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1.  Mirizzi syndrome type IV associated with cholecystocolic fistula: a very rare condition- report of a case 
BMC Surgery  2007;7:6.
Mirizzi syndrome is a rare complication of prolonged cholelithiasis with presence of large, impacted gallstone into the Hartman's pouch, causing chronic extrinsic compression of common bile duct (CBD). Fistula formation between the CBD and the gallbladder may represent an outcome of that condition. According to Mirizzi's classification and Csendes's subclassification, Mirizzi syndrome type IV represents the most uncommon type (4%).
Spontaneous biliary-enteric fistulas have also been rarely reported (1.2–5%) in a large series of cholecystectomies. Cholecystocolic fistula is the most infrequent biliary enteric fistula, causing significant morbidity and representing a diagnostic challenge.
Case presentation
We describe a very rare, to our knowledge, combination of Mirizzi syndrome type IV and cholecystocolic fistula. A 52 year old male, presented to our clinic complaining of episodic diarrhea (monthly episodes lasting 16 days), high temperature (38°C–39°C), right upper quadrant pain without jaundice. The definitive diagnosis was made intraoperatively. Magnetic Resonance Imaging (MRI) and Endoscopic Retrograde Cholangiopancreatography (ERCP) demonstrated the presence of Mirizzi syndrome with cholecystocolic fistula formation. The patient was operated upon, and cholecystectomy, cholecystocolic fistula excision and Roux-en-Y biliary-enteric anastomosis were undertaken with excellent post-operative course.
Appropriate biliary tree imaging with ERCP and MRI/MRCP is essential for the diagnosis of Mirizzi syndrome and its complications. Cholecystectomy, fistula excision and biliary-enteric anastomosis with Roux-en-Y loop appears to be the most appropriate surgical intervention in order to avoid damage to Calot's triangle anatomic elements. Particularly in our case, ERCP was a valuable diagnostic tool that Mirizzi syndrome type IV and cholecystocolic fistula.
PMCID: PMC1892769  PMID: 17531103
2.  A case of biliary gastric fistula following percutaneous radiofrequency thermal ablation of hepatocellular carcinoma 
Percutaneous radiofrequency thermal ablation (RFA) is an effective and safe therapeutic modality in the management of liver malignancies, performed with ultrasound guidance. Potential complications of RFA include liver abscess, ascites, pleural effusion, skin burn, hypoxemia, pneumothorax, subcapsular hematoma, hemoperitoneum, liver failure, tumour seeding, biliary lesions. Here we describe for the first time a case of biliary gastric fistula occurred in a 66-year old man with a Child’s class A alcoholic liver cirrhosis as a complication of RFA of a large hepatocellular carcinoma lesion in the III segment. In the light of this case, RFA with injection of saline between the liver and adjacent gastrointestinal tract, as well as laparoscopic RFA, ethanol injection (PEI), or other techniques such as chemoembolization, appear to be more indicated than percutaneous RFA for large lesions close to the gastrointestinal tract.
PMCID: PMC4066018  PMID: 17278208
Radiofrequency thermal ablation; Hepatocellular carcinoma; Biliary gastric fistula; Complications
3.  Survival after Locoregional Treatments for Hepatocellular Carcinoma: A Cohort Study in Real-World Patients 
The Scientific World Journal  2012;2012:564706.
Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79–1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64–1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66–1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment.
PMCID: PMC3356712  PMID: 22654628
4.  Effect of branched-chain amino acids in patients receiving intervention for hepatocellular carcinoma 
AIM: To investigate the usefulness of branched-chain amino acids (BCAA) before transarterial chemoembolization (TACE) or radiofrequency ablation (RFA).
METHODS: We investigated the usefulness of pre-intervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment. A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study. Mean changes from baseline (Δ) in serum albumin (Alb), C-reactive protein (CRP), and transaminase levels, as well as peak body temperature were also determined and compared at days 2, 5, and 10 after the start of TACE or RFA.
RESULTS: In patients who underwent TACE or RFA, BCAA pre-intervention significantly suppressed the development of post- intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course. After TACE, the ΔAlb peaked on day 2, remained constantly lower in BCAA-treated patients, compared to the control group, and was -0.13 ± 0.42 g/dL in BCAA-treated patients and -0.33 ± 0.51 g/dL in untreated patients on day 10. The ΔCRP was also significantly lower in BCAA-treated patients on days 2, 5 and 10 after TACE. Like the trends noted after TACE, a similar tendency was noted as to the ΔAlb and ΔCRP after RFA. The changes in serum Alb level were inversely correlated with CRP changes; therefore, a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.
CONCLUSION: Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate post-operative complications in patients undergoing TACE or RFA.
PMCID: PMC3949276  PMID: 24627603
Branched-chain amino acids; Cirrhosis; Hepatocellular carcinoma; Transarterial chemoembolization; Radiofrequency ablation; Hypoalbuminemia
5.  Radiofrequency ablation following first-line transarterial chemoembolization for patients with unresectable hepatocellular carcinoma beyond the Milan criteria 
BMC Gastroenterology  2014;14:11.
Recent studies suggest that a combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have theoretical advantages over TACE alone for treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the effectiveness and safety of radiofrequency ablation following first-line TACE treatment in the management of HCC beyond the Milan Criteria.
Forty-five patients who consecutively underwent RFA following first-line TACE treatment for HCC beyond the Milan criteria were enrolled in this study. RFA was performed within 1–2 months after TACE treatment in patients who had incomplete necrotic tumor nodules. Primary effectiveness, complications, survival rates, and prognostic factors were evaluated retrospectively.
Complete ablation was achieved in 76.2% of the lesions according to 1-month follow-up computed tomography/magnetic resonance imaging evaluation. The mean follow-up period was 30.9 months (range 3–94 months). There were no major complications after RFA therapy. The median overall survival was 29 months (range 20–38 months), with 1-, 2-, and 3-year survival of 89%, 61%, and 43%, respectively. Multivariate analysis revealed that tumor diameter (P = 0.045, hazard ratio [HR] = 0.228, 95% confidence interval [CI]: 0.054-0.968) and pretreatment serum alpha-fetoprotein level (P = 0.024, HR = 2.239, 95% CI: 1.114-4.500) were independent predictors for long-term survival.
HCC beyond the Milan criteria can be completely and safely ablated by radiofrequency ablation following first-line TACE treatment with a low rate of complications and favorable survival outcome. Further assessment of the survival benefits of combination treatment for HCCs beyond the Milan Criteria is warranted.
PMCID: PMC3890612  PMID: 24410841
Hepatocellular carcinoma; Radiofrequency ablation; Transcatheter arterial chemoembolization; Milan criteria
6.  Transarterial embolisation of hepatocellular carcinoma with doxorubicin-eluting beads: single centre early experience 
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.
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.
DEB TACE is safe and effective in select group of patients. Survival may be improved when combined with other treatment modality.
PMCID: PMC3097792  PMID: 21611067
Drug-eluting beads; doxorubicin; embolisation; hepatocellular carcinoma
7.  Radio Frequency Ablation for Primary Liver Cancer 
Executive Summary
The Medical Advisory Secretariat undertook a review of the evidence on the safety, clinical effectiveness, and cost-effectiveness of radio frequency ablation (RFA) compared with other treatments for unresectable hepatocellular carcinoma (HCC) in Ontario.
Liver cancer is the fifth most common type of cancer globally, although it is most prevalent in Asia and Africa. The incidence of liver cancer has been increasing in the Western world, primarily because of an increased prevalence of hepatitis B and C. Data from Cancer Care Ontario from 1998 to 2002 suggest that the age-adjusted incidence of liver cancer in men rose slightly from 4.5 cases to 5.4 cases per 100,000 men. For women, the rates declined slightly, from 1.8 cases to 1.4 cases per 100,000 women during the same period. Most people who present with symptoms of liver cancer have a progressive form of the disease. The rates of survival in untreated patients in the early stage of the disease range from 50% to 82% at 1 year and 26% to 32% at 2 years. Patients with more advanced stages have survival rates ranging from 0% to 36% at 3 years. Surgical resection and transplantation are the procedures that have the best prognoses; however, only 15% to 20% of patients presenting with liver cancer are eligible for surgery. Resection is associated with a 50% survival rate at 5 years.
The Technology: Radio Frequency Ablation
RFA is a relatively new technique for the treatment of small liver cancers that cannot be treated with surgery. This technique applies alternating high-frequency electrical currents to the cancerous tissue. The intense heat leads to thermal coagulation that can kill the tumour. RFA is done under general or local anesthesia and can be done percutaneously (through the skin with a small needle), laparoscopically (microinvasively, using a small video camera), or intraoperatively. Percutaneous RFA is usually a day procedure.
The leading international organizations for health technology assessments, including the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) and the International Network of Agencies for Health Technology Assessment (INAHTA), were scanned for previous systematic reviews on RFA. The Cochrane Library Database was also scanned. The most recent systematic review examined the literature up to October 2003. Five previous health technology assessments were found.
To update the international systematic reviews, the Medical Advisory Secretariat systematically reviewed the literature from January 1, 2003 to the third week of April 2004. Peer-reviewed literature from EMBASE, MEDLINE (including in-process and other nonindexed citations) and the Cochrane Library Database were searched for the following search terms:
Catheter ablation
Radiofrequency or radio-frequency or radio frequency or RFA or RFTA
Liver neoplasms or liver cancer or hepatocellular or hepatocellular or hepatic
The inclusion criteria were as follows:
Population: patients with primary hepatocellular carcinoma
Procedure: RFA used as the only treatment (not as an adjunct)
Language: publication in English
Published health technology assessments, guidelines, and peer-reviewed literature (abstracts and in-progress manuscripts)
Outcomes: therapeutic response (% complete ablation), mortality, survival, and tumour recurrence
Grey literature, where relevant, was also reviewed.
Summary of Findings
The Medical Advisory Secretariat included 5 previous health technology assessments from 2002 to 2004 and 9 peer-reviewed studies from January 2003 to April 2004 in its review. The health technology assessments suggested that RFA is as safe and effective for treating up to 3 or 4 small (< 4 to 5 cm), unresectable liver tumours in the short term (2 years). One small randomized controlled trial (RCT) that compared RFA with percutaneous ethanol injection (PEI), another ablative technique, suggested that RFA is at least as safe and effective for small unresectable primary liver tumours compared to PEI. However, the patient populations and comparison technologies in the peer-reviewed literature and the previous health technology assessments were heterogeneous; therefore, meta-analyses could not be performed.
RFA has also been used to treat colorectal and neuroendocrine liver metastases and kidney, lung, breast, and bone cancer. Although this report did not focus on these indications because of a paucity of published evidence of effectiveness, some individual patients with the above indications may benefit from RFA; therefore, RFA may quickly diffuse into these areas. Various clinical trials focussing on these indications are underway.
Level 2 evidence suggests RFA is as safe and perhaps more effective than percutaneous ethanol injection to treat HCC.
RFA and percutaneous ethanol injection are more effective and more cost-effective than transcatheter arterial chemoembolization.
RFA is marginally more expensive, yet more cost-effective than percutaneous ethanol injection.
Complications are few, but experienced interventional radiologists should do RFA.
RFA may benefit some patients with liver metastases or other primary cancers, although published evidence of effectiveness has not yet been established.
PMCID: PMC3387776  PMID: 23074458
8.  Radiofrequency ablation (RFA) of renal cell carcinoma (RCC): experience in 200 tumours 
Bju International  2013;113(3):416-428.
To evaluate our clinical experience with percutaneous image-guided radiofrequency ablation (RFA) of 200 renal tumours in a large tertiary referral university institution.
Patients and Methods
Image-guided RFA (ultrasonography or computed tomography [CT]) of 200 renal tumours in 165 patients from June 2004 to 2012 was prospectively evaluated. Institutional Review Board approval was granted.
The treatment response and technical success were defined by absence of contrast enhancement within the tumour on contrast enhanced CT or magnetic resonance imaging.
Both major and minor complications, glomerular filtration rate (GFR) before and after RFA, the management and outcomes of the complications, as well as oncological outcome were prospectively documented.
Multivariate analysis was used to determine variables associated with major complications and also the percentage GFR change after RFA.
The overall (OS), 5-year cancer-specific (CSS), local recurrence-free (LRFS) and metastasis-free survival (MFS) rates are presented using the Kaplan–Meier curves.
In all, 200 tumours were RF ablated with a mean (range) tumour size of 2.9 (1–5.6) cm and the mean (range) patient age was 67.7 (21–88.6) years with a mean follow-up period of 46.1 months.
The primary technical and overall technical success rate was 95.5% and 98.5%, respectively. Two independent predictors of successful RFA in a single sitting were tumour size (<3 cm) and exophytic location in multivariate logistic regression analysis.
Major complications included ureteric injury (six patients), calyceal-cutaneous fistula (one), acute tubular necrosis (one) and abscess (two). Two independent predictors of ureteric injury were central location and lower pole position.
Within this cohort of patients, only four patients developed significant renal function deterioration i.e. >25% decreased in GFR. In all, 161 (98%) patients of the 165 patients have preservation of renal function. Any change in renal function after RFA was not influenced by tumour factors or solitary kidney status.
In our clinical series, this yielded a 5-year OS, CSS, LRFS and MFS rates of 75.8%, 97.9%, 93.5% and 87.7% respectively.
Image-guided RFA is a safe, nephron sparing and effective treatment for small renal cell carcinoma (RCC) tumours with a low rate of recurrence and has good 5-year CSS and MFS rates.
PMCID: PMC4233988  PMID: 24053769
radiofrequency ablation; renal cell carcinoma; complication; survival rates
9.  Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma 
AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC).
METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, recurrence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P < 0.05 and I2 > 50%, the assumption of homogeneity was deemed invalid, and the random-effects model was used; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted using Review manager (version 4.2.2.) from the Cochrane collaboration.
RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a significantly higher overall survival rate (OR1-year = 2.96, 95%CI: 1.84-7.74, P < 0.001; OR2-year = 3.72, 95%CI: 1.24-11.16, P = 0.02; OR3-year = 2.65, 95%CI: 1.81-3.86, P < 0.001) and recurrence-free survival rate (OR3-year = 3.00, 95%CI: 1.75-5.13, P < 0.001; OR5-year = 2.26, 95%CI: 1.43-3.57, P = 0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR = 0.60, 95%CI: 0.42-0.88, P = 0.008) and there was no significant difference on major complications between two different kinds of treatment (OR = 1.20, 95%CI: 0.31-4.62, P = 0.79). Additionally, the meta-analysis data of subgroups revealed that the survival rate was significantly higher in patients with intermediate- and large-size HCC underwent RFA plus TACE than in those underwent RFA monotherapy; however, there was no significant difference between RFA plus TACE and RFA on survival rate for small HCC.
CONCLUSION: The combination of RFA with TACE has advantages in improving overall survival rate, and provides better prognosis for patients with intermediate- and large-size HCC.
PMCID: PMC3699038  PMID: 23840128
Radiofrequency ablation; Transcatheter arterial chemoembolization; Hepatocellular carcinoma; Meta-analysis
10.  Role of Radiofrequency Ablation in Patients with Hepatocellular Carcinoma Who Undergo Prior Transarterial Chemoembolization: Long-Term Outcomes and Predictive Factors 
Gut and Liver  2014;8(5):543-551.
The role of radiofrequency ablation (RFA) remains uncertain in patients with viable hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).
A total of 101 patients (April 2007 to August 2010) underwent RFA for residual or recurrent HCC after TACE. We analyzed their long-term outcomes and predictive factors.
The overall survival rates after RFA were 93.1%, 65.4%, and 61.0% at 1, 3, and 5 years, respectively. Predictive factors for favorable overall survival were Child-Pugh class A (hazard ratio [HR], 3.45; p=0.001), serum α-fetoprotein (AFP) level <20 ng/mL (HR, 2.90; p=0.02), and recurrent tumors after the last TACE (HR, 3.14; p=0.007). The cumulative recurrence-free survival rate after RFA at 6 months was 50.1%. Predictive factors for early recurrence (within 6 months) were serum AFP level 20 ng/mL (HR, 3.02; p<0.001), tumor size 30 mm at RFA (HR, 2.90; p=0.005), and nonresponse to the last TACE (HR, 2.13; p=0.013).
Patients with recurrent or residual HCC who undergo prior TACE show a favorable overall survival, although their tumors seem to recur early and frequently. While good liver function, a low serum AFP level, and recurrent tumors were independent predictive factors for a favorable overall survival, poor response to TACE, a high serum AFP level, and large tumors are associated with early recurrence.
PMCID: PMC4164247  PMID: 25071073
Carcinoma; hepatocellular; Transarterial chemoembolization; Radiofrequency ablation; Outcome; Recurrence
11.  Cholecystocolic Fistula: A Diagnostic Enigma 
Cholecystocolic fistula is a rare biliary-enteric fistula with a variable clinical presentation. Despite modern diagnostic tools, a high degree of suspicion is required to diagnose it preoperatively. Biliary-enteric fistulae have been found in 0.9% of patients undergoing biliary tract surgery. The most common site of communication of the fistula is a cholecystoduodenal (70%), followed by cholecystocolic (10–20%), and the least common is the cholecystogastric fistula accounting for the remainder of cases. These fistulae are treated by open as well as laparoscopic surgery, with no difference in intraoperative and postoperative complications.
We report here a case of obstructive jaundice, which was investigated with a plain film of the abdomen, abdominal ultrasonography, and endoscopic retrograde cholangiopancreatography, but none of these gave us any clue to the presence of the fistula was discovered incidentally during an open surgery and was appropriately treated.
PMCID: PMC2702960  PMID: 19568555
Biliary-enteric fistula; cholecystectomy; cholecystocolic fistula ERCP
12.  Post-treatment imaging of liver tumours 
Cancer Imaging  2007;7(Special issue A):S28-S36.
In the past few years, great improvements have been made to achieve local tumour control of primary liver malignancies and liver metastases. For hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE) and tumour ablation techniques, including percutaneous ethanol injection (PEI), radiofrequency ablation (RF), and laser-induced interstitial thermotherapy (LITT) have been developed. For colorectal liver metastases, surgery is still the standard technique in localised disease, although percutaneous RF ablation has gained considerable acceptance. In patients with widespread disease, chemotherapy with new drugs offers improved survival. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice to evaluate treatment response. The present review demonstrates imaging findings of complete and incomplete tumour control after intervention as well as the imaging spectrum of complications. Imaging guidelines according to the World Health Organization and Response Evaluation Criteria In Solid Tumors (RECIST) for assessment of chemotherapy response are presented.
PMCID: PMC2727978  PMID: 17921098
Liver; Metastasis; hepatocellular carcinoma (HCC); magnetic resonance imaging (MRI); computed tomography (CT)
13.  Role of surgical resection for multiple hepatocellular carcinomas 
AIM: To clarify the role of surgical resection for multiple hepatocellular carcinomas (HCCs) compared to transarterial chemoembolization (TACE) and liver transplantation (LT).
METHODS: Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008, 160 patients who met the following criteria were retrospectively enrolled: (1) two or three radiologically diagnosed HCCs; (2) no radiologic vascular invasion; (3) Child-Pugh class A; (4) main tumor smaller than 5 cm in diameter; and (5) platelet count greater than 50 000/mm3. Long-term outcomes were compared among the following three treatment modalities: surgical resection or combined radiofrequency ablation (RFA) (n = 36), TACE (n = 107), and LT (n = 17). The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test. To identify the patients who gained a survival benefit from surgical resection, we also investigated prognostic factors for survival following surgical resection. Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model.
RESULTS: The overall survival (OS) rate was significantly higher in the surgical resection group than in the TACE group (48.1% vs 28.9% at 5 years, P < 0.005). LT had the best OS rate, which was better than that of the surgical resection group, although the difference was not statistically significant (80.2% vs 48.1% at 5 years, P = 0.447). The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group (88.2% vs 11.2% at 5 years, P < 0.001). Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6% (20/36) in the resection group and 93.5% (100/107) in the TACE group. There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients, multi-site resection was performed in 5 patients, and combined resection with RFA was performed in 8 patients. In the TACE group, only 34 patients (31.8%) were recorded as having complete remission after primary TACE. Seventy-two patients (67.3%) were retreated with repeated TACE combined with other therapies. In patients who underwent surgical resection, the 16 patients who did not have cirrhosis had higher 5-year OS and disease-free survival rates than the 20 patients who had cirrhosis (80.8% vs 25.5% 5-year OS rate, P = 0.006; 22.2% vs 0% 5-year disease-free survival rate, P = 0.048). Surgical resection in the 20 patients who had cirrhosis did not provide any survival benefit when compared with TACE (25.5% vs 24.7% 5-year OS rate, P = 0.225). Twenty-nine of the 36 patients who underwent surgical resection experienced recurrence. Of the patients with cirrhosis, 80% (16/20) were within the Milan criteria at the time of recurrence after resection.
CONCLUSION: Among patients with two or three HCCs, no radiologic vascular invasion, and tumor diameters ≤ 5 cm, surgical resection is recommended only in those without cirrhosis.
PMCID: PMC3554821  PMID: 23372359
Hepatocellular carcinoma; Hepatectomy; Liver transplantation; Chemoembolization; Cirrhosis
14.  The role of interventional radiology in the management of hepatocellular carcinoma 
Current Oncology  2014;21(3):e480-e492.
Hepatocellular carcinoma (hcc) is one of the most common causes of cancer-related death worldwide. Overall, liver transplantation and resection are the only available treatments with potential for cure. Various locoregional therapies are widely used to manage patients with advanced hcc or as a bridging therapy for patients with early and intermediate disease. This article reviews and evaluates the role of interventional radiology in the management of such cases by assessing various aspects of each method, such as effect on rates of survival, recurrence, tumour response, and complications.
A systemic search of PubMed, medline, Ovid Medline In-Process, and the Cochrane Database of Systematic Reviews retrieved all related scientific papers for review.
Needle core biopsy is a highly sensitive, specific, and accurate method for hcc grading. Portal-vein embolization provides adequate expansion of the future liver remnant, making more patients eligible for resection. In focal or multifocal unresectable early-stage disease, radiofrequency ablation tops all other thermoablative methods. However, microwave ablation is preferred in large tumours and in patients with Child–Pugh B disease. Cryoablation is preferred in recurrent disease and in patients who are poor candidates for anesthesia. Of the various transarterial modalities—transarterial chemoembolization (tace), drug-eluting beads, and transarterial radio-embolization (tare)—tace is the method of choice in Child–Pugh A disease, and tare is the method of choice in hcc cases with portal vein thrombosis.
The existing data support the importance of a multidisciplinary approach in hcc management. Large randomized controlled studies are needed to provide clear indication guidelines for each method.
PMCID: PMC4059812  PMID: 24940108
Interventional radiology; hepatocellular carcinoma; liver biopsy; ablation; embolization; drug-eluting beads
15.  Combination of percutaneous radiofrequency ablation with transarterial chemoembolization for hepatocellular carcinoma: observation of clinical effects 
To observe the clinical effect of radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).
A total of 92 cases of advanced primary liver cancer underwent TACE and RFA treatment from June 2005 to 2011 at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College. A total of 88 cases with complete clinical treatment and follow-up data were divided into two groups: 43 patients treated with TACE (TACE group) and 45 patients that received TACE combined with RFA treatment (TACE + RFA group). After clinical data assessment, tumor size and survival status were not significantly different between the groups as determined by stratified analysis.
Before and after surgery, spiral CT radiography and color comparison observed ablation conditions. The tumor necrosis rates after treatment (CR + PR) were 67.4% (29/43) and 91.1% (41/45) for the TACE and combined treatment groups, respectively, and the difference was statistically significant (P<0.05). The quality of life was significantly improved for patients undergoing TACE + RFA compared with the control group. Survival duration was not significantly different in patients undergoing TACE + RFA compared with the control group.
In this study, the effect of RFA combined with TACE treatment was better than TACE alone in treating advanced HCC.
PMCID: PMC4153924  PMID: 25232222
Liver cancer; radiofrequency ablation (RFA); transcatheter arterial chemoembolization (TACE); quality of life; survival period
16.  Extrahepatic biliary obstruction after percutaneous tumour ablation for hepatocellular carcinoma: aetiology and successful treatment with endoscopic papillary balloon dilatation 
Gut  2005;54(5):698-702.
Background and aims: Percutaneous tumour ablation (PTA), such as ethanol injection and radiofrequency ablation, is now recognised as a primary treatment for hepatocellular carcinoma (HCC). Although PTA is a relatively safe procedure, it can cause biliary obstruction as a rare complication. As patients with cirrhosis undergoing surgery or endoscopic retrograde cholangiopancreatography/sphincterotomy have a high mortality rate from bleeding, we adopted the use of endoscopic papillary balloon dilatation (EPBD) in these patients and now report the results. We retrospectively analysed the incidence of biliary obstruction after PTA and the efficacy of treatment with EPBD.
Patients and methods: A total of 1043 patients with HCC were treated by PTA, of whom 538 were treated with transarterial embolisation with up to eight years of follow up.
Results: There were 17 (1.6%) cases of hilar obstruction due to tumour progression and 35 (3.4%) cases of extrahepatic obstruction. Apart from the expected causes of biliary obstruction (haemobilia n = 11, gallstones n = 11, and three miscellaneous causes), we found that 10 patients had obstruction due to biliary casts. This is the first description of biliary casts after percutaneous tumour ablation therapy. Extrahepatic biliary obstruction by procedure related haemobilia occurred within three days of PTA while other causes occurred between 0 and 17 (average 4.9) months. Biliary casts occurred more frequently after ethanol injection than after radiofrequency ablation. EPBD successfully dissipated biliary obstruction in 33 of 35 cases, while two died due to hepatic failure despite successful drainage.
Conclusions: Extrahepatic biliary obstruction is an uncommon complication after PTA for HCC, and can be safely and effectively treated with EPBD, despite impaired liver function.
PMCID: PMC1774480  PMID: 15831919
biliary cast; haemobilia; choledocholithiasis; endoscopic papillary balloon dilatation; percutaneous ethanol injection therapy
17.  Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma 
AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care.
METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, α-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses.
RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%, and 43%) compared to PEI treatment alone (2) (1-, 3-, 5-year survival: 65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%) while PEI after stratification to best supportive care (4) was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n < 5), tumor size (< 5 cm), no ascites before PEI, and stable serum cholinesterase after PEI (P < 0.05). The mortality within 2 wk after PEI was 2.8% (n = 3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All complications could be managed non-surgically.
CONCLUSION: Repeated single-session PEI is effective in patients with advanced HCC at an acceptable and manageable complication rate. Patients stratified to a combination of TACE and PEI can expect longer survival than those stratified to repeated PEI alone. Furthermore, patients with large or multiple tumors in good clinical status may also profit from a combination of TACE and reconsideration for secondary PEI.
PMCID: PMC4087463  PMID: 16773687
HCC; Single-session PEI; TACE; Survival; Prediction
18.  Percutaneous Management of a Bronchobiliary Fistula after Radiofrequency Ablation in a Patient with Hepatocellular Carcinoma 
Korean Journal of Radiology  2009;10(4):411-415.
Radiofrequency ablation (RFA) is a minimally invasive, image-guided procedure for the treatment of hepatic tumors. While RFA is associated with relatively low morbidity, sporadic bronchobiliary fistulae due to thermal damage may occur after RFA, although the incidence is rare. We describe a patient with a bronchobiliary fistula complicated by a liver abscess that occurred after RFA. This fistula was obliterated after placement of an external drainage catheter into the liver abscess for eight weeks.
PMCID: PMC2702053  PMID: 19568472
Bronchobiliary fistula; Radiofrequency ablation; Hepatocellular carcinoma; Liver abscess; Percutaneous drainage
19.  Successful Interventional Treatment for Arterioportal Fistula Caused by Radiofrequency Ablation for Hepatocellular Carcinoma 
Case Reports in Oncology  2014;7(3):833-839.
Radiofrequency ablation (RFA) is commonly used as a treatment for small hepatocellular carcinoma (HCC). Although several complications such as intraperitoneal bleeding are often observed after RFA, hepatic arterioportal fistula (APF) is a less frequently occurring complication. In this study, we describe two cases of APF caused by RFA, which was successfully occluded by an interventional approach. Case 1 involved a 68-year-old man with solitary HCC in segment VIII of the liver. Both contrast-enhanced computed tomography and color Doppler sonography indicated an APF between the anterosuperior branch of the right hepatic artery (A8) and the portal branch (P8). Concordant with these findings, digital subtraction angiography (DSA) revealed an APF in segment VIII of the liver. Subsequently, the APF was successfully occluded by transarterial embolization (TAE) using gelatin sponge particles. Case 2 involved a 67-year-old man with solitary HCC in segment VII of the liver. Although he developed obstructive jaundice because of hemobilia after RFA, it was improved by endoscopic nasobiliary drainage and the systemic administration of antibiotics. In addition, color Doppler sonography revealed a disturbed flow of the right branch of the portal vein. Similar to case 1, DSA showed an APF between A8 and P8. The APF was successfully embolized by TAE using microcoils. In conclusion, it appears that the formation of APF should be checked after RFA. It is preferable to treat RFA-induced APF promptly by an interventional approach to avoid secondary complications such as portal hypertension and liver dysfunction.
PMCID: PMC4307006
Hepatocellular carcinoma; Radiofrequency ablation; Arterioportal fistula; Transarterial embolization
20.  Radiofrequency ablation or microwave ablation combined with transcatheter arterial chemoembolization in treatment of hepatocellular carcinoma by comparing with radiofrequency ablation alone 
To compare radiofrequency ablation (RFA) or microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) with RFA or MWA monotherapy in hepatocellular carcinoma (HCC).
A prospective, randomized, controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Southeast University. The patients were randomly assigned into the TACE-RFA or TACE-MWA (combined treatment group) and the RFA-alone or MWA-alone groups (control group). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects.
Until the time of censor, 17 patients in the TACE-RFA or TACE-MWA group had died. The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months (range, 29 to 62 months). The 1-, 3- and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6%, 68.1% and 61.7%, respectively. Twenty-five patients in the RFA or MWA group had died. The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months (range, 28 to 62 months). The 1-, 3- and 5-year overall survival for the RFA or MWA group was 85.1%, 59.6% and 44.7%, respectively. The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio (HR), 0.526; 95% confidence interval (95% CI), 0.334-0.823; P=0.002], and showed better recurrence-free survival than the RFA or MWA group (HR, 0.582; 95% CI, 0.368-0.895; P=0.008).
RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.
PMCID: PMC3937757  PMID: 24653633
Radiofrequency ablation (RFA); transcatheter arterial chemoembolization (TACE); hepatocellular carcinoma (HCC)
21.  Temporary Placement of Stent Grafts in Postsurgical Benign Biliary Strictures: a Single Center Experience 
Korean Journal of Radiology  2011;12(6):708-713.
To evaluate the effect of temporary stent graft placement in the treatment of benign anastomotic biliary strictures.
Materials and Methods
Nine patients, five women and four men, 22-64 years old (mean, 47.5 years), with chronic benign biliary anastomotic strictures, refractory to repeated balloon dilations, were treated by prolonged, temporary placement of stent-grafts. Four patients had strictures following a liver transplantation; three of them in bilio-enteric anastomoses and one in a choledocho-choledochostomy. Four of the other five patients had strictures at bilio-enteric anastomoses, which developed after complications following laparoscopic cholecystectomies and in one after a Whipple procedure for duodenal carcinoma. In eight patients, balloon-expandable stent-grafts were placed and one patient was treated by insertion of a self-expanding stent-graft.
In the transplant group, treatment of patients with bilio-enteric anastomoses was unsuccessful (mean stent duration, 30 days). The patient treated for stenosis in the choledocho-choledochostomy responded well to consecutive self-expanding stent-graft placement (total placement duration, 112 days). All patients with bilio-enteric anastomoses in the non-transplant group were treated successfully with stent-grafts (mean placement duration, 37 days).
Treatment of benign biliary strictures with temporary placement of stent-grafts has a positive effect, but is less successful in patients with strictures developed following a liver transplant.
PMCID: PMC3194775  PMID: 22043153
Biliary anastomotic stricture; Benign stricture; Liver transplant
22.  Bilio-entero-gastrostomy: prospective assessment of a modified biliary reconstruction with facilitated future endoscopic access 
BMC Surgery  2012;12:9.
Hepaticojejunostomy (HJ) is the classical reconstruction for benign biliary stricture. Endoscopic management of anastomotic complications after hepaticojejunostomy is extremely difficult. In this work we assess a modified biliary reconstruction in the form of bilio-entero-gastrostomy (BEG) regarding the feasibility of endoscopic access to HJ and management of its stenosis if encountered.
From October 2008 till February 2011 all patients presented to the authors with benign biliary stricture who needed bilio-enteric shunt were considered. For each patient bilio-entero-gastrostomy (BEG) of either type I, II or III was constructed. In the fourth week postoperatively, endoscopy was performed to explore the possibility to access the biliary anastomosis and perform cholangiography.
BEG shunt was performed for seventeen patients, one of whom, with BEG type I, died due to myocardial infarction leaving sixteen patients with a diagnosis of postcholecystectomy biliary injury (9), inflammatory stricture with or without choledocholithiasis (5) and strictured biliary shunt (2). BEG shunts were either type I (3), type II (3) or type III (10). Endoscopic follow up revealed successful access to the anastomosis in 14 patients (87.5%), while the access failed in one type I and one type II BEG (12.5%). Mean time needed to access the anastomosis was 12.6 min (2-55 min). On a scale from 1–5, mean endoscopic difficulty score was 1.7. One patient (6.25%), with BEG type I, developed anastomotic stricture after 18 months that was successfully treated endoscopically by stenting. These preliminary results showed that, in relation to the other types, type III BEG demonstrated the tendency to be surgically simpler to perform, endoscopicall faster to access, easier and with no failure.
BEG, which is a modified biliary reconstruction, facilitates endoscopic access of the biliary anastomosis, offers management option for its complications, and, therefore, could be considered for biliary reconstruction of benign stricture. BEG type III tend to be surgically simpler and endoscopically faster, easier and more successful than type I and II.
PMCID: PMC3411507  PMID: 22720668
23.  Radiofrequency Ablation for Treating Liver Metastases from a Non-Colorectal Origin 
Korean Journal of Radiology  2011;12(5):579-587.
We wanted to assess the safety and efficacy of performing radiofrequency ablation (RFA) in patients with non-colorectal liver metastases.
Materials and Methods
In this retrospective study, 25 patients with 40 hepatic metastases (M:F = 17:8; mean age, 57 years; tumor size, 0.5-5.0 cm) from a non-colorectal origin (stomach, biliary, breast, pancreas, kidney and skin) were treated with RFA. The RFA procedures were performed using either an internally cooled electrode or a clustered electrode under ultrasound or CT guidance. Contrast-enhanced CT scans were obtained immediately after RFA and follow-up CT scans were performed within three months after ablation and subsequently at least every six months. The intrahepatic disease-free interval was estimated and the overall survival from the time of the initial RFA was analyzed using the Kaplan-Meier method.
No intraprocedural deaths occurred, but four major complications developed, including abscesses (n = 3) and pneumothorax (n = 1). Technical effectiveness was determined on the initial follow-up images. During the follow-up period (range, 5.9-68.6 months; median time, 18.8 months) for 37 tumors in 22 patients where technical effectiveness was achieved, 12 lesions (32%, 12 of 37) showed local tumor progression and new intrahepatic metastases occurred in 13 patients (59%, 13 of 22). The median intrahepatic disease-free interval was 10.1 months. The 1-year, 3-year and 5-year overall survival rates after RFA were 86%, 39% and 19%, respectively.
RFA showed intermediate therapeutic effectiveness for the treatment of non-colorectal origin liver metastases.
PMCID: PMC3168799  PMID: 21927559
Liver; Interventional procedures; Radiofrequency ablation; Preliminary clinical study
24.  Occult cystobiliary communication presenting as postoperative biliary leakage after hydatid liver surgery: Are there significant preoperative clinical predictors? 
Canadian Journal of Surgery  2006;49(3):177-184.
Occult cystobiliary communication (CBC) presents with biliary leakage, if the cystobiliary opening cannot be detected and repaired at operation. We investigated the clinical signs associated with the risk of occult CBC in the preoperative period by studying patients who developed biliary leakage after hydatid liver surgery.
We analyzed the records of 191 patients treated for hydatid liver cyst. Postoperative biliary leakage developed in 41 patients (21.5%). Independent predictive factors were established by logistic regression analysis using clinical parameters, whose cutoff values were determined by receiver operating characteristic (ROC) curves.
Postoperative biliary leakage presented as external biliary fistula in 31 (75.6%) of 41 patients, as biliary peritonitis in 6 (14.6%) and as cyst cavity biliary abscess in 4 (9.8%). Independent clinical predictors of occult CBC, represented by biliary leakage, were alkaline phosphatase > 250 U/L, total bilirubin > 17.1 μmol/L, direct bilirubin > 6.8 μmol/L, γ-glutamyl transferase > 34.5 U/L, eosinophils > 0.09 and cyst diameter > 8.5 cm. Multilocular or degenerate cysts increased the risk of biliary leakage (p = 0.012). Postoperative complication rates were 53.7% in the patients with biliary leakage, and 10.0% (p < 0.001) in those without. The mean postoperative hospital stay was longer in patients with biliary leakage (14.3 [and standard deviation {SD} 1.9] d) than in those without (7.3 [SD 2.3] d) (p < 0.001). Nineteen (61.3%) of 31 biliary fistulae closed spontaneously within 10 days. The remaining 12 (38.7%) fistulae closed within 7 days after endoscopic sphincterotomy.
Factors that predict occult CBC due to hydatid liver cyst were identified. These factors should allow the likelihood of CBC to be determined and, thus, indicate the need for additional procedures during operation to prevent the complications of biliary leakage.
PMCID: PMC3207592  PMID: 16749978
25.  Therapeutic effect of high-intensity focused ultrasound combined with transarterial chemoembolisation for hepatocellular carcinoma <5 cm: comparison with transarterial chemoembolisation monotherapy—preliminary observations 
The British Journal of Radiology  2012;85(1018):e940-e946.
To retrospectively compare the therapeutic effects of combined high-intensity focused ultrasound (HIFU) and transarterial chemoembolisation (TACE) with TACE alone for the treatment of non-advanced hepatocellular carcinomas (HCCs) <5 cm.
We retrospectively reviewed the tumour responses of 32 HCCs of 25 patients who underwent combined HIFU and TACE, and 46 HCCs of 32 patients who underwent TACE only. The mean follow-up observation of the TACE+HIFU group was on average 31 months and that of the TACE group was 33 months. Those patients who had undergone any other treatment modality (including systemic chemotherapy) during the follow-up observation period were excluded. The therapeutic effects were classified according to the modified Response Evaluation Criteria In Solid Tumors (mRECIST): complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Additionally, we defined CR', PR', SD' and PD' as the therapeutic effects “per tumour”.
The disease control rate calculated using the RECIST criteria (CR+PR+SD/All) was 48% in the HIFU+TACE group and 47% in the TACE group (p=0.78, Fisher's exact test). The disease control rate “per tumour” (CR'+PR'+SD'/All) was 78% in the HIFU+TACE group and 54% in the TACE group (p=0.035, Fisher's exact test). In the HIFU+TACE group, no HIFU-related complications requiring treatment were observed. The median survival time was 57 months in TACE+HIFU group and 36 months in the TACE group (p=0.048).
This preliminary study shows that the combination therapy of HIFU and TACE is more effective than TACE monotherapy for treating HCCs <5 cm.
PMCID: PMC3474013  PMID: 22553305

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