasive tests for the diagnosis of Helicobacter pylori: state of the art. Acta Biomed 89(8): 58-64.
- Amaral O, Fernandes I, Veiga N, Pereira C, Chaves C, et al. (2017) Living Conditions and Helicobacter pylori in Adults. Hindawi BioMed Res. Int Article ID 9082716.
- Adu Aryee NA, Aabakken L, Dedey F, Nsaful J, Kudzi W (2016) Comparison of endoscopic based diagnosis with Helicobacter urease test for Helicobacter pylori BMC Res Notes 9(1): 421.
- Sjomina O, Pavlova J, Niv Y, Leja M (2018) Epidemiology of Helicobacter pylori Helicobacter 23: e12514.
- Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, et al. (2017) Global prevalence of Helicobacter pylori infection: systematic review and meta-analisis. Gastroenterology 153(2): 420-429.
- Kalach N, Bontems P, Raymond J (2017) Helicobacter pylori infection in children. Helicobacter 22: e12414.
- Zamani M, Ebrahimtabar F, Zamani V, Miller WH, Alizadeh Navaei R, et al. (2018) Systematic review with meta - analysis: the worldwide prevalence of Helicobacter pylori Aliment Pharmacol Ther 47(7): 869-876.
- Sabbagh P, Javanian M, Koppolu V, Vasigala VR, Ebrahimpour S (2019) Helicobacter pylori infection in children: an overview of diagnostic methods. Eur J Clin Microbiol Infect Dis 38(6): 1035-1045.
- Manfredi M, Gaiani F, Kayali S, Bizzarri B, Iuliano S, et al. (2018) How and when investigating and treating Helicobacter pylorii infection in children. Acta Biomed 89(8): 65-71.
- Łaszewicz W (2004) Research results on Helicobacter pylori Trans Humana, University Publishing House, Białystok.
- Szaflarska PA, Soroczyńska WA (2019) Prevalence of Helicobacter pylori infection among junior high school students in Grudziądz, Poland. Helicobacter 24(1): e12552.
- Leal YA, Flores LL, Garcia CLB, Cedillo RR, Torres J (2008) Antibody-based detection tests for the diagnosis of Helicobacter pylori infection in children: a meta-analysis. PLoS One 3(11): e3751.
- Jones NL, Koletzko S, Goodman K, Bontems P, Candranel S, et al. (2018) Diagnosis and treatment of Helicobacter pylori infection in children and adolescents. MP - pediatria. 5(4): 64-85.
- Leontiiadis G, Ford AC (2015) Helicobacter pylori eradication: gastric cancer prevention. Systematic review 406. BMJ Clin Evid 12: 406.
- Wang Y, Li Z, Wang L, Zhu GL, Zhao R, et al. (2018) A systematic review and meta-analysis of genotypic method for detecting antibiotics resistance in Helicobacter pylori. Helicobacter 23(2): e12467.
- Jones NL, Koletzko S, Goodman K, Bontems P, Candranel S, et. al. (2017) Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter Pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr 64: 991-1003.
- Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, et al. (2016) Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 43(4): 514-533.
- Malfertheiner P, Megraud F, O Morain CA, Gisbert JP, Kuipers EJ, et al. (2017) Management of Helicobacter Pylori Infection – The Maastricht V/Florence Consensus Report. Gut 66(1): 6-30.
- Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E (2018) Prevalence of Antibiotic Resistance in Helicobacter Pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology 155(5): 1372-1382.
- Lau ChSM, Ward A, Chamberlain RS (2016) Sequential (as opposed to simultaneous) antibiotic therapy improves Helicobacter pylori eradication in the pediatric population: a meta - analysis. Clin Pediatr (Phila) 55(7): 614-625.
- Wang Y, Zhao R, Wang B, Zhao Q, Li Z, et. al. (2018) Sequential versus concomitant therapy for treatment of Helicobacter pylori infection: an updated systematic review and meta-analysis. Eur J Clin Pharmacol 74(1): 1-13.
- Torres ZB, Lucero Y, Lagomarcino AJ, Orellana MA, George S, et al. (2017) Review: Prevalence and dynamics of Helicobacter pylori infection during childhood. Helicobacter 22(5): e12399.
- Gebeyehu E, Nigatu D, Engidawork E (2019) Helicobacter pylori eradication rate of standard triple therapy and factors affecting eradication rate at Bahir Dar city administration, Northwest Ethiopia: A prospective follow up study. PLoS One 14(6): e0217645.
- Lee JY, Kim N, Kim MS, Choi YJ, Lee JW, et al. (2014) Factors Affecting First-Line Triple Therapy of Helicobacter pylori Including CYP2C19 Genotype and Antibiotic Resistance. Dig Dis Sci 59(6): 1235-1243.
- Chang YW, Ko WJ, Oh ChH, Park YM, Oh SJ, et al. (2019) Clarithromycin resistance and female gender affect Helicobacter pylori eradication failure in chronic gastritis. Korean J Intern Med 34(5): 1022-1029.
- Yokota N, Ae R, Amenomori M, Kitagawa K, Nakamura T, et al. (2019) Clinical background factors affecting outcomes of Helicobacter pylori eradication therapy in primary care. J Gen Fam Med 20(4): 139-145.
- Jaka H, Mueller A, Kasang Ch, Mshana SE (2019) Predictors of triple therapy treatment failure among pylori infected patients attending at a tertiary hospital in Northwest Tanzania: a prospective study. BMC Infect Dis 19(1): 447.
- Georgopoulos SD, Ladas SD, Karatapanis S, Mentis A, Spiliadi C, et al. (2000) Factors that may affect treatment outcome of triple Helicobacter pylori eradication therapy with omeprazole, amoxicillin and clarithromycin. Dig Dis Sci 45(1): 63-67.