Ronnie Tp Poon

Lyso-thermosensitive liposomal doxorubicin: a novel approach to enhance efficacy of thermal ablation of liver cancer.

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. No more than 30% of HCC patients receive curative treatment. Factors limiting curative therapy include tumor size and degree of liver impairment. Objective: To develop a cure for medium (3.1 – 5.0 cm) and large ( > 5 cm) tumors in seriously impaired livers. Method: Combine radiofrequency ablation (RFA) with lyso-thermosensitive liposomal doxorubicin (LTLD). Results/conclusions: RFA is used safely in patients with medium/large tumors and severe liver impairment; unclear tumor margins limit its curative efficacy. LTLD concentrates in the liver, where the anti-HCC chemotherapeutic, doxorubicin, is released into tumor margins by hyperthermia. RFA/LTLD can treat Child-Pugh class A-B patients with tumors up to 7 cm, a substantial increase in curable patients.

Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters

BackgroundSurgical resection is one important curative treatment for hepatocellular carcinoma (HCC), but the prognosis following surgery differs substantially and such large variation is mainly unexplained. A review of the literature yields a number of clinicopathologic parameters associated with HCC prognosis. However, the results are not consistent due to lack of systemic approach to establish a prediction model incorporating all these parameters.MethodsWe conducted a retrospective analysis on the common clinicopathologic parameters from a cohort of 572 ethnic Chinese HCC patients who received curative surgery. The cases were randomly divided into training (n = 272) and validation (n = 300) sets. Each parameter was individually tested and the significant parameters were entered into a linear classifier for model building, and the prediction accuracy was assessed in the validation setResultsOur findings based on the training set data reveal 6 common clinicopathologic parameters (tumor size, number of tumor nodules, tumor stage, venous infiltration status, and serum α-fetoprotein and total albumin levels) that were significantly associated with the overall HCC survival and disease-free survival (time to recurrence). We next built a linear classifier model by multivariate Cox regression to predict prognostic outcomes of HCC patients after curative surgery This analysis detected a considerable fraction of variance in HCC prognosis and the area under the ROC curve was about 70%. We further evaluated the model using two other protocols; leave-one-out procedure (n = 264) and independent validation (n = 300). Both were found to have excellent prediction power. The predicted score could separate patients into distinct groups with respect to survival (p-value = 1.8e-12) and disease free survival (p-value = 3.2e-7).ConclusionThis described model will provide valuable guidance on prognosis after curative surgery for HCC in clinical practice. The adaptive nature allows easy accommodation for future new biomarker inputs, and it may serve as the foundation for future modeling and prediction for HCC prognosis after surgical treatment.

Lyso-thermosensitive liposomal doxorubicin: an adjuvant to increase the cure rate of radiofrequency ablation in liver cancer

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. No more than 30% of HCC patients are considered suitable for curative treatment because of tumor size and severity of liver impairment, among other factors. Radiofrequency ablation (RFA) monotherapy can cure small (<3 cm) HCC tumors. An adjuvant that interacts synergistically with RFA might enable curative therapy for many HCC patients with lesions >3 cm. Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of the heat-enhanced cytotoxic doxorubicin within a heat-activated liposome. LTLD is infused intravenously prior to RFA. When heated to >39.5°C, LTLD releases doxorubicin in high concentrations into the tumor and the tumor margins. The RFA plus LTLD combination has shown a statistically significant dose-response effect for time to treatment failure in a Phase I trial in which most subjects (62.5%) had tumors >3 cm. RFA plus LTLD is currently being evaluated in a 600-patient randomized, double-blind, dummy-controlled trial.

High-intensity focused ultrasound ablation: An effective bridging therapy for hepatocellular carcinoma patients

AIM To analyze whether high-intensity focused ultrasound (HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma (HCC). METHODS From January 2007 to December 2010, 49 consecutive HCC patients were listed for liver transplantation (UCSF criteria). The median waiting time for transplantation was 9.5 mo. Twenty-nine patients received transarterial chemoembolization (TACE) as a bringing therapy and 16 patients received no treatment before transplantation. Five patients received HIFU ablation as a bridging therapy. Another five patients with the same tumor staging (within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison. Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores, tumor size and number, and cause of cirrhosis. RESULTS The HIFU group and TACE group showed no difference in terms of tumor size and tumor number. One patient in the HIFU group and no patient in the TACE group had gross ascites. The median hospital stay was 1 d (range, 1-21 d) in the TACE group and two days (range, 1-9 d) in the HIFU group (P < 0.000). No HIFU-related complication occurred. In the HIFU group, nine patients (90%) had complete response and one patient (10%) had partial response to the treatment. In the TACE group, only one patient (3%) had response to the treatment while 14 patients (48%) had stable disease and 14 patients (48%) had progressive disease (P = 0.00). Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list (P = 0.559). CONCLUSION HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis. It may reduce the drop-out rate of liver transplant candidate.

Rapid measurement of indocyanine green retention by pulse spectrophotometry: A validation study in 70 patients with Child-Pugh A cirrhosis before hepatectomy for hepatocellular carcinoma

BACKGROUND The indocyanine green (ICG) retention test is the most popular liver function test for selecting patients for major hepatectomy. Traditionally, it is done using spectrophotometry with serial blood sampling. The newly-developed pulse spectrophotometry is a faster alternative, but its accuracy on Child-Pugh A cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma has not been well documented. This study aimed to assess the accuracy of the LiMON(®), one of the pulse spectrophotometry systems, in measuring preoperative ICG retention in these patients and to devise an easy formula for conversion of the results so that they can be compared with classical literature records where ICG retention was measured by the traditional method. METHODS We measured the liver function of 70 Child-Pugh A cirrhotic patients before hepatectomy for hepatocellular carcinoma from September 2008 to January 2009. ICG retention at 15 minutes measured by traditional spectrophotometry (ICGR15) was compared with ICG retention at 15 minutes measured by the LiMON (ICGR15(L)). RESULTS The median ICGR15 was 14.7% (5.6%-32%) and the median ICGR15(L) was 10.4% (1.2%-28%). The mean difference between them was -4.3606. There was a strong correlation between ICGR15 and ICGR15(L) (correlation coefficient, 0.844; 95% confidence interval, 0.762-0.899). The following formula was devised: ICGR15=1.16XICGR15(L)+2.73. CONCLUSIONS The LiMON provides a fast and repeatable way to measure ICG retention at 15 minutes, but with constant underestimation of the real value. Therefore, when comparing results obtained by traditional spectrophotometry and the LiMON, adjustment of results from the latter is necessary, and this can be done with a simple mathematical calculation using the above formula.

Pancreaticoduodenectomy with vascular reconstruction for adenocarcinoma of the pancreas with borderline resectability.

AIM To analyze whether pancreaticoduodenectomy with simultaneous resection of tumor-involved vessels is a safe approach with acceptable patient survival. METHODS Between January 2001 and March 2012, 136 patients received pancreaticoduodenectomy for adenocarcinoma at our hospital. Seventy-eight patients diagnosed with pancreatic head carcinoma were included in this study. Among them, 46 patients received standard pancreaticoduodenectomy (group 1) and 32 patients received pancreaticoduodenectomy with simultaneous resection of the portal vein or the superior mesenteric vein or artery (group 2) followed by reconstruction. The immediate surgical outcomes and survivals were compared between the groups. Fifty-five patients with unresectable adenocarcinoma of the pancreas without liver metastasis who received only bypass operations (group 3) were selected for additional survival comparison. RESULTS The median ages of patients were 67 years (range: 37-82 years) in group 1, and 63 years (range: 35-86 years) in group 2. All group 2 patients had resection of the portal vein or the superior mesenteric vein and three patients had resection of the superior mesenteric artery. The pancreatic fistula formation rate was 21.7% (10/46) in group 1 and 15.6% (5/32) in group 2 (P = 0.662). Two hospital deaths (4.3%) occurred in group 1 and one hospital death (3.1%) occurred in group 2 (P = 0.641). The one-year, three-year and five-year overall survival rates in group 1 were 71.1%, 23.6% and 13.5%, respectively. The corresponding rates in group 2 were 70.6%, 33.3% and 22.2% (P = 0.815). The one-year survival rate in group 3 was 13.8%. Pancreaticoduodenectomy with simultaneous vascular resection was safe for pancreatic head adenocarcinoma. CONCLUSION The short-term and survival outcomes with simultaneous resection were not compromised when compared with that of standard pancreaticoduodenectomy.

Genomic and proteomic biomarkers for diagnosis and prognosis of hepatocellular carcinoma

Hepatocellular carcinoma is one of the most deadly liver malignancies found worldwide, with hepatitis virus infection being the prominent risk factor for this lesion. Patients with hepatocellular carcinoma are usually first diagnosed when in the advanced stage; thus, long-term clinical outcomes are poor and patients have limited treatment options. Currently, surveillance of hepatocellular carcinoma relies upon serological testing of alpha-fetoprotein levels and hepatic ultrasonography, which have low sensitivity and specificity, and are sometimes operator-dependent, respectively. Therefore, discovery of new biomarkers for early and accurate detection of hepatocellular carcinoma would be of great clinical value. Genomic and proteomic approaches are two major laboratory platforms for the identification of candidate hepatocellular carcinoma biomarkers based on profiling and validating with tumor and nontumor clinical samples. Frequently, these diagnostic markers have been found in association with genetic aberrations, protein-level alterations, post-translational modifications and immune functions. With the discovery of these biomarkers, earlier detection of hepatocellular carcinoma in high-risk subjects (e.g., cirrhosis and hepatitis carriers) becomes possible, which will enable clinicians to offer patients better clinical management and more effective treatment modalities.

Little girl who conquered the "ALPPS''

An insufficient future liver remnant (FLR) is associated with post-hepatectomy liver failure. Associating liver partition and portal vein ligation for stage hepatectomy (ALPPS) has been shown to be effective for the induction of rapid FLR hypertrophy so as to improve the resectability in patients with insufficient FLR. We hereby report our experience of this novel approach for a 6-year-old patient with hepatoblastoma. Computed tomography showed a hepatoblastoma measuring 12.5 cm × 9.9 cm × 11.7 cm in the right liver (Couinaud segment IV, V and VIII). Volumetric assessment of the FLR i.e., left lateral section was 112.6 mL i.e., 21.2% of the estimated total liver volume. In view of the small-for-size FLR, ALPPS was contemplated. An anterior approach was adopted for the in-situ parenchymal split without mobilisation of the right liver. FLR volumetry on the seventh postoperative day was 160.7 mL, which represented a 46.1% gain in volume, and a FLR/ESLV ratio of 30.2%. A right trisectionectomy was performed on the eighth postoperative day. Postoperative recovery was uneventful. Patient was discharged on day 16 after the first operation. To our knowledge, this was the first report that showed the applicability of ALPPS to a paediatric patient.

Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases

BACKGROUND Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma. METHODS A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications. RESULTS Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication. CONCLUSIONS Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.

Is radiofrequency ablation the treatment of choice for patients with small hepatocellular carcinoma

Liver resection is widely considered the mainstay of curative therapy for small hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) was initially developed as a treatment for small HCC in patients with considerable cirrhosis and inadequate liver function reserve for liver resection. However, in some centers, RFA is now used for small HCC, as an alternative to liver resection or even as the preferred treatment. This Practice Point commentary discusses the findings and limitations of a retrospective cohort study by Livraghi et al. that analyzed the outcomes of a group of patients with small, single HCC who underwent treatment with RFA. The authors reported a low major complication rate and a local complete response rate similar to that after resection. This commentary highlights the issues to consider when interpreting and generalizing these results, in particular that these findings need to be interpreted in the light of studies that suggest a high rate of local recurrence and incomplete histopathological response after RFA of small HCC.