Hepatocellular carcinoma with spontaneous regression of multiple lung metastases

Spontaneously regressed lung metastasis of hepatocellular carcinoma (HCC) in a 82-year-old Japanese man with liver cirrhosis was recorded. Multiple nodular lesions of both lungs, up to 1 cm across, were shown on chest X-ray when the clinical diagnosis of HCC was made because of the presence of a liver mass on abdominal computed tomography (CT) scan and high serum alpha-fetoprotein (AFP) value. The lung lesions which were regarded clinically as metastasis of HCC decreased in number and size 7 months later, and subsequently disappeared a further 7 months radiographically. However, the liver mass revealed no reduction on abdominal CT, despite normalization of the serum AFP value, and the patient died 7 months after the disappearance of the lung lesions. The patient refused biopsy for the liver mass and anticancerous treatment during the course of the disease. At autopsy, the liver mass, 13 cm in diameter, histologically featured moderately differentiated HCC. Only one metastasis, 0.5 cm across, was obvious in the left lower lung lobe. In addition, there were 14 minute lesions in both lungs, up to 0.2 cm across, including three with complete necrosis and 11 with histocytic reaction and fibrosis. The necrotic tissue was filled with large ghostly cells that appeared to be debris from a neoplastic tissue, regardless of no viable tumor cells among them. The clinical and autopsy findings highly suggested that the patient developed spontaneous regression of multiple lung metastases of HCC and subsequently left the very small lesions as the vestige. Thus, the histology of these lesions may exhibit a process of the regression as the sequence of events, i.e., a transition from necrosis of the metastatic HCC to its fibrosis. Presence of an effective factor(s) in relation to the regression was unclarified. There has been no reported cases with regression of the only metastasis of HCC in the literature to date.     

Transarterial embolisation of hepatocellular carcinoma with doxorubicin-eluting beads: single centre early experience

Purpose:

This is a retrospective study to evaluate the results of our early experience of using doxorubicin eluting beads (DEB) to treat patients with early and intermediate hepatocellular carcinoma (HCC).Material and methods: A cohort of 19 patients (84.2% male; 15.8% female; mean age 59.2 years ± 11.0; range, 32-80 years) with documented HCC of size 1.8-10cm (mean, 4.0cm ± 1.8 ) undergoing DEB transarterial chembolisation (TACE) was reviewed. All patients had at least one image examination (multiphase computed tomography or magnetic resonance imaging) after embolisation.

Results:

A total of 32 procedures were performed. The objective response according to the European Association for the Study of the Liver criteria was 57.9% at 1-month, 42.8% at 6-month and 50.0% at 1-year follow up. There were 4 (21.1%) treatment-related complications (1 liver abscess, 2 pancreatitis and 1 tumour rupture) which resulted in 2 deaths. One death occurred 3 weeks after second embolisation, due to ruptured pancreatic pseudocyst, giving a 5.3% 30-day mortality rate. Another patient died 2 months after embolisation caused by tumour rupture. Eight patients received radiofrequency ablation after embolisation for residual or recurrent tumours. The 1-year survival rate in the DEB TACE only group was 80% while the 1- and 2-year survival rate in the group that received radiofrequency after DEB TACE was 85.7% and 100% respectively.

Conclusion:

DEB TACE is safe and effective in select group of patients. Survival may be improved when combined with other treatment modality.     

Hepatocellular carcinoma with silent and cirrhotic non-alcoholic steatohepatitis, accompanying ectopic liver tissue attached to gallbladder

A 70-year-old man had been obese since youth. He had been treated for hypertension and diabetes mellitus. An abdominal ultrasound showed a mass in the liver. He was admitted to St Marianna University School of Medicine Hospital for further evaluation. There was no history of alcohol use, and hepatitis viral markers and autoantibodies were all negative. Several imaging studies showed overt hepatocellular carcinoma (HCC). Transcatheter arterial embolization was performed, followed by surgical resection. Histopathological examination revealed moderately differentiated HCC. The non-tumor areas had pseudolobules in a diffuse pattern similar to alcoholic cirrhosis. The histological findings in the ectopic liver tissue attached to the gallbladder, which was also resected during surgery, were that there was no cirrhosis, but fine fibrosis with inflammatory cell infiltration of sinusoids. These findings were consistent with non-alcoholic steatohepatitis (NASH). There was probably a progression of similar findings that had developed into cirrhosis. These findings confirmed a diagnosis of HCC, cirrhosis, and underlying NASH in this patient. The present case is important for investigation of the development into cirrhosis and carcinogenesis of NASH. The present case demonstrates the importance of evaluating obese patients with fatty liver for underlying NASH and ongoing follow up for development of cirrhosis and HCC.     

Surgery versus radiofrequency ablation in patients with Child- Pugh class-A/single small (≤3 cm) hepatocellular carcinoma

Background/AimsWe compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA).MethodsWe retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2–3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment.ResultsThe median follow-up period was 64.8 months (interquartile range, 0.1–162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396–1.232) (P=0.215) and 1.698 (1.777–2.448) (P=0.005), respectively.ConclusionsSR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.     

CIK细胞免疫联合TACE微创治疗原发性肝癌的研究进展

<正>原发性肝癌(即肝细胞癌,hepatocellular carcinoma,HCC)是临床常见的消化系统恶性肿瘤,近年来发病率呈现上升趋势。因其发病隐匿,早期症状不明显,绝大多数患者在确诊时已是晚期,手术切除率低,治疗主要依赖局部射频消融、动脉栓塞治疗、生物治疗及分子靶向治疗等非手术治疗。其中经导管动脉化疗栓塞(transcatheter arterial chemoemboliza-     

索拉非尼联合经皮肝动脉化疗栓塞及射频消融治疗中晚期大肝癌方案的初步探索

目的研究应用不同方案行索拉非尼联合经皮肝动脉化疗栓塞（TACE）及射频消融（RFA）（局部介入术前开始应用索拉非尼以及局部介入术后开始应用索拉非尼）治疗中晚期〉5cm肝癌的适用性及安全性,初步观察其疗效。方法 2008年11月始筛选纳入〉5cm的中晚期肝癌患者。随机分为2组,A组为先行TACE联合RFA,术后开始口服索拉非尼;B组为先口服索拉非尼1～2周,再行TACE及RFA。规律随访,观察毒副反应的发生情况及患者生存情况。结果截至2013年2月21日,A组与B组分别纳入患者15例。肝癌直径（8.9±3.1）cm,患者随访时间（27±11.8）月。两组均未发生与治疗相关的死亡,索拉非尼主要相关不良反应有手足皮肤反应（53.3%vs66.7%,P=0.710）、食欲下降（53.3%vs46.7%,P=0.999）、乏力（53.3%vs40.0%,P=0.715）以及腹泻（33.3%vs46.7%,P=0.710）等,只有1例患者出现4级的上消化道出血,两组比较差异均无统计学意义。两组患者的远期生存疗效差异无统计学意义（中位生存时间：A组31月vsB组32月,χ2=0.050,P=0.822）。结论两种联合方案在治疗中晚期大肝癌均是安全适用的,且治疗风险相当。生存分析并未显示出应用哪一种联合方案更具有优势。     

Sigmoid colon metastasis from hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major health problem worldwide, and it has a poor prognosis. Extrahepatic metastasis from HCC is not unusual, with direct invasion representing the main spreading mode. Sites that are frequently involved are the lung, bone, and lymph nodes. There are few reports of HCC invading the distant gastrointestinal tract, especially hematogenously. Herein we report a case of sigmoid colon metastasis from HCC. The patient was diagnosed with HCC and treated with transcatheter arterial chemoembolization (TACE). Eighteen months after TACE the patient presented with abdominal pain on the left lower quadrant, and a CT scan showed an enhanced mass on the sigmoid colon. Immunohistochemical staining revealed that a tumor cell was positive for polyclonal carcinoembryonic antigen and weakly positive for hepatocyte antigen, supporting the diagnosis of HCC metastasis. The patient underwent anterior resection for the metastatic HCC.     

Solitary extrahepatic intraabdominal metastasis from hepatocellular carcinoma after liver transplantation

A liver transplantation is a treatment option in selected patients with hepatocellular carcinoma (HCC). Despite the adequate selection of candidates, recurrences of HCC may still develop. Solitary extrahepatic metastasis from HCC after a liver transplantation is rare. Here we report two cases of HCC demonstrated extrahepatic recurrence to the adrenal gland and spleen, respectively, within one year after a liver transplantation. Since the treatment of solitary extrahepatic metastasis from HCC after a liver transplantation is not standardized, surgical resection was performed. In the case of HCC adrenal metastasis, innumerable intrahepatic metastases were found two months after the adrenalectomy. And 16 months after adrenalectomy, the patient expired due to tumor progression and hepatic failure. In the case of HCC splenic metastasis, postoperative radiation therapy was performed. However, two recurrent HCC nodules were found 15 months after the splenectomy and received transarterial chemoembolization (TACE). And 29 month after the splenectomy, the patient also expired as same causes of former patient.     

Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient

Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.     

Optimizing the management of intermediate-stage hepatocellular carcinoma: Current trends and prospects

Hepatocellular carcinoma (HCC) is usually accompanied by chronic liver damage, which sometimes influences the selection of HCC treatment. The Barcelona Clinic Liver Cancer (BCLC) staging system, which was first introduced in 1999, is the most commonly used worldwide. Although the intermediate-stage (BCLC stage B) includes the largest number and heterogeneous HCC patients, the recommended treatment option is transarterial chemoembolization (TACE) only. However, recent progress in radical treatments such as hepatic resection, liver transplantation, radiation therapy, and percutaneous therapy has made it possible to treat selected patients with BCLC stage B HCC. Radical treatments are expected to prolong survival time. To-date, TACE has also progressed. In addition to conventional TACE, balloon-occluded TACE and drug-eluting beads TACE are available. These new modalities of TACE will improve therapeutic efficacy and reduce adverse events. One of the most serious concerns of TACE is that repeated TACE reduces the treatment effect and induces liver function impairment. The decision on when TACE should be interrupted is complex. Many molecular targeted agents are now available, and immune checkpoint inhibitors will soon be available for HCC patients with Child-Pugh class A worldwide. Under these circumstances, in patients with TACE unsuitability, switching to molecular targeted agents before deterioration of liver function might improve the prognosis compared to repeated TACE. We should pay attention to stop TACE in TACE-unsuitable HCC patients as it can induce the deterioration of liver function.     

Hepatocellular carcinoma with worsened hypoglycemia after transarterial chemoembolization: a case report and systematic review

Non-islet cell tumor hypoglycemia (NICTH) is an extremely uncommon and serious complication of hepatocellular carcinoma (HCC). Here, we reported a case of a 47-year-old male patient with moderate to poorly differentiated HCC complicated by hypoglycemia that worsened after transarterial chemoembolization (TACE). The patient was admitted into The First Affiliated Hospital of Naval Medical University due to fatigue, nausea, dizziness and passage of tea colored urine. He was diagnosed with NICTH induced by HCC according to CT scanning and laboratory tests. TACE was used as the primary therapy but the hypoglycemia worsened afterward. Then the patient received a liver transplantation as a possible radical cure and hypoglycemia was resolved. We systematically review the management of hypoglycemia caused by HCC and the results show that patients undergoing treatment that mainly alleviate tumor burdens obtained a significantly higher response rate than patients undergoing therapies mainly regulating biologic functions (50.0% vs 27.3%). Cytoreductive surgery, TACE and radiotherapy which aimed to alleviate tumor burdens are effective therapies have great potential, but the risk of hypoglycemic deterioration requires particular attention when using these treatments, especially with TACE.     

A case of isolated metastatic hepatocellular carcinoma arising from the pelvic bone

Reports of metastatic hepatocellular carcinoma (HCC) without a primary liver tumor are rare. Here we present a case of isolated HCC that had metastasized to the pelvic bone without a primary focus. A 73-year-old man presented with severe back and right-leg pain. Radiological examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a huge mass on the pelvic bone (13×10 cm). He underwent an incisional biopsy, and the results of the subsequent histological examination were consistent with metastatic hepatocellular carcinoma. The tumor cells were positive for cytokeratin (AE1/AE3), hepatocyte paraffin 1, and glypican-3, and negative for CD56, chromogranin A, and synaptophysin on immunohistochemical staining. Examination of the liver by CT, MRI, positron-emission tomography scan, and angiography produced no evidence of a primary tumor. Radiotherapy and transarterial chemoembolization were performed on the pelvic bone, followed by systemic chemotherapy. These combination treatments resulted in tumor regression with necrotic changes. However, multiple lung metastases developed 1 year after the treatment, and the patient was treated with additional systemic chemotherapy.     

Hepatogastric fistula caused by direct invasion of hepatocellular carcinoma after transarterial chemoembolization and radiotherapy

A 63-year-old man with a history of hepatitis-B-related hepatocellular carcinoma (HCC) in the left lateral portion of the liver received repeated transcatheter arterial chemoembolization (TACE) and salvage radiotherapy. Two months after completing radiotherapy, he presented with dysphagia, epigastric pain, and a protruding abdominal mass. Computed tomography showed that the bulging mass was directly invading the adjacent stomach. Endoscopy revealed a fistula from the HCC invading the stomach. Although the size of the mass had decreased with the drainage through the fistula, and his symptoms had gradually improved, he died of cancer-related bleeding and hepatic failure. This represents a case in which an HCC invaded the stomach and caused a hepatogastric fistula after repeated TACE and salvage radiotherapy.     

CT引导下经皮无水酒精加碘油注射治疗肝癌及转移瘤化疗栓塞后残存活灶

目的评价CT引导下经皮碘化油／无水酒精瘤体多点注射治疗肝癌（PEI／PII）的临床价值。方法15例肝癌TACE后两周，对残存肿瘤行PEI，4周后增强CT／MRI评价术后疗效。结果15例20个残存活灶，12例15个病灶直径≤3cm，12个病灶完全坏死，3个病灶坏死大于75％；2例3个病灶5cm≥病灶直径〉3cm者，2个坏死范围≥75％，1个坏死范围i〉50％，1例病灶直径〉5cm，病灶坏死范围〈50％。结论TACE结合PEI／PII治疗肝癌，对于小于3cm的病灶，能更好提高疗效，有较高的临床治疗价值。     

Cytomorphology of a solitary left chest wall mass: an unusual presentation from unknown primary hepatocellular carcinoma

Hepatocellular carcinoma (HCC) may present in various ways, but only very rarely with symptoms of distant metastases or evolve from ectopic liver tissue. This report describes a case of a 62-year-old white man who was admitted for hemoptysis and a large left chest wall mass that was growing for about a year. The patient underwent Fine-needle aspiration (FNA) of the mass that revealed poorly differentiated large-cell carcinoma. A lung primary was suspected initially; however, further workup of this patient showed an elevated serum alpha-fetoprotein (AFP) level of 16,425 ng/ml. A computerized tomography (CT) scan of the abdomen showed cirrhotic liver, evidence of esophageal varices, but no evidence of a liver mass. The FNA findings were reviewed and ancillary studies were performed, including pan cytokeratin (AE1/3), Hepatocyte Paraffin 1 (HepPar-1), AFP, CD10, CD34, and polyclonal CEA. The results confirmed the diagnoses of HCC probably from occult primary or from ectopic liver tissue. The former was suggested, since serum AFP was dropped to 6,640 ng/ml following resection of the tumor. We concluded that HCC should be considered in the list of differential diagnosis of chest wall mass. HCC may present as metastatic disease from a clinically and radiologically unrecognized liver mass. FNA, coupled with ancillary studies, provides a rapid and accurate diagnostic tool in challenging cases.     

Management strategies for hepatocellular carcinoma: old certainties and new realities

Hepatocellular carcinoma (HCC) is a highly prevalent disease ranking among the ten most common cancers worldwide with increasing trend of incidence in most developed countries. The great healthcare costs and economic burden of HCC dictate proper preventive interventions as well as surveillance and screening programs to decrease disease incidence and allow early diagnosis. HCC treatment outcomes are affected by several variables, including liver function, patient’s performance status, and tumor stage. In line with the Barcelona Clinic Liver Cancer (BCLC) staging curative treatments, such as surgery or radio-frequency ablation, are indicated in early-stage HCC (BCLC-A), and the noncurative treatments are indicated in intermediate and advanced stages of HCC (BCLC-B, C). Transarterial chemoembolization (TACE) represents the treatment of choice for intermediate-stage HCC with Child–Pugh A cirrhosis, and the long-term survival after liver transplantation is inferior to that of early-stage HCCs. In advanced-stage HCC or when complete necrosis is not achieved or early recurrence after TACE develops, individualized treatments such as systemic treatment or combined radiation therapy are indicated. The increasing knowledge of the genomic landscape of HCC and the development of molecular-targeted therapies is heading toward expanding the armamentarium for HCC management.     

Transarterial chemoembolization using drug eluting beads for the treatment of hepatocellular carcinoma: Now and future

Transarterial chemoembolization (TACE) using doxorubicin-eluting beads (DEBs) have been introduced as a novel device which ensures more sustained and tumor-selective drug delivery and permanent embolization compared to conventional TACE with lipiodol. Studies highlighting the use of TACE with DEBs for the treatment of hepatocellular carcinoma (HCC) have shown similar or better results compared to conventional TACE with lipiodol. TACE with DEBs is increasingly being performed interchangeably with conventional TACE. This review assessed the characteristics, clinical outcomes and future direction of TACE with DEBs compared to conventional TACE.     

肝细胞肝癌发病过程中HBVx及COX-2的作用

目的 研究HBVx和COX-2在肝细胞肝癌发病过程中的作用.方法 145例HCC、78例肝炎后肝硬化及16例来自尸检的正常肝组织标本经病理复查后制成组织芯片,进行HE及免疫组织化学染色,评定各指标的染色指数.结果 HCC组HBVx平均阳性表达指数高于肝硬化组(P<0.01).HBVx在高、中、低分化HCC组间表达差异有统计学意义.COX-2免疫组化染色在肝硬化组表达较强;在HCC组和正常人肝细胞胞质中表达较弱.HCC组肿瘤细胞胞质中COX-2阳性表达指数低于肝硬化组(P<0.01).COX-2在高、中、低HCC组间表达差异有统计学意义.相关性分析表明145例HCC中HBVx表达与COX-2表达存在正相关(P=0.000).结论HBVx可通过调节COX-2的表达参与HCC发病过程.     

Tumor-to-tumor metastasis: Hepatocellular carcinoma metastatic to parathyroid adenoma

Tumor‐to‐tumor metastasis is a rare, but well‐recognized phenomenon. Here, we report a unique case of hepatocellular carcinoma (HCC) metastatic to parathyroid adenoma. A 53‐year‐old‐man with a history of HCC presented with hypercalcemia. It was found that he also had hyperparathyroidism with a hypoechoic mass in the lower portion of the right thyroid gland area. The patient underwent parathyroidectomy, and a mass measuring 1.5 × 1.0 cm was detected. Microscopic and immunohistochemical examination disclosed parathyroid adenoma with a focus of metastatic HCC. For the patient, it was the only distant metastasis revealed until the last follow‐up. To the best of our knowledge, this is the first reported case of tumor‐to‐tumor metastasis in which HCC is the donor.     

Hepatocellular carcinoma occurring in a young Crohn's disease patient

Reported herein is a case of hepatocellular carcinoma (HCC) occurring in a 25-year-old Japanese man who was diagnosed with Crohn's disease (CD) at 14 years of age; treatment included predonisolone, azathioprine, and infliximab. The tumor was located in right upper lobe and the size was 8 cm in diameter; histology was poorly differentiated HCC with pleomorphic cellular changes. Adjacent normal liver showed no evidence of cirrhosis or viral hepatitis. Until now, only six cases of HCC arising in patients with CD have been reported in the English-language literature. Most of these patients had early onset of CD and HCC: none had cirrhosis or virus hepatitis. Most patients had a long disease history of CD and were being medicated with several immunosuppressive agents. Some factors associated with CD might indirectly or directly be related to the development of HCC in CD patients, although the possibility that these HCC occurred coincidentally in CD patients, including the present patient, cannot be ruled out. Accumulation of cases is necessary to evaluate the relationship between CD and HCC precisely.