Case 1
An 84-year old man with chronic hepatitis C and liver cirrhosis was referred to our outpatient clinic for the evaluation of HCC, previously treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). Following disease relapse, a wedge resection of two nodules in hepatic segments VI and VII was performed in December 2008. Histological examination confirmed HCC grade III (Edmondson scoring), with necrosis and microscopic vascular thrombosis.
In September 2009, magnetic resonance imaging (MRI) showed millimetric disease relapse in hepatic segments V, II, III, and I, and a 21 × 9 mm adenopathy at the hepatic hilum (Fig. 1a, b). A new resection was scheduled but was not carried out following the detection by intra-operative ultrasound (US) of a right portal branch neoplastic thrombosis. In December 2009, serum alpha-fetoprotein (AFP) was 1504 ng/mL. In January 2010, as a consequence of disease metastasis, systemic treatment with metronomic capecitabine (500 mg twice daily) was continuously administered according to a previously described protocol [6]. The therapy was well tolerated. After 1 month, serum AFP decreased to 643 ng/mL, and 3 months later, had drastically decreased to 7 ng/mL. At the same time, a marked reduction in liver lesion size was observed by MRI, evaluated as a partial response according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) [19]. In August 2010, computer tomography (CT) scanning showed a single hypodense lesion of 13 mm in hepatic segment II without any other liver lesions, and that enlarged abdominal lymph nodes were stable and neoplastic thrombosis was not detected. Given the presence of a single lesion, the possibility of residual disease ablation was explored using hepatic contrast-enhanced ultrasound. Two suspicious lesions for HCC were detected in hepatic segments II and III, without a typical contrastographic appearance. The lesions were submitted to needle biopsy, and histological analysis identified a nodule of low-grade dysplasia in segment II and micro and macronodular cirrhosis with light activity in segment III. The patient underwent metronomic capecitabine until July 2013 when, considering the sustained CR, treatment was discontinued and the patient entered a follow-up program. The final MRI (February 2017, Fig. 1c, d) confirmed the CR. To date, the patient is alive and in good health.
Case 2
A 66-year old man had multiple liver lesions involving approximately 70% of the right liver, multiple nodules in the left lobe, and a right portal thrombosis in the setting of non-alcoholic steatohepatitis (CT scan in August 2012, Fig. 2a, b). Positron emission tomography (PET) with 2-(fluorine-18)-fluoro-2-deoxy-d-glucose (FDG-PET) identified bone metastases in the proximal portion of the right femur, in the right ischial tuberosity, in the left acetabulum, in the left scapula, and in the third left costal arch. Moreover, a PET with (11)C-choline confirmed the hepatic and skeletal lesions and identified other metastases in the pelvic bones, rachis, and ribs. In October 2012, serum AFP was 1909 ng/mL. Considering the typical contrastographic pattern of the liver lesion by CT scanning and the elevated AFP level, a diagnosis of HCC was made according to European Association for the Study of the Liver (EASL) guidelines [20].
In December 2012, the patient started systemic treatment with sorafenib 800 mg/bid. Ten days later, the treatment was discontinued because of G3 skin toxicity (Stevens–Johnson syndrome). In January 2013, the patient started metronomic capecitabine (500 mg twice daily, continuous administration), which was well-tolerated. In March 2013, a new CT scan showed a reduction in the number and size of the liver lesions with significant intralesional necrotic areas. Subsequent FDG-PET scanning (April 2013) showed the complete absence of pathological areas and, in parallel, AFP level had fallen to 3.3 ng/mL. In July 2013, a needle biopsy of the principal hepatic lesion evidenced fibrous connective tissue with histiocytic inflammation without tumour cells. An abdominal US scan (January 2014) revealed the presence of a single hypoechoic lesion of 1.4 × 1.3 cm. In December 2014, CT scanning showed a further size reduction of the hypodense hepatic lesion without vascular components, and it was therefore decided to discontinue treatment in the same month. CT and US images, supported by histological patterns, showed a necrotic lesion with gradual resolution (Fig. 2c, d). In the most recent US scan (September 2017), no hepatic lesion was detected and serum AFP was 3.6 ng/mL. The patient is currently alive and in excellent health.
Case 3
A 70-year-old man with hepatitis C virus cirrhosis was diagnosed with binodular HCC in Jul 2006 and treated with RFA and percutaneous ethanol injection (PEI). From March 2008 to March 2015, the patient experienced multiple tumour recurrences, which were managed using locoregional techniques (RFA, PEI, and one course of TACE). The patient came to our attention in October 2015 following HCC progression in the VIII segment associated with an invasion of the inferior vena cava and neoplastic pulmonary embolization. Serum AFP was 18,622 ng/mL. Systemic therapy with sorafenib was started at dosage of 400 mg/die, given the patient’s poor clinical condition, and increased to 600 mg/die after 10 days. The patient started experiencing severe fatigue, diarrhoea, and dizziness, which prompted a reduction in dosage to 400 mg/die in November 2015. In February 2016, following radiological progression (tumoural invasion of the right and median hepatic veins and enlargement of the neoplastic thrombus in the inferior cava vein) and a sharp increase in serum AFP (47,137 ng/mL), the patient was switched to capecitabine therapy (500 mg twice daily, continuous administration). CT scanning performed every 3 months showed the progressive reduction of pulmonary metastases, recanalization of the median hepatic vein, and progressive improvement in inferior cava vein invasion. Moreover, the tumour mass showed a complete devascularisation (Fig. 3a, b). Serum AFP levels decreased to 4583 ng/mL in May 2016, 5.5 ng/mL in September 2016, 2.5 ng/mL in November 2016, and 1.5 ng/mL in October 2017.
At the time of writing, the patient is in good clinical condition and continues to receive capecitabine treatment (500 mg bid), complaining only of modest fatigue.