Liver resection of transplantation for hepatocellular carcinoma?: Restrospective analysis of 215 patients with cirrhosis

doi:10.1016/S0168-8278(97)80462-X

Journal of Hepatology

Volume 26, Issue 6, July 1997, Pages 1274-1280

https://doi.org/10.1016/S0168-8278(97)80462-X Get rights and content

Abstract

Background/Aims: Currently, surgical treatment of hepatocellular carcinoma in patients with cirrhosis is not clearly defined. The objective of this study was, in patients with cirrhosis with hepatocellular carcinoma, to compare liver resection to transplantation assessed by patient survival and to determine whether the tumor recurrence might be influenced by prognostic factors.

Methods: We have gathered all the available data from six French Medical Universities, for 215 patients with cirrhosis with hepatocellular carcinoma surgically treated either by liver resection (102) or by transplantation (113).

Results: The overall 5-year survival rate was similar in the transplantation group and in the resection group (32% vs. 31%, p0.7). However, the 5-year survival rate without recurrence was higher in the transplantation group than in the resection group (60% vs. 14%, p<0.001). Three independent prognostic factors influenced significantly the survival without recurrence: the surgical treatment by transplantation (p<0.001), the number of tumors (p<0.01) and the tumor size (p<0.001). With these factors we defined a prognostic index (Ip) which allowed assessment of the probability of survival without recurrence: Ip(Xie.x1.41)+(Nbr T.x0.19)+(Size TV.x0.16); Xiesurgical treatment (XieO if transplantation, Xie1 if resection), Nbr.T. and Size TV.number of tumors and size of the most voluminous tumor, respectively, according to the histologic study.

Conclusions: These results and this prognostic index are encouraging for liver transplantation as treatment of hepatocellular carcinoma in selected patients with cirrhosis.

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Hepatocellular Carcinoma (HCC) still is one of the most detrimental malignant diseases in the world. As two curative surgical therapies exist, the discussion whether to opt for liver resection (LR) or transplantation (LT) is ongoing, especially as novel techniques to improve outcome have emerged for both. The aim of the study was to investigate how the utilization and outcome of the respective modalities changed through time.
We searched Medline and PubMed for relevant publications comparing LT and LR in HCC patients during the time period from 1990 to 2022, prior to March 31, 2023. A total of 63 studies involving 19,804 patients – of whom 8178 patients received a liver graft and 11,626 underwent partial hepatectomy - were included in this meta-analysis.
LT is associated with significantly better 5-year overall survival (OS) (64.83%) and recurrence-free survival (RFS) (70.20%) than LR (OS: 50.83%, OR: 1.79, p < 0.001; RFS: 34.46%, OR: 5.32, p < 0.001). However, these differences are not as evident in short-term intervals. Older cohorts showed comparable disparities between the outcome of the respective modalities, as did newer cohorts after 2005. This might be due to the similar improvement in survival rates that were observed for both, LT (15–23%) and LR (12–20%) during the last 30 years.
LT still outperforms LR in the therapy of HCC in terms of long-term survival rates. Yet, LR outcome has remarkably improved which is of major importance in reference to the well-known limitations that occur in LT.
Impact of radiation therapy and alpha-fetoprotein level on survival outcomes for patients with hepatocellular carcinoma: A population-based study
2023, Clinics and Research in Hepatology and Gastroenterology
The use of radiation therapy (RT) in hepatocellular carcinoma (HCC) remains a matter for debate. Recently published research indicate that advanced RT techniques may improve survival in patients with HCC. This study aimed to evaluate this hypothesis in a large-scale retrospective cohort. The effect of alpha-fetoprotein (AFP) was taken into account because of its important role in the prognosis of HCC.
The Surveillance, Epidemiology, and End Results (SEER) database was queried for adults patients diagnosed 2010–2019 with HCC (≥ 18 years). The study population was divided into four groups: Non-radiation & AFP-positive (reference), Non-radiation & AF-negative, Radiation & AFP-positive, Radiation & AFP-negative. Distant metastasis (DM) was used as a stratification factor. Differences in 5-year overall survival (OS) of the four groups were assessed using the Kaplan–Meier method. Univariate and multivariable Cox proportional hazards model were used to estimate unadjusted and adjusted hazard ratios (HR).
A total of 34,656 patients were eligible for this analysis, including 21,084 (60.8%), 8,449 (24.4%), 3,810 (11.0%) and 1,313 (3.8%) in the Non-radiation & AFP-positive, Non-radiation & AF-negative, Radiation & AFP-positive and Radiation & AFP-negative groups, respectively. Median OSs of the four groups were 3, 4, 5 and 11 months in the DM cohort, and 12, 28, 15, and 28 months in the Non-DM cohort. Patients in the Radiation & AFP - group had the best OS and patients in the Non-radiation & AFP + group had the worst OS (adjusted HR [95% confidence interval (CI)]: 0.497 [0.399–0.619] in the DM cohort, and 0.405 [0.372–0.441] in the Non-DM cohort). Radiation & AFP + also showed improved survival compared with the reference group (adjusted HR [95%CI]: 0.725 [0.657–0.801] in the DM cohort, and 0.630 [0.600–0.661] in the Non-DM cohort).
This population-based cohort study confirmed a significant improvement in overall survival with radiation therapy in HCC. AFP-negative patients benefit the most from RT. Superior OS of radiation therapy and AFP-negative status persisted even in patients with complex metastasis patterns. Our data suggest that radiation may provide an alternative modality for unresectable HCC.
Therapeutic Ultrasound Parameter Optimization for Drug Delivery Applied to a Murine Model of Hepatocellular Carcinoma
2021, Ultrasound in Medicine and Biology
Ultrasound and microbubble (USMB)-mediated drug delivery is a valuable tool for increasing the efficiency of the delivery of therapeutic agents to cancer while maintaining low systemic toxicity. Typically, selection of USMB drug delivery parameters used in current research settings are either based on previous studies described in the literature or optimized using tissue-mimicking phantoms. However, phantoms rarely mimic in vivo tumor environments, and the selection of parameters should be based on the application or experiment. In the following study, we optimized the therapeutic parameters of the ultrasound drug delivery system to achieve the most efficient in vivo drug delivery using fluorescent semiconducting polymer nanoparticles as a model nanocarrier. We illustrate that voltage, pulse repetition frequency and treatment time (i.e., number of ultrasound pulses per therapy area) delivered to the tumor can successfully be optimized in vivo to ensure effective delivery of the semiconducting polymer nanoparticles to models of hepatocellular carcinoma. The optimal in vivo parameters for USMB drug delivery in this study were 70 V (peak negative pressure = 3.4 MPa, mechanical index = 1.22), 1-Hz pulse repetition frequency and 100-s therapy time. USMB-mediated drug delivery using in vivo optimized ultrasound parameters caused an up to 2.2-fold (p < 0.01) increase in drug delivery to solid tumors compared with that using phantom-optimized ultrasound parameters.
Longitudinal assessment of ultrasound-guided complementary microRNA therapy of hepatocellular carcinoma
2018, Journal of Controlled Release
Hepatocellular carcinoma (HCC) is the second-leading cause of cancer related deaths worldwide and new strategies to efficiently treat HCC are critically needed. The aim of this study was to assess the longitudinal treatment effects of two complementary miRNAs (miRNA-122 and antimiR-21) encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA) - poly ethylene glycol (PEG) nanoparticles (PLGA-PEG-NPs), administered by an ultrasound-guided and microbubble-mediated delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Using in vitro assays, we show that repeated miRNA treatments resulted in gradual reduction of HCC cell proliferation and reversal of doxorubicin resistance. Optimized US parameters resulted in a 9–16 fold increase (p = 0.03) in miRNA delivery in vivo in HCC tumors after two US treatments compared to tumors without US treatment. Furthermore, when combined with doxorubicin (10 mg/kg), longitudinal miRNA delivery showed a significant inhibition of tumor growth in both resistant and non-resistant tumors compared to non-treated, and doxorubicin treated controls. We also found that ultrasound-guided miRNA therapy was not only effective in inhibiting HCC tumor growth but also allowed lowering the dose of doxorubicin needed to induce apoptosis. In conclusion, the results of this study suggest that ultrasound-guided and MB-mediated delivery of miRNA-122 and antimiR-21, when combined with doxorubicin, is a highly effective approach to treat resistant HCC while reducing doxorubicin doses needed for treating non-resistant HCC in longitudinal treatment experiments. Further refinement of this strategy could potentially lead to better treatment outcomes for patients with HCC.
Changing Paradigm in the Surgical Management of Hepatocellular Carcinoma With Salvage Transplantation
2018, Transplantation Proceedings
The objective of this study was to compare the long-term outcomes of primary and salvage liver transplantation for patients with hepatocellular carcinoma (HCC).
This was a 10-year retrospective analysis in a tertiary referral center.
There were 184 patients recruited (primary liver transplantation [pLT]:salvage liver transplantation [sLT], 143:41). The median follow-up time was 79 months. Operation time was shorter in the pLT group than the sLT group (661 ± 164 minutes vs 754 ± 206 minutes; P = .01) and the blood loss was 3749 mL and 3545 mL for pLT and sLT, respectively (P = .735). The reoperation rate was 5.6% and 4.9%, respectively (P = 1.0). The 5-year overall and disease-free survival rates from the time of transplantation for pLT and sLT were 84.1% versus 70.2% (P = .01) and 82.2% versus 65.8% (P = .01), respectively. The 5-year overall survival rate from the time of primary treatment for sLT was 80.3% (P = .1). Subgroup analysis of sLT showed that young age (50 vs 56 year old; P = .004) was the only factor associated with poor overall survival. Young age (P = .004) and microvascular permeation (P = .008) in the recurrent tumor were associated with HCC recurrence. Young age stands out to be the only independent factor associated with HCC recurrence.
sLT is the treatment of choice for patients with recurrent HCC in regions of graft shortage.
De novo hepatocellular carcinoma of liver allograft: A neglected issue
2015, Cancer Letters
Citation Excerpt :
Albeit this transplant policy has remarkably reduced the risk of recurrence, HCC reappears in approximately 20% of patients [6]. This is believed to derive from extrahepatic tumor-cell dissemination before OLT [6], leading to cancer resurfacing outside or, more frequently, within the liver [7–10]. However, another type of carcinogenesis may affect the graft, i.e. a de novo appearance of a secondary new HCC, independent of the tumor of the native liver.
De novo hepatocellular carcinoma (HCC) is a rare neoplasm, ensuing after liver transplantation. Its definitive identification requires sophisticated molecular analyses. Hence, some cases, particularly those ensuing in patients who have been transplanted with HCC, are probably misclassified as recurrences of the primary tumor. Nevertheless, a tumor recurrence cannot be excluded in patients transplanted without apparent malignancy, because of an occult HCC. The main risk factor for de novo HCC is the recurrence of hepatitis/cirrhosis in the allograft. All the described de novo HCCs occurred at least 2 years after OLT, whereas most recurrent HCCs develop within 2 years from surgery. The treatment of this tumor can follow the recommendations of guidelines for primary HCC and, unlike recurrent HCC, re-transplant can be considered a therapeutic option for these patients. Prevention of this tumor relies on the prevention/cure of recurrent liver disease in the allograft and on judicious post-transplant immunosuppression.
The present review analyzes this topic by addressing seven key questions. An algorithm based on clinical factors – regarding primary and secondary tumors – to trigger the suspicion of de novo origin of a post-transplant HCC is proposed.

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Liver resection of transplantation for hepatocellular carcinoma?: Restrospective analysis of 215 patients with cirrhosis

Abstract

Gastrenterology

Carcinomes hépatocellulaires en France.

Gastroenterol Clin Biol

Current treatment modalities for hepatocellular carcinoma

Ann Surg

Natural history of hepatocellular carcimona in relation to treatment.

Cancer

Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.

Ann Surg

Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy

Cancer

Postoperative recurrence of hepatocellular carcinoma.

Ann Surg

Assessment of pattern and treatment of intrahepatic recurrence after resection of hepatocellular carcinoma

Surg Gynecol Obstet

Résections des carcinomes hépatocellulaires, analyse des facteurs pronostiques d'une série multicentrique de 153 malades.

Gastroenterol Clin Biol

The role of liver transplantation in hepatobility malignancy.

Ann Surg