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Childhood Gastric Carcinoma

Childhood Stomach Cancer

Gastric cancer is a very common malignancy, but it tends to affect the elderly. Childhood gastric cancer is increasingly rare. Only a few dozen cases have been described of gastric adenocarcinoma, gastrointestinal stromal tumors, gastro-enteropancreatic neuroendocrine tumors, and other malignancies in the pediatric patient. The rarity of childhood gastric cancer contributes to diagnostic delays and thus, unfortunately, to a poorer outcome. In sum, patients who are diagnosed with localized disease, while metastatic gastric cancer is associated with high morbidity and mortality even in childhood.


Presentation

There is little information about the presentation of childhood gastric cancer. Small case series suggest that pediatric patients tend to present with diffuse metastatic disease and patterns of spread similar to those observed in adults [1] [2]. The most common presenting symptoms are non-specific gastrointestinal complaints, e.g., abdominal pain and distension, dysphagia, nausea, vomiting, hematemesis, and melena. These symptoms may be misrelated to peptic ulcer disease, and affected children may thus present with a medical history of a non-healing ulcer [3]. At the time of presentation, which may take place a few months after the onset of symptoms, gastric tumors may be palpable as upper abdominal masses.

Constitutional symptoms may be observed. The ongoing loss of blood may cause anemia and thus trigger pallor, fatigue, and weakness. Pernicious anemia may contribute to this process. Furthermore, patients who present with advanced-stage gastric cancer may have lost considerable amounts of weight, and they may show signs of paraneoplastic syndromes.

Weakness
  • The ongoing loss of blood may cause anemia and thus trigger pallor, fatigue, and weakness. Pernicious anemia may contribute to this process.[symptoma.com]
  • These leukemias can cause bone and joint pain, fatigue, weakness, pale skin, bleeding or bruising, fever, weight loss, and other symptoms.[cancer.org]
  • For example, a child may have: a swollen stomach, abdominal pain, and decreased appetite (if the tumor is in the abdomen) bone pain or soreness, black eyes, bruises, and pale skin (if the cancer has spread to the bones or bone marrow) weakness, numbness[kidshealth.org]
Pain
  • The majority of affected children claims non-specific gastrointestinal symptoms, such as abdominal pain and distension, swallowing difficulties, nausea, vomiting, vomiting of blood, and bloody stools.[symptoma.com]
  • It often causes bone pain that gets worse at night or with activity. It can also cause swelling in the area around the bone. Ewing sarcoma is a less common type of bone cancer, which can also cause bone pain and swelling.[cancer.org]
  • For example, a child may have: a swollen stomach, abdominal pain, and decreased appetite (if the tumor is in the abdomen) bone pain or soreness, black eyes, bruises, and pale skin (if the cancer has spread to the bones or bone marrow) weakness, numbness[kidshealth.org]
  • Check with your child’s doctor if your child has any of the following: Stomach pain. Loss of appetite. Weight loss for no known reason. Nausea. Vomiting. Constipation or diarrhea. Weakness.[emedicinehealth.com]
Anemia
  • The ongoing loss of blood may cause anemia and thus trigger pallor, fatigue, and weakness. Pernicious anemia may contribute to this process.[symptoma.com]
  • Case 2 is a 10-year-old boy, who was diagnosed with gastric cancer during investigations for anemia and nausea. Laparotomy revealed a type 3 tumor in the lesser curvature of the upper body, Stage III A.[ci.nii.ac.jp]
  • Many patients will have anemia (a lower than normal number of red blood cells), but have no signs or symptoms before the cancer spreads. Stomach cancer may cause any of the following signs and symptoms.[emedicinehealth.com]
Fatigue
  • The ongoing loss of blood may cause anemia and thus trigger pallor, fatigue, and weakness. Pernicious anemia may contribute to this process.[symptoma.com]
  • These leukemias can cause bone and joint pain, fatigue, weakness, pale skin, bleeding or bruising, fever, weight loss, and other symptoms.[cancer.org]
Fever
  • These leukemias can cause bone and joint pain, fatigue, weakness, pale skin, bleeding or bruising, fever, weight loss, and other symptoms.[cancer.org]
  • The first symptoms are often vague and may include irritability, being very tired, loss of appetite, and fever.[kidshealth.org]
Nausea
  • The majority of affected children claims non-specific gastrointestinal symptoms, such as abdominal pain and distension, swallowing difficulties, nausea, vomiting, vomiting of blood, and bloody stools.[symptoma.com]
  • Case 2 is a 10-year-old boy, who was diagnosed with gastric cancer during investigations for anemia and nausea. Laparotomy revealed a type 3 tumor in the lesser curvature of the upper body, Stage III A.[ci.nii.ac.jp]
  • Sometimes the child might have other symptoms, like fever, pain, nausea, or poor appetite. Wilms tumor accounts for about 5% of childhood cancers. For more information see Wilms Tumor.[cancer.org]
Vomiting
  • The majority of affected children claims non-specific gastrointestinal symptoms, such as abdominal pain and distension, swallowing difficulties, nausea, vomiting, vomiting of blood, and bloody stools.[symptoma.com]
  • They can cause headaches, nausea, vomiting, blurred or double vision, dizziness, seizures, trouble walking or handling objects, and other symptoms. Adults are more likely to develop tumors in upper parts of the brain.[cancer.org]
Hematemesis
  • Case 1 in an 11-year-old girl presented with hematemesis. A gastroscopic examination was performed, and a pathological diagnosis of signet ring cell carcinoma was made.[ci.nii.ac.jp]
  • ., abdominal pain and distension, dysphagia, nausea, vomiting, hematemesis, and melena. These symptoms may be misrelated to peptic ulcer disease, and affected children may thus present with a medical history of a non-healing ulcer.[symptoma.com]
Abdominal Pain
  • The majority of affected children claims non-specific gastrointestinal symptoms, such as abdominal pain and distension, swallowing difficulties, nausea, vomiting, vomiting of blood, and bloody stools.[symptoma.com]
  • For example, a child may have: a swollen stomach, abdominal pain, and decreased appetite (if the tumor is in the abdomen) bone pain or soreness, black eyes, bruises, and pale skin (if the cancer has spread to the bones or bone marrow) weakness, numbness[kidshealth.org]
Abdominal Mass
  • At the time of presentation, which may take place a few months after the onset of symptoms, gastric tumors may be palpable as upper abdominal masses. Constitutional symptoms may be observed.[symptoma.com]
Ulcer
  • These symptoms may be misrelated to peptic ulcer disease, and affected children may thus present with a medical history of a non-healing ulcer.[symptoma.com]
Suggestibility
  • Small case series suggest that pediatric patients tend to present with diffuse metastatic disease and patterns of spread similar to those observed in adults.[symptoma.com]
  • Another treatment the doctor might suggest is retinoid therapy. (Retinoids are substances that work in the body much like vitamin A.)[kidshealth.org]

Workup

The aforementioned symptoms should prompt an endoscopic examination, and biopsies should be taken from all suspect areas, be assessed histologically and immunohistochemically, and be graded. The macroscopic and microscopic appearance of malignant neoplasms of the stomach vary depending on the type of tumor, and the interested reader is referred to excellent reviews available in the literature [1] [4]. All patients with gastric cancers should routinely be tested for HER2 overexpression [4].

After the confirmation of diagnosis, imaging techniques such as positron emission tomography with fluorodeoxyglucose, magnetic resonance imaging, and/or computed tomography should be employed to determine the extension of the malignancy and to visualize any metastases. Childhood gastric cancer preferentially metastasizes to the peritoneum, liver, or lung [2]. Because the results of tumor staging are of utmost importance for the prognosis, any delay in the workup of suspected gastric cancer has to be avoided.

Due to the high probability of recurrence, patients should be included in monitoring programs even after the successful completion of therapy.

Helicobacter Pylori
  • This strategy would require comprehensive screenings for the presence of Helicobacter pylori, though.[symptoma.com]
  • The risk of stomach cancer is increased by having an infection with Helicobacter pylori (H. pylori) bacterium, which is found in the stomach. The stomach is a J-shaped organ in the upper abdomen.[emedicinehealth.com]

Treatment

There are no guidelines regarding the management of childhood gastric cancer, so regimens applied in adults are merely adapted to the pediatric patients [1]. In this context, surgery, radiation, and chemotherapy are the mainstays of treatment. Unless indicated otherwise by the type of gastric cancer [5], the complete resection of the primary tumor and its metastases should be aimed at. Total gastrectomy with lymphadenectomy is typically performed in this context and carried out with a curative intent. Patients may be prepared for surgery by applying neoadjuvant radiotherapy or chemotherapy. The latter is usually platinum-based with 5-fluorouracil. To prevent any recurrence, postoperative adjuvant chemoradiation has been recommended. In the setting of metastatic disease, both radiation and chemotherapy may be considered to provide palliation [2].

Molecular targeted therapy may complement the aforementioned therapeutic strategies but is restricted to certain types of gastric cancer and the identification of determined molecular profiles. Trastuzumab, for instance, may be used in patients with HER2-positive gastric cancer. It has been shown to improve the response rate and prolong survival times in adult patients and is expected to exert similar effects in children. However, both pediatric and adult patients are likely to develop resistance to trastazumab. Intense research is carried out to develop effective agents that are able to overcome the resistance mechanism [6].

Prognosis

The outcome largely depends on the type of gastric cancer and the tumor stage at the time of diagnosis. Those presenting with metastatic adenocarcinoma have a poor prognosis and median survival times of <6 months, while localized gastric cancer may possibly be removed in its entirety and cure may be achieved [2]. Gastrointestinal stromal tumors of the stomach, however, rarely lead to death [1].

Etiology

Childhood gastric cancer is a rare entity, with gastric adenocarcinoma accounting for the majority of cases. Other types of malignancy that may develop in the stomach are lymphoma, gastro-enteropancreatic neuroendocrine tumor, and gastrointestinal stromal tumor. Few studies have been conducted to identify the risk factors for gastric cancer in the pediatric population, so they are generally assumed to resemble those that were determined in adult patients. In summary, the following conditions may favor the development of malignancies of the stomach:

  • Adenocarcinoma is usually attributed to infections with Helicobacter pylori, to lifestyle decisions and dietary factors [7]. In children, both Helicobacter pylori and vitamin B12 deficiency have been described as possible triggers of tumor development [1] [8]. Additionally, viral pathogens such as human papillomaviruses have been related to this type of gastric cancer. Genetic polymorphisms may render individuals more susceptible to the aforementioned factors and favor the occurrence of de-novo adenocarcinoma of the stomach. Finally, hereditary polyposis syndromes predispose to this malignancy of the stomach, and it may develop after the successful treatment of gastric or non-gastric lymphoma [2] [3].
  • Gastrointestinal stromal tumors originate from the interstitial cells of Cajal, and the triggers of cancerogenesis remain unknown. The mutations underlying the malignant degeneration of the aforementioned cells are acquired, somatic mutations. Familial gastrointestinal stromal tumors are very rare, but deficiencies in the succinate dehydrogenase complex, Carney–Stratakis syndrome, and neurofibromatosis have been shown to predispose for the disease [9].
  • Gastro-enteropancreatic neuroendocrine tumors may be related to hereditary syndromes such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, and von Hippel-Lindau disease, or they may occur sporadically [10]. Little is known about those factors contributing to the development of sporadic gastric cancer of this type.
  • Other malignancies may develop in the stomach. The differential diagnosis of pediatric gastric tumors should include squamous cell carcinoma, leiomyosarcoma, hemangiosarcoma, liposarcoma, lymphoma, and teratoma with malignant transformation [1].

Gastric cancer patients developing tumors due to hereditary syndromes tend to present at younger ages than those with sporadic malignancies. Nevertheless, this "younger age" usually corresponds to early or mid-adulthood [11]. Thus, genetic conditions may play a role in the development of childhood gastric cancer, but the majority of cases does occur sporadically.

Epidemiology

Gastric cancer is the fourth most common cancer and the second most common cause of cancer-related mortality [4]. In the United States, the overall incidence of gastric cancer is currently estimated at 8 per 100,000 inhabitants, but <0.1% of these cases are diagnosed in patients aged <20 years. Accordingly, the incidence of childhood gastric cancer is extremely low. It has been specified as 0.1 per 100,000 people aged 15-19 years and was defined non-calculable for those aged <15 years [12].

In general, the incidence of gastric cancer is much higher in developing nations. In Japan and Korea, rates of 65 and 25 per 100,000 men and women, respectively, have been reported [13]. Such regional variations have mainly been related to the prevalence of Helicobacter pylori infection, which accounts for more than half of all cases worldwide. The proportion of smokers may also contribute to the likelihood of gastric cancer development, and children may not smoke but be exposed to the respective carcinogens while growing up. Epidemiological data that would allow for the confirmation of these hypotheses with regard to childhood gastric cancer are not available, though.

Sex distribution
Age distribution

Pathophysiology

The pathogenesis of sporadic childhood gastric cancer is poorly understood. Helicobacter pylori has repeatedly been proposed as a major cause of cancerogenesis in the stomach and has been isolated in several cases of childhood gastric cancer. The pathogen is known to cause atrophic gastritis and premalignant metaplasia of the gastric mucosa, thereby favoring the development of gastric cancer. According to a study conducted in Turkey, a clear correlation between the infection with Helicobacter pylori and the presence of precursor lesions can be seen from childhood on [8].

With regards to genetic conditions contributing to the development of isolated gastric cancer, acquired mutations of the proto-oncogene HER2 are among the pathophysiological events known to favor cancerogenesis. HER2 encodes for a tyrosine kinase receptor that regulates signal transduction in cell proliferation, differentiation, and survival, and HER2 overexpression has been found in up to 22% of gastric carcinomas. It is of special interest because it has been identified as a potential target of gastric cancer therapy: The administration of monoclonal antibodies directed against human epithelial growth factor receptor 2 may improve the outcome [4].

Prevention

Few recommendations can be given to reduce the incidence of childhood gastric cancer, and evidence regarding their effectiveness has yet to be provided. Because infectious agents such as Helicobacter pylori may be implicated in the development of malignancies of the stomach, infection control may prove beneficial. What's more, the early detection and eradication of Helicobacter pylori, which is mainly acquired in childhood, may provide more effective prevention of gastric cancer since the exposure to the pathogen is shorter and mucosal pathologies are milder when compared with adults [8]. This strategy would require comprehensive screenings for the presence of Helicobacter pylori, though.

More targeted screenings (and genetic analyses) are indicated to identify the affected members of families known to harbor mutations that predispose to gastric cancer. Because the age at onset varies between distinct hereditary cancer syndromes, the respective guidelines should be consulted prior to the establishment of a monitoring schedule.

Summary

Gastric cancer is one of the most common cancers worldwide, with patients presenting at a median age of 70 years [7]. Still, it is rarely seen in pediatrics: According to the SEER cancer statistics of the United States, <0.1% of all cases are diagnosed in patients aged <20 years [12]. The rarity of childhood gastric cancer implies a lack of awareness that, in combination with the usual aggressiveness of tumor growth, contributes to diagnostic delays and the frequent late-stage recognition of the malignancies. Indeed, the majority of cases are diagnosed when metastases have already formed. Symptom onset me precede the formation of metastases by weeks or months, so non-specific gastrointestinal complaints should always be taken seriously, and their causes need to be clarified.

Patient Information

Childhood gastric cancer is a rare disease. There are distinct types of childhood gastric cancer, much as in the adult patient, but only a few dozen cases of gastric adenocarcinoma, gastrointestinal stromal tumors, gastro-enteropancreatic neuroendocrine tumors, and other malignancies of the stomach have been described. The majority of affected children claims non-specific gastrointestinal symptoms, such as abdominal pain and distension, swallowing difficulties, nausea, vomiting, vomiting of blood, and bloody stools. The ongoing loss of blood may cause anemia with pallor, fatigue, and weakness. The patients tend to lose weight. The tumor may be palpable in the physical examination, but otherwise, none of the clinical findings reveals the severity of the disease.

In order to clarify the causes of the complaints, an endoscopic examination should be conducted. During this examination, the inner surface of the stomach can be evaluated, and tissue samples can be collected from any suspicious site. These samples are subsequently analyzed under the microscope and do allow for the diagnosis of childhood gastric cancer. Tumor staging is the next step in the workup: Imaging techniques such as positron emission tomography with fluorodeoxyglucose or computed tomography are employed to assess for the presence of metastases in the abdominal cavity, liver, lungs, or other organs. Tumor staging is important for the preparation of an appropriate treatment plan.

In most cases, the surgical removal of the entire tumor and any possible metastases will be the goal of therapy. It may be necessary to prepare the patient with radiation or chemotherapy for the curative intervention. On the other hand, childhood gastric cancer may be deemed unresectable, which usually indicates palliative treatment. Children who are diagnosed with early-stage gastric cancer, i.e., before the formation of metastases, have a far better prognosis than those presenting with metastatic disease. Cure may be achieved, but morbidity and mortality associated with childhood gastric cancer are high.

References

Article

  1. Ladd AP, Grosfeld JL. Gastrointestinal tumors in children and adolescents. Semin Pediatr Surg. 2006; 15(1):37-47.
  2. Subbiah V, Varadhachary G, Herzog CE, Huh WW. Gastric adenocarcinoma in children and adolescents. Pediatr Blood Cancer. 2011; 57(3):524-527.
  3. Goldthorn JF, Canizaro PC. Gastrointestinal malignancies in infancy, childhood, and adolescence. Surg Clin North Am. 1986; 66(4):845-861.
  4. Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012; 3(3):251-261.
  5. Jacquemart C, Guidi O, Etienne I, et al. Pediatric gastric lymphoma: a rare entity. J Pediatr Hematol Oncol. 2008; 30(12):984-986.
  6. Kelly CM, Janjigian YY. The genomics and therapeutics of HER2-positive gastric cancer-from trastuzumab and beyond. J Gastrointest Oncol. 2016; 7(5):750-762.
  7. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014; 23(5):700-713.
  8. Cam S. Risk of gastric cancer in children with Helicobacter pylori infection. Asian Pac J Cancer Prev. 2014; 15(22):9905-9908.
  9. Jones DH, Caracciolo JT, Hodul PJ, Strosberg JR, Coppola D, Bui MM. Familial gastrointestinal stromal tumor syndrome: report of 2 cases with KIT exon 11 mutation. Cancer Control. 2015; 22(1):102-108.
  10. Díez M, Teulé A, Salazar R. Gastroenteropancreatic neuroendocrine tumors: diagnosis and treatment. Ann Gastroenterol. 2013; 26(1):29-36.
  11. Kluijt I, Sijmons RH, Hoogerbrugge N, et al. Familial gastric cancer: guidelines for diagnosis, treatment and periodic surveillance. Fam Cancer. 2012; 11(3):363-369.
  12. Howlader N, Noone A, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2008. National Cancer Institute; Bethesda, MD: 2011.
  13. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010; 19(8):1893-1907.

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Last updated: 2019-07-11 20:36