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  • Several mechanisms for cardiac involvement have been propoun

    2019-04-28

    Several mechanisms for cardiac involvement have been propounded as (1) direct cardiac involvement, (2) hematogenous spread, (3) lymphatic spread, (4) spreading from the venous system, such as the pulmonary vein or inferior vena cava. In cases of pericardium metastasis, most spreading routes result from direct involvement of the thoracic tumors or retrograde invasion through intrathoracic lymphatic channels. On the contrary, in cases of myocardium or epicardium metastases, the major causes are exclusively retrograde lymphatic spreading and invasion from malignancy of the pericardial fluid. Clinical manifestations of secondary tumor-associated cardiac metastases are refractory and diffuse pericardial effusion, congestive heart failure, arrhythmia, pericarditis, or cardiac tamponade. In previous studies, most cases of gastric cancer with cardiac involvement result from signet ring gastric carcinoma. Signet ring gastric carcinoma, characterized by deeper gastric wall invasion and more lymph node spreading than non-signet ring gastric carcinoma, leads to rapid intra-abdominal or peritoneal metastasis, or distant spreading. Generally, signet ring cell gastric cancer comprises approximately 10% of all gastric cancers and they are frequently observed in relatively young populations. In addition, patients with signet ring cell gastric carcinoma often present with unusual sites of metastases. Iesato et al reported two cases of signet ring cell carcinoma with breast metastases, along with a literature review. On histopathological analyses, signet-ring cell gastric carcinoma accounts for two-thirds of the cases of gastric cancer with breast metastases. Therefore, in our case, fulminant disease course and rapid visceral organ involvement such as regional/distant lymph node, cardiac, and ovarian metastases could result from this type of gastric cancer. Recently, amplification of a common gene of the human epidermal growth factor family reported in breast cancer patients, ERBB2 (HER2/neu), has been observed in advanced/metastatic gastric cancer; this gene can trigger signal transduction pathways and subsequently affect cell growth, apoptosis, metastases, and angiogenesis. However, there are several differences in the pdk 1 of the ERBB family between breast cancer and gastric cancer. In breast cancer, ERBB2/ERBB3 heterodimers have been identified to play important roles in breast cancer progression and metastatic mechanisms. On the other hand, most studies demonstrate that ERBB3 may contribute to some mechanisms of dedifferentiated gastric cancers through a common receptor, ERBB2. ERBB4 could have a dominant role in signet ring cancers. Nevertheless, most studies focus on the prognostic effects of HER2/neu. Several studies have pointed out that this marker can severe as a prognostic marker and it correlates with features of poor prognoses, such as rapid distant metastases, local recurrence, and shorter overall survival. The HER2-positive rate in gastric cancer patients is highly variable. According to previous studies, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) demonstrated different positive rates of approximately 6.8%–34.0% and 7.1%–42.6%, respectively. Most gastric cancers with HER2 overexpression or amplification are intestinal type gastric cancers and are located in the gastroesophageal junction rather than the stomach. A phase 3, open-label, randomized controlled trial (the ToGA trial) showed that co-administration of trastuzumab and chemotherapy may be an optimal therapeutic strategy in HER2-positive advanced gastric or gastro-esophageal junction cancer patients. In a cost-effectiveness analysis, therapy with trastuzumab was found to be suitable and cost effective for IHC 3+ advanced gastric cancer patients. Interestingly, the patients in these studies had relatively lower ECOG scores and fewer comorbidities despite that fact that some patients presented with advanced or metastatic gastric cancer. However, our patient presented with a high tumor burden, a fulminant disease course, and a very poor performance status. Therefore, combination therapy with trastuzumab and chemotherapy could be considered an unsuitable strategy. Her disease progressed despite administration of two cycles of this agent. In patients with a poor performance status, the effect of therapy with trastuzumab alone should be observed carefully. Further clinical trials are required to determine the effect of trastuzumab in these different populations.