Surgery of liver tumours

The liver is a segmental organ that allows resection through anatomically defined planes. The surgical management of an intrahepatic lesion, discovered either during investigation of hepatological symptoms or coincidentally, must involve an approach to investigation that carries a minimum risk and does not compromise subsequent excision of the lesion. Biopsy of an intrahepatic lesion found at laparotomy is essential, but attempts at early tissue diagnosis by percutaneous biopsy of operable tumours may lead to unnecessary morbidity and tumour spread. Preoperative studies often allow a firm pathological diagnosis to be made and ultrasonography, CT scanning and arteriography can be used to fully assess operability. Hepatocellular carcinoma (HCC) is the commonest primary liver cancer and is often found in association with cirrhosis and in patients with inadequate functional hepatic reserve. Surgical excision represents the only hope of cure for these patients and a 35% 5-year survival can be achieved by resection in the non-cirrhotic patient. Fibrolamellar HCC is less often associated with cirrhosis and is more often resectable with a better prognosis. Secondary tumours are often diffuse but about 5% of colorectal metastases are either solitary or confined to a resectable area of the liver. These tumours and secondary deposits from gastrointestinal endocrine tumours represent a small group of patients with potentially curable metastatic disease. Morbidity and mortality of operation depends on the extent of resection and the functional reserve of the liver. Local resections and resection for benign disease should carry no operative mortality. Major hepatic resection has a mortality of 3-5% and resection involving the structures at the hilus of the liver has an operative mortality of 10-12%. Liver transplantation in the management of neoplastic disease in the liver has yet to show any benefit over resectional surgery except where tumours have been discovered incidentally in the removed liver after transplantation for cirrhosis.     

Liver transplantation for malignant tumours

Despite considerable overall progress in human liver transplantation the results obtained in patients with malignant tumours have not improved significantly over the past years. One of the crucial questions in the ongoing controversial discussion remains the identification of tumour patients with the most favourable prognosis. In a consecutive series of 114 patients who received hepatic transplants for various malignant tumours of the liver and biliary tract, at least some factors could be shown to play a prognostic role. Regarding the histological type of tumour, fibrolamellar carcinoma, epitheloid haemangioendothelioma, and endocrine hepatic metastases seem to have a better long-term survival, whereas cholangiocellular carcinoma and other liver metastases had the worst outcome. In patients with primary liver or proximal bile duct cancer there was a significant influence of the pathological tumour stage at the time of transplantation: significant palliation or cure was almost essentially restricted to patients with early tumour stages as compared with advanced primary tumours and extrahepatic spread where early tumour recurrence developed in all recipients. Thus, the present concept for the treatment of malignant hepatobiliary tumours should include partial as well as total hepatectomy with subsequent liver replacement. In cases of non-resectable lesions or intrahepatic tumour recurrence following previous resection, liver transplantation offers the only chance for long-term survival.     

Long-term survival following resection of peritoneal implantation from hepatocellular carcinoma: a case report

This study presents a rare case of long-term survival following the resection of peritoneal implantation from hepatocellular carcinoma (HCC). A 33-year-old female patient with hepatitis B infection presented with a huge pedunculated HCC and underwent left lateral segmentectomy in 1995. She received regular follow-up and peritoneal implantation was diagnosed 30 months after hepatic resection using abdominal computed tomography due to elevated alpha-fetoprotein (AFP). Subsequently, the patient received segmental resection of jejunum and a solitary peritoneal implantation from HCC in the mesentery of the jejunum. No peritoneal carcinomatosis, direct invasion of the surrounding tissue, or lymph node involvement existed and the postoperative course was uneventful. Meanwhile, histopathological examination of the resected nodule revealed metastatic hepatocellular carcinoma. With regular follow-up with AFP, abdominal ultrasonography, and or computed tomography, no intrahepatic tumor recurrence or extrahepatic metastasis was observed. The patient survived for 90 months following hepatic resection, and survived disease free for 60 months after resection of peritoneal implantation from HCC.     

Portal venous invasion: the single most independent risk factor for immediate postoperative recurrence of hepatocellular carcinoma

Background and Aim: Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection. Methods: A total of 167 patients with HCC underwent hepatic resection; 60 had immediate postoperative recurrences (IPR group), and 107 had disease‐free survival for more than 5 years (DFS group). Variables were compared between the two groups. Results: Univariate analysis showed the following variables were significant risk factors for immediate postoperative recurrence of HCC: male sex, elevated serum aspartate aminotransferase level, greater amount of blood loss, longer operation time, worse tumor differentiation, higher tumor node metastasis stage, and presence of any of the following: intrahepatic metastasis, tumor‐rupture, portal venous invasion, or microvascular invasion. In multivariate analysis, only portal venous invasion was a significant risk factor (odds ratio = 3.2, P = 0.03, standard error = 0.5, Logistic regression analysis). Conclusions: Portal venous invasion may be the most significant risk factor for immediate postoperative recurrence of HCC. However, accurate assessment of this risk factor may require histological examination, limiting its utility as a preoperative predictor. Further research is necessary to definitively identify preoperative predictors.     

Repeated resection for extrahepatic recurrences after hepatectomy for ruptured hepatocellular carcinoma

In March 1999, a 54-year-old man with chronic hepatitis C was referred to our hospital because of ruptured hepatocellular carcinoma (HCC) located in Couinaud’s segments 4 and 8. He underwent central bisegmentectomy of the liver with partial resection of the diaphragm. After the first surgery, extrahepatic metastases were found on different occasions in the abdominal wall, thoracic cavity, and greater omentum and were all surgically resected. In February 2001, the serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level increased markedly to 19?000?mAU/l. Magnetic resonance imaging showed a massive right subphrenic tumor with invasion to the right diaphragm and posterior segment of the liver. The patient underwent en bloc resection of the tumor, diaphragm, posterior segment of the liver, and right lower pulmonary lobe. After the surgery, the PIVKA-II level rapidly decreased, and it has remained within the normal range to date. Two years after the last surgery, the patient is doing well without any extrahepatic recurrence, although small intrahepatic recurrences have been completely treated by radiofrequency ablation and transcatheter arterial chemoembolization. Ruptured HCC often exacerbates the risk of peritoneal dissemination and is usually difficult to completely resect. This is an extremely rare case of a patient who successfully underwent five repeated resections for extrahepatic recurrences after hepatectomy for ruptured HCC.     

Hepatic steatosis correlates with the postoperative recurrence of hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND: Hepatic steatosis is a prominent feature of chronic hepatitis C. Hepatic steatosis was reported recently to be a risk factor for hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). Aim: To investigate whether hepatic steatosis influences the postoperative recurrence of HCV-associated HCC. METHODS: A retrospective study was conducted in 88 patients undergoing curative resection of HCV-associated HCC. Cumulative tumour recurrence rates were compared between steatosis-positive and steatosis-negative patients, and the factors affecting intrahepatic recurrence were assessed. RESULTS: The respective tumour recurrence rates at 1, 3, and 5 years were 19%, 76%, and 92% in the steatosis-positive group, and 12%, 52%, and 60% in the steatosis-negative group. The tumour recurrence rate of the steatosis-positive group was significantly higher than that of the steatosis-negative group (P=0.02). Hepatic steatosis [relative risk (RR)=3.31, 95% confidence intervals (CIs)=1.49-7.41, P=0.003], stage of fibrosis (RR=3.17, 95% CI=1.35-7.47, P=0.008), surgical procedure (RR=0.22, 95% CI=0.076-0.64, P=0.005), number of tumours (RR=5.24, 95% CI=1.63-16.80, P=0.005), size of the largest tumour (RR=3.52, 95% CI=1.28-9.69, P=0.02), and vascular invasion (RR=2.72, 95% CI=1.32-5.59, P=0.007) were independent factors for tumour recurrence rate by multivariate analysis. CONCLUSIONS: Hepatic steatosis is a useful predictor of postoperative recurrence of HCV-related HCC.     

Double primary liver cancer (intrahepatic cholangiocarcinoma and hepatocellular carcinoma) in a patient with hepatitis C virus-related cirrhosis

We herein report a rare case of double primary liver cancer, consisting of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). A 67-year-old Japanese man with hepatitis C virus-related liver cirrhosis was diagnosed with multiple HCC in S7 and S8 of the liver. We performed a hepatic resection of S7 and S8. The liver tumors in S7 and S8 were pathologically diagnosed as HCC and ICC, respectively. Multiple recurrence of the HCC found 7 years after the surgery was successfully treated with transcatheter arterial chemoembolization. Subsequently, this patient has been doing well, without HCC recurrence. Double primary liver cancer is very rare, and only 21 resected cases have been reported, including that in our patient. We reviewed at all cases in the Japanese- and English-language literature to investigate the clinicopathological features. Our literature review revealed that the present patient is the longest survivor among patients who have undergone hepatectomy for double primary liver cancer.     

HBcrAg is a predictor of post‐treatment recurrence of hepatocellular carcinoma during antiviral therapy

Background/Aims: The recurrence rate of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is high even in patients receiving curative therapy. In this study, we analysed the risk factors for tumour recurrence after curative therapy for HBV‐related HCC while under treatment with nucleot(s)ide analogues (NAs) by measuring serum HBcrAg and intrahepatic covalently closed circular DNA (cccDNA) levels to elucidate the viral status associated with HCC recurrence. Methods: We enrolled 55 patients who developed HCC during NA therapy and underwent either curative resection or percutaneous ablation for HCC. Results: Hepatocellular carcinoma recurred in 21 (38%) of the patients over a period of 2.2 (range, 0.2–7.4) years. In multivariate analysis, serum HBcrAg levels ≥4.8log U/ml at the time of HCC diagnosis (hazard ratio, 8.96; 95% confidential interval, 1.94–41.4) and portal vein invasion (3.94, 1.25–12.4) were independent factors for HCC recurrence. The recurrence‐free survival rates of the high cccDNA group were significantly lower than those of the low cccDNA group only in patients who underwent resection (P=0.0438). A positive correlation (P=0.028; r=0.479) was observed between the intrahepatic cccDNA and the serum HBcrAg levels at the incidence of HCC. Conclusion: HBcrAg is a predictor of the post‐treatment recurrence of HCC during antiviral therapy. Serum HBcrAg and intrahepatic cccDNA suppression by NAs may be important to prevent HCC recurrence.     

Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma

We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma (HCC) complicating hepatitis B virus (HBV) cirrhosis. In 2001 (12 years after liver transplantation), he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCC metastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater than that of those who do not receive immunosuppressive therapy.     

Adrenal metastasis from hepatocellular carcinoma without intrahepatic recurrence after hepatic resection

Although the adrenal gland is a common site of metastasis from hepatocellular carcinoma (HCC), adrenal metastases are rarely seen in clinical practice because of its lower metastatic potential compared to the other malignancies. Adrenal metastases usually were detected at the time of diagnosis of primary HCC or simultaneously with intrahepatic recurrence after curative management of HCC. It is very rare that only metastatic HCC is detected without evidence of intrahepatic recurrence. Hereby, we report two cases of adrenal metastasis from HCC without intrahepatic recurrence after hepatic resection.     

Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection

Background

Intrahepatic recurrence is a significant problem for patients who have undergone a hepatic resection for hepatocellular carcinoma (HCC). The objective of the present study was to identify risk factors and evaluate the management of early and late recurrence of solitary HCC after curative resection.

Methods

Included in this study were 816 patients with solitary HCC who underwent a curative partial hepatectomy. Intrahepatic recurrence in these patients was followed up retrospectively. Prognosis and therapy for the recurrence were investigated and analysed.

Results

Early and late intrahepatic recurrence occurred in 423 patients and 199 patients, respectively. Multivariate analysis showed that a tumour diameter >5 cm, the absence of a tumour capsule and the presence of microvascular invasion were correlated with early recurrence, whereas cirrhosis and alpha-fetal protein >400 μg/l were independent risk factors contributing to late recurrence. The 5-year survival of HCC patients with early recurrence was significantly lower than that of patients with late recurrence. Further curative treatment for intrahepatic recurrence offered a 5-year overall survival of 56.0%, which was better than alternative management.

Conclusion

Early and late recurrences of solitary HCC after curative resection are associated with different predictive factors. The time to recurrence and further curative treatment after recurrence were the best predictors of survival post recurrence.     

Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma

We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma (HCC) complicating hepatitis B virus (HBV) cirrhosis. In 2001 (12 years after liver transplantation), he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCCmetastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater thanthat of those who do not receive immunosuppressive therapy.     

Hepatocellular carcinoma: surgical indications and results

Hepatocellular carcinoma (HCC) is a tumour of increasing incidence that usually arises in cirrhotic liver. Untreated, the prognosis is grim and the only curative treatment is surgical resection. The practical application of segmental surgery to the liver together with the use of ultrasound and other imaging techniques, patient selection criteria and improvements in perioperative technique and postoperative care have contributed to better results in hepatic surgery. Today, less than 10% mortality for resection of cirrhotic livers, with up to 50% 5-year survival rates are to be expected. However, the limits of resection for cure: intrahepatic recurrence makes stringent follow-up necessary. In this way the available modalities of treatment can be applied so as to improve survival. Herein, a current 'state-of-the-art' of surgical indications and results for HCC is given.     

Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma

To assess intrahepatic metastasis (IM) and multicentric occurrence (MO) after initial treatment of small hepatocellular carcinomas (HCC) < or = 2 cm in diameter, we performed clinical and pathological studies in 112 patients who underwent percutaneous ethanol injection therapy (PEIT) or hepatic resection for HCC from January 1985 to December 1994. Patients with intrahepatic recurrences were classified into two groups based on the type of recurrence: the IM group (n = 29, 50.9%) and the MO group (n = 28, 49.1%). Overall recurrence rates after initial treatment were 23.7% at 1 year, 64.5% at 3 years, and 76.1% at 5 years. In patients with IM, the majority of intrahepatic recurrences were observed within 3 years of initial treatment and the primary HCC lesions were closely related to the degree of tumor cell differentiation. Alternatively, intrahepatic recurrences occurred throughout the follow-up period in patients with MO, and the evidence of underlying liver disease (anti-HCV [antibody to hepatitis C virus] positive) and elevated serum alfa-fetoprotein (AFP) concentrations were closely associated with intrahepatic recurrence. Prognoses following additional treatment in MO group patients were superior to those in IM group patients. These results suggest that differentiation between IM and MO in patients with HCC is important for understanding the development and biological behavior of the tumor. That is, the early detection of intrahepatic recurrence and the institution of appropriate additional therapy (PEIT or hepatic resection) may prolong survival in patients with MO.(Hepatology 1997 Jan;25(1):87-92)     

Risk factors of intrahepatic recurrence after curative resection of hepatocellular carcinoma

BACKGROUND/AIMS: Although the risk factors for the development of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC) have been widely studied, little attention has been given to the prognostic factors affecting such patients. METHODOLOGY: Intrahepatic recurrence occurred in 105 (56%) of 188 patients who underwent curative hepatic resection of HCC and were discharged from the hospital. Among them, 17 (16%) also had simultaneous extrahepatic recurrence. Independent prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that presence of extrahepatic recurrence, hepatitis B, and non-surgical treatments for recurrence were independent predictors of poor overall survival after initial hepatic resection or after recurrence. Risk factors of extrahepatic recurrence were young age, solitary and large HCC, high hepatitis activity, and large amount of intraoperative blood loss and blood transfusion. CONCLUSIONS: Survival of patients with intrahepatic recurrent HCC after resection should be stratified by the type of recurrence, type of hepatitis, and type of treatment for recurrence.     

Long-term surviving patient with inferior vena cava tumor thrombus and extrahepatic metastasis after spontaneous ruptured hepatocellular carcinoma

We present a case of long-term survival in a patient with inferior vena cava tumor thrombus (IVCTT) and extrahepatic metastasis after resection for spontaneous ruptured hepatocellular carcinoma (HCC). The patient was a 73-year-old Japanese man previously diagnosed with chronic hepatitis B. He was referred to our emergency room and diagnosed with spontaneous ruptured HCC. The patient was immediately treated with transcatheter arterial embolization, and we then performed second-stage hepatic resection 50 days later. Although des-gamma-carboxy prothrombin was reduced to a normal level after hepatectomy, it gradually increased and computed tomography showed a disseminated tumor in the diaphragm near S2 of the liver with IVCTT and right atrium tumor thrombus. Recurrent HCC was treated with monthly transcatheter arterial infusion chemotherapy (TAI) and conformal radiotherapy (RT) of 40 Gy. After TAI and RT procedures, the disseminated tumor and IVCTT completely disappeared. Four years after TAI and RT procedures, the tumors were well controlled with no local recurrence. About 6−7 years after spontaneous ruptured HCC, lung metastasis and spleen metastasis were detected and resected, respectively. The patient is still alive and doing well over 7 years after spontaneous ruptured HCC.     

Successful selective internal radiotherapy (SIRT) in a patient with a malignant solid pseudopapillary pancreatic neoplasm (SPN)

Solid pseudopapillary neoplasms of the pancreas (SPNs, Gruber-Frantz-Tumor) are a rare entity representing 1–5% of all exocrine pancreatic tumors. The pseudocystic lesions preferentially affect young females <30 years, are mostly benign (～90%) and normally present with unspecific symptoms.We describe the case of a 16-years-old Asian woman that was initially diagnosed with an SPN in the pancreatic head with mesenterial and hepatic metastases. After diagnosis, an extensive tumor resection was performed including pyloric-preserving pancreatic head resection followed by sequential resection of all hepatic metastases. After the patient was diagnosed with a hepatic recurrence and high intrahepatic tumor load, we chose a multimodal procedure and performed a selective internal radiotherapy (SIRT). Four years after SIRT and 10 years after initial diagnosis of metastatic SPN, the patient is in a good condition without any evidence for hepatic recurrence.This case represents a rare clinical course of a malignant and invasive SPN with an exceptionally long survival despite of high initial tumor burden. The selective internal radiotherapy is a suitable approach for inducing long-term remissions of the strongly vascularized liver metastases.     

Efficacy of major hepatic resection for large hepatocellular carcinoma

BACKGROUND/AIMS: A large hepatocellular carcinoma (HCC) generally carries a poor prognosis despite curative hepatic resection. However, some cases have had good outcomes without recurrences. In this study, we investigated the factors which predicted a good prognosis. METHODOLOGY: Sixty-six patients with large HCC greater than 5 cm who underwent curative hepatic resections were divided into two groups. There were 55 patients who had recurrences within 5 years after surgery (group A) and 11 patients who did not have recurrences at the fifth year after surgery (group B). We compared the clinicopathological features between the two groups. RESULTS: No differences were seen in the pre-operative liver function tests and the incidence of histological cirrhosis. The incidence of positive rate of histological recurrence factors, such as intrahepatic metastasis and incomplete surgical margins, was significantly less in group B. Five (45%) and 10 (91%) of 11 patients in group B underwent pre-operative portal vein embolization and major hepatic resection, respectively, while 10 (18%) and 29 (53%) of 55 patients in group A underwent these procedures (p < 0.05). CONCLUSIONS: In order to increase tumor-free survival rates for patients with large HCC greater than 5 cm, major hepatic resection after portal vein embolization with complete surgical margins should be performed.     

Hepatocellular carcinoma in non-cirrhotic liver: A reappraisal

Although not frequently, hepatocellular carcinoma (HCC) can ensue in a non-cirrhotic liver. As compared to cirrhotic HCC, this kind of tumour has some peculiarities, such as: (a) a lower male preponderance and a bimodal age distribution; (b) a lower prevalence of the three main risk factors (hepatitis B and C virus infections and alcohol abuse), with an increased prevalence of other etiologic factors, such as exposure to genotoxic substances and sex hormones, inherited diseases, genetic mutations; (c) a more advanced tumour stage at the time of diagnosis, as it is usually detected due to the occurrence of cancer-related symptoms, outside any scheduled surveillance program; (d) a much higher amenability to hepatic resection, due to the low risk of liver failure even after extended parenchymal mutilation; (e) overall and disease-free survivals after resection of non-advanced tumours (meeting the Milano criteria) comparable to that obtained with liver transplantation in cirrhotic patients carrying an early tumour; (f) overall survival strictly dependent on tumour burden (and its recurrence) and barely influenced by liver function.     

Prognostic factors after recurrence of resected hepatocellular carcinoma associated with hepatitis C virus

To clarify the variables related to survival after recurrence of resected hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV), we studied 17 clinicopathological factors in 99 patients with recurrence of HCC associated with HCV infection after hepatic resection. The 1-, 3-, and 5-year survival rates after first resection in these patients were 91%, 81%, and 49%, while after recurrence they were 81%, 51%, and 29%, respectively. Multivariate analysis showed that the following six variables were independent prognostic factors after recurrence: platelet count, albumin level, bilirubin level, number of hepatic lesions, distant metastasis, and any treatment at recurrence. A correlation between second hepatic resection (SHR) and liver function tests was seen in regard to albumin and total bilirubin values at recurrence. Indeed, hepatic function and progression of intrahepatic tumors at recurrence were significant prognostic factors after recurrence of HCC associated with HCV infection, while any treatment at recurrence was also a significant prognostic factor. Therefore, in order to improve prognosis after recurrence, we should actively treat the recurrent hepatic lesions whenever possible.