Eighteen patients with 22 hepatocellular carcinoma (HCC) lesions less than 2 cm in diameter were examined with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil (Lipiodol CT). Eight lesions detected at ultrasound examination of eight patients were not identified at conventional angiography, DSA, or Lipiodol CT. At histologic examination, all eight lesions were found to consist of well-differentiated carcinoma of grade I or II on the Edmondson-Steiner scale, and four had fatty change in cancer cells. Percutaneous tissue-core biopsy was indispensable in the diagnosis of well-differentiated HCC lesions that could not be diagnosed with conventional angiography, DSA, and Lipiodol CT.

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Pancreatic cancer is one of the leading causes of cancer-related mortality and has the lowest 5-year survival rate. Therefore, novel strategies are urgently required to treat pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) cells rely on enhanced lysosomal function for survival and proliferation to facilitate the degradation of contents accumulated via autophagy and macropinocytosis. Previously, we have reported that the combination of epidermal growth factor receptor/HER2 inhibitor lapatinib and sphingosine analog fingolimod (FTY720) confers a significant cytostatic effect in lung cancer cells. In the present study, the combined effects of these drugs on PDAC cell lines, BxPC-3, KP-4, PANC-1 and MIA PaCa-2, were examined. It was observed that FTY720 enhanced the lapatinib-induced cytotoxic effect and caused non-canonical and lysosome-dependent death in PDAC cells. Lapatinib and FTY720 induced lysosomal swelling and inhibited lysosomal acidification. Combination treatment with lapatinib and FTY720 increased lysosomal membrane permeability, induced mitochondrial depolarization, induced endoplasmic reticulum stress and disturbed intracellular calcium homeostasis. Additionally, the cytotoxic effect of lapatinib was enhanced by hydroxychloroquine or the CDK4/6 inhibitor abemaciclib, both of which induce lysosomal dysfunction. Collectively, these results indicated that the lysosome-targeted drug combination induces multiple organelle dysfunction and exerts a marked cytotoxic effect in PDAC cells.

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