Incidence of Occult Intrahepatic Metastasis in Hepatocellular Carcinoma Treated With Transplantation Corresponds to Early Recurrence Rates After Partial Hepatectomy

Aufhauser, David D.; Sadot, Eran; Murken, Douglas R.; Eddinger, Kevin C.; Hoteit, Maarouf; Abt, Peter L.; Goldberg, David S.; DeMatteo, Ronald P.; Levine, Matthew H.

doi:10.1097/sla.0000000000002135

Cited by 39 publications

(28 citation statements)

References 27 publications

(12 reference statements)

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“…Migration and invasion are the embodiment of tumor metastasis ability. Evidence shows that tumor metastasis occurs at an early stage ( 17 – 19 ), and suggests that early metastasis is one of the major causes of recurrence and poor prognosis after surgical resection ( 20 ). Moreover, several studies have reported that UTR can stimulate the migration and invasion of many malignant cell lines.…”

Section: Discussionmentioning

confidence: 99%

Urotensin II receptor as a potential biomarker for the prognosis of hepatocellular carcinoma patients

Wei

Xue

et al. 2017

Oncology Letters

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Urotensin II and the associated urotensin II receptor (UTR) are important in the carcinogenesis of hepatocellular carcinoma (HCC). However, the clinical significance of UTR remains to be elucidated. The aim of the present study was to investigate if UTR exhibits the potential to act as a biomarker to predict the prognosis of HCC patients. The effects of UTR on motility and invasion of HCC cells were additionally investigated. UTR expression levels were determined by immunohistochemistry, in 83 HCC patients that previously underwent curative liver resection. The association between UTR levels and clinicopathological data were analyzed. In vitro, the expressions of UTR in QSG-7701, BEL-7402 and MHCC-97H cell lines were determined via western blotting. Small interfering (si)RNA was used to downregulate UTR in BEL-7402 and MHCC-97H cell lines, and the effects of UTR on tumor cell motility were tested by Transwell assay. UTR expression was associated with tumor number, size, histology and tumor node metastasis/Barcelona Clinic Liver Cancer HCC stage. UTR expression levels were additionally associated with recurrence-free and overall survival in HCC patients by Kaplan-Meier curve analysis (P<0.0001). In vitro, UTR expression levels were increased in BEL-7402 and MHCC-97H cell lines, compared with QSG-7701 (P<0.05). siRNA-mediated silencing of the UTR gene significantly inhibited cell motility in BEL-7402 and MHCC-97H cells. The results indicated that UTR may be regarded as a novel biomarker to predict outcomes following radical liver resection and as a potential therapeutic target to inhibit invasion and metastasis of HCC.

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Section: Discussionmentioning

confidence: 99%

Urotensin II receptor as a potential biomarker for the prognosis of hepatocellular carcinoma patients

Wei

Xue

et al. 2017

Oncology Letters

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“…Most notably, we found that expression in TFL was associated with faster and more HCC recurrence as well as worse patient survival after tumor resection. Aufhauser et al (38) hypothesized that early HCC recurrence (< 2 years) after tumor resection in HCC patients is the consequence of occult multi-focality present at the time of tumor resection, but failed to nd markers to identify such occult metastases. The 2-year recurrence rate in our cohort was signi cantly higher in patients with CTA-expression in TFL compared to patients without CTA-expression in TFL.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cancer testis Antigens in Tumor-adjacent Normal Liver Predicts Post-resection Recurrence of Hepatocellular Carcinoma

Noordam

Ozturk

et al. 2020

Preprint

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Background: High recurrence rates after resection of hepatocellular cancer (HCC) with curative intent and lack of effective therapy for advanced disease impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims of this study were to establish a panel of CTAs that are frequently and selectively expressed in tumors of HCC-patients, and to investigate whether CTAs might be expressed in tumor-free liver tissues of HCC-patients.Methods: Surgically-resected tumor and paired tumor-free (TFL) tissues of HCC patients (n=100), healthy livers (n=21), and other healthy tissues (n=22 different tissues) were assessed for mRNA expression of 49 carefully selected CTAs by RT-qPCR. Protein expression of 5 CTAs was determined by immunohistochemistry (n=78).Results: Twelve CTAs were expressed at mRNA level in ≥10% of HCC-tumor tissues and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein expression was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA expression in TFL was an independent negative prognostic factor for HCC-recurrence and survival after tumor resection.Conclusions: We established a novel panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients, that can be safely used for immunotherapeutic targeting of HCC. The increased risk of HCC recurrence in patients with CTA expression in TFL suggests that CTA-expressing (pre-)malignant cells may be a source of HCC recurrence. Therefore, immunotherapeutic targeting of these antigens should be considered as adjuvant therapy to prevent HCC-recurrence after tumor resection. Lay summary:Expression of multiple defined cancer testis antigens in non-cancerous liver tissue is associated with significantly increased cancer-recurrence and worse patient survival after tumor resection. We propose that immunotherapeutic targeting of these antigens may prevent HCC recurrence after tumor resection.

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“…71 Although increasingly advanced imaging and other techniques are being used to improve detection, as described above, the recurrence of HCC after resection is near 50% in the first few years following resection, mostly likely due to the presence of occult HCC in the remaining liver. 72 In contrast, recurrence after transplantation has been reported to be in the range of 11-18%. 73 Because of the limited supply of deceased donors, or the potential risk to a living donor, it is imperative to minimise recurrence, optimise outcomes, and maximise benefit through careful selection of appropriate recipients.…”

Section: Transplantation For Hccmentioning

confidence: 99%

Advances in resection and transplantation for hepatocellular carcinoma

Vibert

Schwartz

Olthoff

2020

Journal of Hepatology

130

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It would be impossible to summarise all of the significant developments in the surgical management of hepatocellular carcinoma (HCC), even just over the past year, in a manuscript of this scope. Thus, we have selected topics for discussion that are the subject of current controversy and have attempted to present balanced points of view. Hepatic resection and transplantation are both mature modalities, and for the most part technical advances and improvements in candidate selection are incremental. The ability to readily cure hepatitis C stands out as the most impactful development in the field over recent years, especially in Western countries where hepatitis C has long been the chief aetiology underlying HCC and a predictor of poor outcomes after surgery, but its full implications remain to be clarified. The rising incidence of non-alcoholic steatohepatitis-related HCC and what it means with regard to surgical HCC management is an area of great current interest. With advancing technology, non-surgical locoregional treatments are gaining increasing application as potentially curative therapies. In addition, the advances in molecular and genomic assessment of HCC hold promise for personalising treatment and prognostication. The possible role of immunotherapy as an adjuvant to resection is being aggressively investigated. While liver surgery maintains an important role, the care of patients with HCC is more and more a team effort and needs to take place in the context of a well-integrated interdisciplinary programme to achieve the best outcomes for patients.

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Incidence of Occult Intrahepatic Metastasis in Hepatocellular Carcinoma Treated With Transplantation Corresponds to Early Recurrence Rates After Partial Hepatectomy

Cited by 39 publications

References 27 publications

Urotensin II receptor as a potential biomarker for the prognosis of hepatocellular carcinoma patients

Urotensin II receptor as a potential biomarker for the prognosis of hepatocellular carcinoma patients

Expression of Cancer testis Antigens in Tumor-adjacent Normal Liver Predicts Post-resection Recurrence of Hepatocellular Carcinoma

Advances in resection and transplantation for hepatocellular carcinoma

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