Simultaneous Injection of Autologous Mononuclear Cells with TACE in HCC Patients; Preliminary Study

Background

The discovery of the pluripotent stem cells made the prospect of cell therapy and tissue regeneration a clinical reality, especially with the evidence of contribution of the stem cells of bone marrow origin in hepatic regeneration. Infusion of bone marrow stem cells before trans-arterial chemoembolization may help to increase liver volume and consequently increase hepatic reserve in patients with HCC, and this may improve the outcome of this procedure.

Materials and Methods

Four Child B class patients with unresectable hepatocellular carcinoma treated by transarterial chemoembolization were injected with autologous bone marrow mononuclear layer containing stem cell in the hepatic artery feeding the contralateral lobe of the liver in the same session, follow-up of the patients was done by doing liver profile and CT liver volumetry before the surgery and 3 months later.

Results

We observed that patients receiving stem cell therapy simultaneously with TACE had shown a significant improvement in biological and volumetric parameters of liver function compared to those historically reported of patients receiving TACE only who usually shows deterioration of liver parameters.

Conclusion

BMC infusion into the hepatic artery synchronized with TACE for patients with chronic liver disease complicated with HCC is safe, feasible, and demonstrated an improvement in both biological and radiological volumetric parameters.     

Laparoscopic hepatectomy for liver neoplasms in 15 cases

Objective

The aim of our study was to retrospectively analyze 15 patients’ clinical materials with laparoscopic resection of liver neoplasms.

Methods

From December 2007, a total of 15 patients with liver neoplasms were performed with laparoscopic hepatectomy, and their clinical materials, perioperative dates, postoperative complications, postoperative recovery and short-term curative effects were analyzed and summarized respectively.

Results

Laparoscopic hepatectomy (LH) were performed in 15 patients, including 1 case underwent laparoscopic hepatic left lobectomy, 1 case of left lateral hepatectomy, 13 cases of partial liver resection. Fourteen cases of total laparoscopic liver resections for liver neoplasms, 1 case of hand-assisted laparoscopic liver resection of the tumor, there was no conversion to open approach. Of the 15 patients with liver neoplasms, 13 cases of hepatic neoplasms with the maximum diameter was 8 cm × 8 cm × 9 cm, 9 cases of the borderline micro hepatocellular carcinoma (MHCC) with the diameter not more than 2 cm, 3 cases of hepatic benign tumor. The mean operation time was (120 ± 30) min, and the intraoperative average hemorrhage was 100 mL, beginning to eat and get out of bed following 1–2 days of operation. The average postoperative hospitalization was 8 days, WBC, ALT, AST, albumin, bilirubin returned to normal after one week of operation. There were no postoperative complications such as hemorrhage, bile leakage or air embolism etc. Twelve patients with HCC were confirmed by postoperative pathology, 1 case of liver smooth muscle lipoma, 2 case of hepatic hemangioma. By one year of followed-up in 12 cases of HCC, the longest survival was 38 months, and no recurrence or death, 1 year survival rate was 100%.

Conclusion

Among the choice of cases, the advantages of LH for liver neoplasms compared with open surgery were less trauma, faster recovery and less blood loss. it is safe and effective for choosing a reasonable surgical indication, especially for peripheral micro hepatocellular carcinoma.     

Histological liver injury and surgical outcome after FOLFOX followed by a hepatectomy for colorectal liver metastases in Japanese patients

Background

This study was performed to clarify the influence of preoperative chemotherapy on liver function and the correlation between histological hepatic injury and the postoperative outcome in patients with colorectal liver metastases who underwent a hepatic resection.

Methods

Twenty-seven patients who underwent a hepatic resection for colorectal liver metastases were included. Fifteen patients with initially unresectable colorectal liver metastases who were able to undergo a tumor resection after FOLFOX (oxaliplatin plus fluorouracil and leucovorin, with a mean number of 7.7 cycles) were compared to 12 patients who underwent a hepatectomy with no preoperative chemotherapy. The postoperative mortality, morbidity, changes in liver function tests, and pathology of the resected liver were examined.

Results

Preoperative FOLFOX therapy was significantly associated with the macroscopic appearance of oxaliplatin-associated blue liver (p = 0.02), and a tendency toward sinusoidal dilatation (33.3% in the FOLFOX group versus 8.3% in the no-chemotherapy group, p = 0.056). Preoperative liver function tests showed that the albumin and indocyanine green retention rate at 15 min (ICG-R15) test values were significantly worse after FOLFOX therapy; however, intraoperative events, postoperative liver function test values, and morbidity rates were similar in the two groups. There was no postoperative mortality in any of the patients.

Conclusions

Although preoperative FOLFOX administration in patients with colorectal liver metastases caused macroscopic blue liver, microscopic sinusoidal dilatationin the liver parenchyma, and a significant decrease in liver function, there was no increase in the morbidity and mortality rates, in comparison to findings in patients without preoperative chemotherapy.     

Anterior Versus Conventional Approach for Resection of Large Right Lobe Hepatocellular Carcinoma

Purpose

In this study, we aim to report the efficacy of using the anterior approach (AA) versus the conventional approach (CA), in surgical resection for large hepatocellular carcinoma (HCC) (≥7 cm) of the right hepatic lobe in terms of surgical and long-term outcomes.

Materials and Methods

Between 2000 and 2006, 138 consecutive patients who underwent hepatic resection with curative intent for large right lobe HCC ≥7 cm were identified from a retrospective database. The 40 patients who had AA were compared with the remaining 98 patients who had CA. Clinicopathological features and surgical results were analyzed and prognostic factors were evaluated by multivariate analysis.

Results

There was no significant difference between the two groups as regards clinical, laboratory, and pathological parameters. The operative results had shown a comparable proportion of patients who experienced massive operative blood loss and postoperative complications in the two groups. The AA group had a lower recurrence rate (P = 0·015), better disease-free survival (DFS) (P = 0·001), and overall survival than the CA group. Our study identified that AA is a prognostic factor of both overall survival and disease-free survival for large HCC ≥7 cm.

Conclusion

The AA is a safe and effective technique for right hepatic resection for large HCC and achieves more advantageous long survival outcome over the CA.

     

A Case of Explosive Progression of Hepatocellular Carcinoma in a Patient with Common Variable Immunodeficiency (CVID)

Objective

While it is well known that patients with common variable immunodeficiency (CVID) are predisposed to various malignancies, primarily non-Hodgkin’s lymphoma and gastric carcinomas, to our knowledge no cases of hepatocellular carcinoma have been reported in the absence of preexisting liver disease.

Method and Results

We report a 50-year-old male patient with CVID with a B- and T-cell deficiency. The patient was on prophylactic intravenous gammaglobulin and had received several years earlier a course of rituximab for an autoimmune disorder. He had no history of hepatitis. The patient developed a rapidly progressing hepatocellular carcinoma within 3 to 4 weeks.

Conclusions

Although patients with CVID are predisposed to malignancies such as lymphoma and adenocarcinoma of the stomach, rapidly progressive hepatocellular carcinoma in the absence of any preexisting liver disease has not been described.     

Multi-institutional phase II study on the feasibility of liver resection following preoperative mFOLFOX6 therapy for resectable liver metastases from colorectal cancers

Background

Although liver resection combined with preoperative chemotherapy is expected to improve outcomes of patients with resectable colorectal liver metastasis (CRLM), there is as yet insufficient clinical evidence supporting the efficacy of preoperative systemic chemotherapy. The aim of this phase II study was to assess the feasibility and efficacy of preoperative FOLFOX systemic chemotherapy for patients with initially resectable CRLM.

Methods

A prospective multi-institutional phase II study was conducted to evaluate the feasibility and efficacy of preoperative chemotherapy for resectable CRLM (ClinicalTrials.gov identifier number NCT00594529). Patients were scheduled to receive 6 cycles of mFOLFOX6 therapy before liver surgery. The primary endpoint was the macroscopic curative resection rate.

Results

A total of 30 patients were included in this study. Two patients who were diagnosed with hepatocellular and intrahepatic cholangiocellular carcinoma based on pathology were excluded from the analysis. More than half of the patients (57 %) had solitary liver metastasis. The completion rate of preoperative chemotherapy was 64.3 % and the response rate was 53.6 %. Two patients were unable to proceed to liver resections due to disease progression and severe postoperative complications following primary tumor resection. Macroscopic curative resection was obtained in 89.3 % of eligible patients. Postoperative mortality and severe complication (≥Gr. 3) rates were 0 and 11 %, respectively. The 3-year overall and progression-free survival rates were 81.9 and 47.4 %, respectively.

Conclusion

Our phase II study demonstrated the feasibility of liver resection combined with preoperative mFOLFOX6 therapy in patients with initially resectable CRLM. Further study is warranted to address the oncological effects of preoperative chemotherapy.

     

Solid Focal Liver Lesions: Dynamic and Late Enhancement Patterns with the Dual Phase Contrast Agent Gadobenate Dimeglumine

Introduction

The purpose of this paper is to illustrate contrast enhancement patterns of solid focal liver lesions on dynamic and late phase imaging with gadobenate dimeglumine (Gd-BOPTA).

Imaging Findings

Unenhanced T2- and T1-weighted, dynamic T1-weighted (arterial, portal-venous, and equilibrium) and late phase (1-3 h) Gd-BOPTA-enhanced MR imaging of different focal liver lesions (nodular regenerative hyperplasia, hepatic adenoma, liver adenomatosis, hepatocellular carcinoma, peripheral cholangiocarcinoma, hypervascular metastases, and hypovascular metastases) are shown. Dynamic imaging was performed using GRE T1-w sequences after the bolus injection of 0.1 mmol/kg Gd-BOPTA; late-phase imaging was obtained at 1-3 h after contrast injection.

Conclusions

Dynamic imaging with Gd-BOPTA provides the same information as with conventional gadolinium-based extracellular contrast agents, while late-phase imaging gives additional information for lesion identification and characterization.     

Radiologic Complete Response with Sirolimus and Sorafenib in a Hepatocellular Carcinoma Patient who Relapsed After Orthotopic Liver Transplantation

Background

No standard therapies have been established for the treatment of recurrent hepatocellular carcinoma (HCC) after liver transplantation.

Discussion

Sirolimus is a mTOR inhibitor which has been used as an immunosuppressive medication in patients who are at high risk of tumor reoccurrence after liver transplantation. Sorafenib is a multikinase inhibitor approved for the treatment of advanced HCC. However the role of sorafenib in patients with HCC reoccurrence after liver transplantation is unclear.

Results

Combination of sirolimus and sorafenib appears to have synergistic effect when treating HCC in preclinical settings. We report a case of a post-liver transplant patient treated with sorafenib and sirolimus for hepatic HCC recurrence who exhibited complete radiologic response after 5 months of therapy.     

Fibrolamellar Hepatocellular Carcinoma: a Case Report with Distinct Radiological Features

Introduction

We report a rare case of a 23-year-old male who presented with abdominal discomfort for 15 days. An ultrasound was performed which showed a hypoechoic, heterogenous mass in the left lobe of the liver and distended portal vein, followed by further investigation with computed tomography (CT), MRI, and MRA. Serum alpha-fetoprotein was not elevated and hepatitis B antigen was negative.

Methods

CT scan depicted a nodular mass in left liver lobe with occlusion of both the central part and the two main branches of intrahepatic portal vein.

Result

Biopsy of the liver mass led to a diagnosis of fibrolamellar hepatocellular carcinoma.

Conclusion

Fibrolamellar carcinoma is an uncommon variant of hepatocellular carcinoma. The diagnosis is suggested by radiographic studies and is confirmed by histological examination.     

Remnant liver volume-based predictors of postoperative liver dysfunction after hepatectomy: analysis of 625 consecutive patients from a single institution

Background

During hepatic resection, accurate estimation of remnant liver volume and hepatic function is crucial for avoiding postoperative liver failure. The purpose of this study was to identify preoperative factors related to postoperative liver dysfunction according to the percentage of future liver remnant volume (%FLR).

Methods

A total of 625 patients who underwent hepatectomy were enrolled in this study. Total bilirubin level >50 μmol/L and/or prothrombin time index <50 % on postoperative day 5 were used as criteria for postoperative liver dysfunction (PLD). Patients were classified into 3 groups according to the %FLR: 35–60 (n = 116), 60–80 (n = 157), and >80 (n = 351). Multivariate logistic regression analysis was performed to identify factors related to postoperative liver dysfunction in each group.

Results

Among the patients with 35–80 %FLR, the morbidity and mortality rates were significantly higher in patients with PLD than in patients without PLD. There was no postoperative death in patients with >80 %FLR . Multivariate analysis showed that PLD was associated with receptor index (LHL15) ≤0.93 (odds ratio [OR] = 7.96) in patients with 35–60 %FLR. The sensitivity and specificity for PLD were 87.5 and 96.1 %, respectively. In patients with 60–80 %FLR, PLD was associated with platelet count <10.0 × 10⁴/mL (OR = 6.12). The sensitivity and specificity for PLD were 73.3 and 96.2 %, respectively.

Conclusion

LHL15 ≤0.93 and platelet count <10.0 × 10⁴/mL are pivotal indicators for predicting PLD in patients with 35–60 %FLR and 60–80 %FLR, respectively.     

Postoperative liver volume was accurately predicted by a medical image three dimensional visualization system in hepatectomy for liver cancer

Background

Liver cancer is the second most common cause of cancer death worldwide. The hepatectomy is the most effective and the only potentially curative treatment for patients with resectable neoplasm. Precisely preoperative assessment of remnant liver volume is essential in preventing postoperative liver failure. The aim of our study is to report our experience of using a medical image three dimensional (3D) visualization system (MI-3DVS), which was developed by our team, in assisting hepatectomy for patients with liver cancer.

Isolated Skull Base Metastasis as the First Manifestation of Hepatocellular Carcinoma—A Rare Case Report with Review of Literature

Introduction

Hepatocellular carcinoma rarely metastasizes to skull base.

Case Report

We report an extremely rare case of solitary skull base metastasis without metastasis to any other site, with right third, fourth, and sixth cranial nerve palsy as the initial manifestation of the disease.

Discussion

The biopsy specimen of skull base lytic lesion suggested metastatic hepatocellular carcinoma. Subsequent examination revealed a large mass involving superior segment of right lobe of liver, which was confirmed as hepatocellular carcinoma on histopathological examination.

Conclusion

Until now, there have been only 24 cases of hepatocellular carcinoma metastasizing to skull base cited in literature. We report here an unusual case of solitary skull base metastasis from hepatocellular carcinoma prior to the diagnosis of primary tumor.     

Zelltransplantationen zur Regeneration und Funktionswiederherstellung vor und nach onkologischen Operationen

Background

Cell transplantation provides the unique possibility to preoperatively optimize organ function or to re-establish organ function after oncological resection. Transplantation of autologous islets of Langerhans after pancreatic resection and transplantation of hematopoietic stem cells (HSC) or mesenchymal stromal cells (MSC) to optimize liver regeneration before and after liver resection are important examples of this therapy.

Results

The transplantation of autologous islets of Langerhans is an internationally well-established procedure and implicates clear benefits for the metabolic control and quality of life of patients otherwise suffering from pancreoprivic diabetes mellitus. The positive effects of stem cell transplantation on the regeneration capacity of the liver is now preclinically well described and is currently under evaluation in clinical studies. Besides paracrine effects, the shedding of microparticles, which influence cell-cell communication by horizontal transfer of microRNA appears to be responsible for the immunomodulatory and pro-regenerative effects; however, it is still not completely understood how these cells interact with regenerating liver tissue. Tissue engineering techniques may have a profound impact on future oncological surgery but are so far limited to individual therapy attempts and preclinical experiments.

Conclusion

The possibility of an autologous islet transplantation should be evaluated before pancreatic resection for certain indications (e.?g. chronic pancreatitis, pancreatic trauma and complications after resection). Recent single center data demonstrate that this procedure can be safely and efficiently performed even for neoplastic pancreatic diseases. Due to encouraging preclinical results, the impact of stem cell transplantation for patients suffering from liver disease or for cancer patients before or during extended liver resection is currently under evaluation in clinical studies.

     

Clinical Characteristics and Survival of European Patients with Resectable Large Hepatocellular Carcinomas

Purpose

Large hepatocellular carcinoma (HCC) presents on cirrhosis or in the absence of cirrhosis. Prognostic factors include both tumor and liver factors. Evaluate clinical and tumor characteristics of a group of large resected HCC in European patients.

Methods

Data for patients with HCC >7 cm who underwent liver resection between 1992 and 2011 were analyzed. Patients were dichotomized into those with tumor diameters of 7–10 cm or >10 cm and their characteristics and outcomes were compared.

Results

A total of 65 hepatectomies for HCC ≥7 cm were performed. Severe fibrosis or cirrhosis was present in 41.5 % of patients. Thirty-seven (56.9 %) patients had HCC ≥10 cm. Mortality and morbidity rates were 1.5 % and 37.5 %, respectively. Preoperative blood platelet levels and serum alkaline phosphatase (ALKP) levels showed significant differences between the groups. The 3-year survival was 43.5 % and 17.4 % for patients with tumors 7–10 and ≥10 cm, respectively.

Conclusions

Patients with large size HCC and preserved liver function can be resected with low operative risk. ALKP levels and platelet counts were higher in the larger tumors. Given these patterns of clinical and biochemical characteristics, this group of tumors may be a selected subset of large HCCs and might potentially benefit from surgical resection.     

C-reactive protein in liver cancer surgery

Aims

The aim of this article is to review the current state of knowledge with regard to the importance of C-reactive protein (CRP) in patients undergoing hepatic resection for malignancy both in terms of its role as an acute phase reactant and predictor of outcome.

Methods

An electronic search was performed of the medical literature using the MEDLINE database to identify relevant articles that included the search terms: C-reactive protein; CRP; hepatocellular carcinoma; colorectal liver metastases; hepatic resection; and liver resection.

Results

The limited published data in relation to CRP and liver resection is contradictory. There are studies correlating an acute phase reactant-type postoperative rise in CRP with both good and poor outcome following colorectal liver metastases resection. In relation to prognosis, the only available publication indicates that a high preoperative CRP is a poor prognostic indicator in relation to patient survival. Data for CRP and resection of HCC is equally as limited with early evidence suggesting a correlation between CRP and stage of disease, and documenting an acute temporary elevation in CRP following resection.

Conclusions

The importance of CRP as a marker of both early postoperative outcome and long-term prognosis in patients with hepatic malignancies is at present unclear. Further studies are required to clarify the changes and more accurately define the mechanism by which CRP is being up-regulated.     

Role of hepatic trisectionectomy in advanced hepatocellular carcinoma

Background

Advanced hepatocellular carcinoma (HCC) with underlying cirrhosis poses a major operative challenge. Patients have a dismal prognosis without curative resection. The role of hepatic trisectionectomy in these patients is not established. The aim of this study was to analyze and compare the perioperative outcome and prognosis of patients undergoing trisectionectomy with hepatic resection of a lesser extent.

Laparoscopic wedge resection of the stomach for gastrointestinal stromal tumor (GIST): non-touch lesion lifting method

Background

Laparoscopic surgery for GIST carries a risk of intraoperative tumor dissemination. To avoid tumor dissemination, we have utilized a “non-touch” method for surgical resection of GIST since 2000.

Methods

Forty-two patients with gastric GIST were treated at our institution between 2000 and 2012. Laparoscopic wedge resection of the stomach was used as the standard procedure for tumors that were 2–5 cm in size. Tumors larger than 5 cm were treated with open surgery. Our non-touch procedure included a lesion-lifting method using traction sutures at the normal stomach wall around the tumor. Intraoperative gastroscopy was utilized to confirm the location of the tumor with laparoscopy. After lifting of the tumor, tumors with a clear operative margin were resected using a linear stapler. Tumors located at the posterior wall of the stomach or located near the esophagogastric junction were resected using traction sutures.

Results

Median operative time was 140 min and median blood loss was 0 ml. Postoperative course was uneventful excepting one patient who experienced postoperative bleeding. The median postoperative stay was 7 days. One patient developed liver metastasis after surgery. None of the patients had local recurrence or peritoneal recurrence case.

Conclusion

This non-touch lesion-lifting method was useful for the surgical management of gastric GIST.     

Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma

Purpose

We have previously reported that 24-h intra-arterial combination chemotherapy (IACC) prolongs the survival of patients with advanced hepatocellular carcinoma (aHCC). However, it has also been reported that 5-fluorouracil (5-FU) exacerbates liver damage in patients with liver cirrhosis (LC). The aim of this study was to clarify the hepatotoxicity of IACC in LC patients with aHCC.

Methods

Twenty-one adult Japanese patients (20 men and 1 woman) with aHCC and LC underwent IACC between 2004 and 2007 at our hospital. These patients showed multiple partial responses or stable disease, except for five patients who showed no response and three patients with tumors more than 30 mm in diameter. All patients had inoperable disease on the basis of computed tomography (CT) findings. IACC (leucovorin at 12 mg/h, cisplatin at 10 mg/h, and 5-FU at 250 mg/22 h) was delivered via the proper hepatic artery every 5 days for 4 weeks.

Results

Twelve patients were in Child-Pugh class A (group A), and nine were in class B (group B). The Child-Pugh score was significantly increased after chemotherapy compared with before chemotherapy in both groups. Serum albumin was significantly decreased after chemotherapy, and the number of patients with ascites also increased after chemotherapy. Serum type IV collagen and N-terminal propeptide of type III procollagen were significantly increased after chemotherapy, although there was no significant change in serum aminotransferases.

Conclusions

IACC might cause hepatotoxicity that induces fibrosis without releasing aminotransferases.