Lung cancer is the leading cause of cancer-related death worldwide. Compared to other types of cancer, the long-term survival rate remains poor in lung cancer [1
]. Many factors contribute to the high mortality of this cancer. One major factor is the advanced state of the lung cancer and presence of metastatic lesions by the time of diagnosis. The most frequent sites of metastasis of this tumor are brain, bone, adrenal gland and liver. All of these extrathoracic organs should be screened by imaging modalities for pretreatment evaluation [2
Liver metastasis, with its high blood flow, is frequent not only in lung cancer but also cancers of the stomach, colon, breast, etc. Primary or metastatic liver tumors sometimes cause complications. Metastatic liver tumor has been reported, for example, to cause liver failure and extrahepatic biliary obstruction [3
]. Portal hypertension is usually caused by liver cirrhosis, but portal vein invasion by hepatocellular carcinoma, by other tumors, or by tumor emboli to the vein may lead to the hypertensive state in some cases. The three major complications of portal hypertension are gastroesophageal varix, ascites, and hypersplenism. Patients with liver cirrhosis routinely undergo upper gastrointestinal endoscopy to screen for gastroesophageal varices because the first of these complications, gastroesophageal variceal hemorrhage, can be fatal. Endoscopic variceal ligation and other prophylactic endoscopic treatments are recommended for patients with gastroesophageal varices [5
The progression from chronic hepatitis to cirrhosis usually takes place over a period of years. The development of collateral circulation is accompanied by portal hypertension induced by hepatic fibrosis. Distended and engorged epigastric veins (caput medusae) are a typical sign found in physical examination, and CT scanning is a suitable evaluation for the portal venous system [6
]. Yet no features of liver cirrhosis were found in any of our examinations or in the patient's medical history. The evidence suggested that his portal circulation had changed rapidly and drastically, and the formation of gastroesophageal varix seemed to be caused subacutely by an abrupt increase of his portal vein pressure. The patient's metastatic liver tumor was the most likely cause of his portal hypertension. Diffuse hepatic sinusoidal metastases and the notable conformational changes brought about by chemotherapy might have induced the gastroesophageal varix hemorrhage by altering the hemodynamics of his portal circulation.
Recent progress in molecular targeted therapy now enables clinical oncologists to tailor therapeutic drugs to the biological profiles of the patients. The reported evidence singles out EGFR as the strongest biomarker for NSCLC and as the biomarker most predictive of prognosis. A recent clinical trial in Japan has shown that gefitinib, a well-known EGFR-tyrosine kinase inhibitor, can prolong progression-free survival and overall survival in patients positive for the EGFR mutation [7
]. The frequency of the EGFR mutation in NSCLC is high in the Japanese population, especially in adenocarcinoma histology [8
]. The Japan Cancer Society guideline recommends first-line use of gefitinib for EGFR mutation-positive patients. Bevacizumab is the monoclonal antibody against vascular endothelial growth factor (VEGF). It modifies intratumoral angiogenesis and facilitates drug delivery to tumor cells [9
]. Adding bevacizumab to cytotoxic chemotherapy may bring about a higher response rate and better overall survival than what will normally be achieved by chemotherapy without the antibody [10
]. Bevacizumab should be considered an option for patients who clear exclusion criteria such as squamous histology, etc. [11
Gefitinib shows great therapeutic efficiency in the subpopulation of so-called ‘super-responders’ [12
]. The agent generally achieves notable tumor regression and improved performance status at an early stage in super-responders. Our patient responded well not only to gefitinib, but also to bevacizumab-containing chemotherapy. Some reports argue that bevacizumab has the possibility of dramatic therapeutic effects [13
]. Our experience supports this. VEGF confers strong effects on liver sinusoidal endothelial cells as proliferative stimulation in vitro and supports the maintenance of sinusoidal endothelial cells [14
]. The organ-specific action in our patient may have reflected the discrepancy in his response, that is, the dramatic regression of his metastatic liver tumor versus the unchanging tumor volume in his lung.