Histological Heterogeneity of Primary Liver Cancers: Clinical Relevance, Diagnostic Pitfalls and the Pathologist’s Role

Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA. Combined HCC-CCA and small duct type iCCA show similar clinical presentations, and their histological features are more complex than seen in HCC. Therefore, while their treatment strategy differs, it is difficult to properly diagnose these tumors. Currently, HCC is the only tumor that can be treated by liver transplantation. In addition, small duct type iCCA harbors IDH1/2 mutations and FGFR2 fusions, which can be used for targeted therapy. Thus, improving diagnostic accuracy is crucial. A further point to note is that PLCs often present as multiple liver tumors, and they can be a combination of different types of PLCs or HCCs. In the case of HCCs, two different scenarios are possible, namely intrahepatic metastasis, or multicentric occurrence. Therefore, it is essential to characterize the type of multiple liver tumors. This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCA, including their diagnostic pitfalls and clinical relevance. It is designed to be of use to clinicians who are dealing with PLCs, to provide a better understanding of the pathology of these tumors, and to enable a more accurate diagnosis and optimal treatment choice.

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Hepatic resection in children: highlighted and revisited steps

Egyptian Pediatric Association Gazette ◽

10.1186/s43054-019-0008-4 ◽

2019 ◽

Vol 67 (1) ◽

Author(s):

Hesham Mohammed Abdelkader ◽

Mohamed Abdel-Latif ◽

Mohamed Abdelsattar ◽

Ahmed Abdelhaseeb Youssef

Keyword(s):

Blood Loss ◽

Liver Tumors ◽

University Hospital ◽

Remnant Liver ◽

Vascular Control ◽

Biliary Leak ◽

Intraoperative Bleeding ◽

Male Predominance ◽

Different Types ◽

Minimize Blood Loss

Abstract Background Hepatectomy in children deserves exhaustive preoperative and intraoperative tools to define the anatomy, minimize blood loss, and confirm adequacy of liver tissue left. The aim of this study is to report our experience in surgical management of liver tumors. Results All liver resections performed in Ain-Shams University Hospital, by the same team, between July 2013 and June 2018 were retrospectively reviewed. Data related to basic demographics, indication for resection, methods of parenchymal resection, blood loss, hospital stay, morbidity, and mortality was collected. The study included 27 patients who underwent different types of hepatectomies. There was a male predominance. Age ranged from 6 months to 13 years. Weight ranged from 5.7 to 33.7 kg. Total operative time ranged from 68 to 322 min, while resection time ranged from 34 to 144 min. Blood loss ranged from 53 to 259 ml. Surgical morbidities included five patients with minor biliary leak, three patients had surgical site infection, and one patient had torsion of the remnant liver necessitating repositioning. Recurrence of the mass was faced in three patients with hepatoblastoma. There were two mortalities; one occurred as a sequela of massive intraoperative bleeding and the other took place due to postoperative hepatic insufficiency. Conclusion For a safe hepatectomy, thorough familiarity of the hepatic segmental anatomy together with the various techniques for parenchymal resection and vascular control is fundamental. Complications such as biliary leak and torsion of remnant can be easily avoided by simple measures.

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Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy

Cancers ◽

10.3390/cancers13071537 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1537

Author(s):

Stephan Walrand ◽

Michel Hesse ◽

Philippe d’Abadie ◽

François Jamar

Keyword(s):

Animal Studies ◽

Liver Tumors ◽

Clinical Trial Design ◽

Normal Liver ◽

Dose Ratio ◽

Liver Cancers ◽

Tumoral Cell ◽

Flow Enhancement ◽

Curative Intention ◽

Tumoral Cells

Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.

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Effect of Erosive pH Cycling on Different Restorative Materials and on Enamel Restored with These Materials

Operative Dentistry ◽

10.2341/07-77 ◽

2008 ◽

Vol 33 (2) ◽

pp. 203-208 ◽

Cited By ~ 33

Author(s):

L. F. Francisconi ◽

H. M. Honório ◽

D. Rios ◽

A. C. Magalhães ◽

M. A. A. M. Machado ◽

...

Keyword(s):

Clinical Relevance ◽

Restorative Material ◽

Tooth Erosion ◽

Different Types ◽

Restorative Materials ◽

Ph Cycling

Clinical Relevance The different types of restorative materials tested were not able to protect adjacent enamel from erosion. Thus, the ability of a restorative material to prevent tooth erosion should not be considered when choosing a material.

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Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Digestive Disease Interventions ◽

10.1055/s-0040-1712083 ◽

2020 ◽

Vol 04 (02) ◽

pp. 187-194

Author(s):

Shauna R. Campbell ◽

Timothy D. Smile ◽

Sarah M.C. Sittenfeld ◽

Kevin L. Stephans

Keyword(s):

Hepatocellular Carcinoma ◽

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Primary Liver Cancer ◽

Effective Treatment Option ◽

Stereotactic Body Radiation ◽

Common Cancer ◽

Clinical Presentations ◽

Liver Cancers ◽

Bridging To Transplant

AbstractPrimary liver cancer is the seventh most common cancer worldwide and is the second leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for three-quarters of primary liver cancers and less than a third of patients present with curable disease. Liver-directed therapy is essential for the treatment of patients with unresectable HCC and the advancement of stereotactic body radiation therapy (SBRT) has made radiation a safe and effective treatment option in a range of clinical presentations. In this review, we discuss the technical aspects of SBRT and the general approach to treatment of HCC. We explore the use of SBRT for bridging to transplant, downstaging, and the treatment of large tumors and portal vein tumor thrombus. Although there is limited high-quality randomized data, we review the evidence comparing SBRT with other liver-directed therapies and explore areas for future investigation.

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Primary Hepatic Angiosarcoma: A Rare Liver Malignancy – Varying Manifestations but Grave Prognosis

Case Reports in Gastroenterology ◽

10.1159/000506928 ◽

2020 ◽

Vol 14 (1) ◽

pp. 137-149 ◽

Cited By ~ 1

Author(s):

Natthapat Rujeerapaiboon ◽

Panu Wetwittayakhlang

Keyword(s):

Liver Tumors ◽

Case Series ◽

High Rate ◽

Therapeutic Approaches ◽

Tumor Rupture ◽

Liver Malignancies ◽

Liver Malignancy ◽

Hepatic Angiosarcoma ◽

Clinical Presentations ◽

Primary Hepatic Angiosarcoma

Primary hepatic angiosarcoma (PHA) is a rare mesenchymal liver tumor, accounting for 0.1–2% of primary liver malignancies. The clinical presentations of PHA are variable, from asymptomatic to liver failure or complicated with tumor rupture. The diagnosis of PHA is difficult due to the lack of specific clinical manifestation and investigation results, which can be confused with other liver tumors resulting in late diagnosis. However, there is currently a paucity of effective therapeutic approaches. We advocate early diagnosis with radiological imaging and histopathology because most of them are diagnosed in late-stage and carry a grave prognosis. Surgical resection remains the mainstay of treatment, which can significantly prolong survival. Chemotherapy, including transarterial chemoembolization, is an option for palliative treatment. Unfortunately, molecular treatment has limited efficacy and liver transplantation is also not recommended due to high rate of recurrence. We present a case series of four patients with biopsy-proven PHA which had distinct presentations and clinical courses.

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Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

Diagnostics ◽

10.3390/diagnostics10020078 ◽

2020 ◽

Vol 10 (2) ◽

pp. 78 ◽

Cited By ~ 1

Author(s):

Yewei Liu ◽

Shuncong Wang ◽

Xiaohui Zhao ◽

Yuanbo Feng ◽

Guy Bormans ◽

...

Keyword(s):

Clinical Trials ◽

Liver Cancer ◽

Human Liver ◽

Cellular Differentiation ◽

Liver Tumors ◽

Pancreatic Tumors ◽

Imaging Biomarkers ◽

Vascular Disrupting Agents ◽

Liver Cancers ◽

Vascular Disrupting

Vascular disrupting agents (VDAs) have entered clinical trials for over 15 years. As the leading VDA, combretastatin A4 phosphate (CA4P) has been evaluated in combination with chemotherapy and molecular targeting agents among patients with ovarian cancer, lung cancer and thyroid cancer, but still remains rarely explored in human liver cancers. To overcome tumor residues and regrowth after CA4P monotherapy, a novel dual targeting pan-anticancer theragnostic strategy, i.e., OncoCiDia, has been developed and shown promise previously in secondary liver tumor models. Animal model of primary liver cancer is time consuming to induce, but of value for more closely mimicking human liver cancers in terms of tumor angiogenesis, histopathological heterogeneity, cellular differentiation, tumor components, cancer progression and therapeutic response. Being increasingly adopted in VDA researches, multiparametric magnetic resonance imaging (MRI) provides imaging biomarkers to reflect in vivo tumor responses to drugs. In this article as a chapter of a doctoral thesis, we overview the construction and clinical relevance of primary and secondary liver cancer models in rodents. Target selection for CA4P therapy assisted by enhanced MRI using hepatobiliary contrast agents (CAs), and therapeutic efficacy evaluated by using MRI with a non-specific contrast agent, dynamic contrast enhanced (DCE) imaging, diffusion weighted imaging (DWI) are also described. We then summarize diverse responses among primary hepatocellular carcinomas (HCCs), secondary liver and pancreatic tumors to CA4P, which appeared to be related to tumor size, vascularity, and cellular differentiation. In general, imaging-histopathology correlation studies allow to conclude that CA4P tends to be more effective in secondary liver tumors and in more differentiated HCCs, but less effective in less differentiated HCCs and implanted pancreatic tumor. Notably, cirrhotic liver may be responsive to CA4P as well. All these could be instructive for future clinical trials of VDAs.

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SAT-476-Discordance between clinical judgement and genetic differentiation of intrahepatic metastasis and multicentric occurrence in multinodular HCC

Journal of Hepatology ◽

10.1016/s0618-8278(19)31683-4 ◽

2019 ◽

Vol 70 (1) ◽

pp. e843

Author(s):

Yuji Iimuro ◽

Atsushi Takano ◽

Kenji Amemiya ◽

Yosuke Hirotsu ◽

Hitoshi Mochizuki ◽

...

Keyword(s):

Genetic Differentiation ◽

Intrahepatic Metastasis ◽

Clinical Judgement ◽

Multicentric Occurrence

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Embolotherapy for Hepatic Oncology: Current Perspectives and Future Directions

Digestive Disease Interventions ◽

10.1055/s-0040-1712146 ◽

2020 ◽

Vol 04 (02) ◽

pp. 134-147

Author(s):

Raazi Bajwa ◽

David C. Madoff ◽

Sirish A. Kishore

Keyword(s):

Artificial Intelligence ◽

Liver Tumors ◽

Transarterial Embolization ◽

Supportive Evidence ◽

Selective Internal Radiotherapy ◽

Future Directions ◽

Locoregional Treatment ◽

Internal Radiotherapy ◽

Liver Cancers ◽

Bland Embolization

AbstractPrimary and secondary liver cancers are a major cause of mortality worldwide. Transarterial liver-directed therapy, or embolotherapy, represents an important locoregional treatment strategy for primary and secondary liver tumors. Embolotherapeutic modalities include bland embolization (transarterial embolization), chemoembolization (transarterial chemoembolization), and radioembolization or selective internal radiotherapy. A brief technical overview of embolotherapeutic modalities as well as supportive evidence for the treatment of most common primary and secondary liver tumors will be discussed in this review. Several potential future applications, including synergy with systemic therapy, interventional theranostics, and artificial intelligence will also be reviewed briefly.

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Induction of hypertrophy of the left hepatic lobe by unilateral right hepatic arterial radioembolization (RE) using 90Y-labeled resin microspheres in patients with right-sided secondary malignant liver tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14630 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14630-e14630

Author(s):

Benjamin Garlipp ◽

Max Seidensticker ◽

Romy Irmscher ◽

Robert Damm ◽

Jens Ricke ◽

...

Keyword(s):

Tumor Progression ◽

Liver Surgery ◽

Liver Tumors ◽

Prospective Trial ◽

Future Liver Remnant ◽

Similar Degree ◽

Simultaneous Treatment ◽

Liver Remnant ◽

Resin Microspheres ◽

Liver Cancers

e14630 Background: In patients with unilateral liver tumors who are candidates for extended liver resection but demonstrate insufficient future liver remnant (FLR) size, induction of FLR hypertrophy by contralateral portal vein embolization (PVE) is an established approach but concerns exist regarding tumor progression during the interval from PVE to liver surgery. We hypothesized that unilateral hepatic arterial radioembolization (RE) using 90Y-labelled resin microspheres achieves a similar degree of contralateral hypertrophy as PVE. Methods: 32 patients with right-sided secondary liver cancers (metastases from colorectal [n=20], breast [n=7], head and neck [n=2], and other [n=3] cancers) were treated with unilateral right hepatic arterial RE. Before and 44 (22-81) days following RE MRI-based volumetry of the total liver (TLV), the right (RLV, segments 4-8) and left (LLV, segments 2 and 3) hepatic lobes was performed. TLV, RLV, and LLV as well as the LLV/TLV ratio before and after RE were compared using the Mann-Whitney U-test. Results: Median values for TLV, RLV, LLV, and the LLV/TLV ratio are shown in table. Compared to baseline, RLV and TLV showed no significant change after right hepatic arterial RE (-3.7 [min/max, -37.7/+56.5] per cent [p=0.158] and +3.2 [-16.5/+47.4] per cent [p=0.282], respectively). In contrast, LLV as well as the LLV/TLV ratio were significantly increased after RE (+34.9 [-3.1/+146.2] per cent [p<0.001] and +29.4 [-24.3/+155.3] per cent [p<0.001], respectively). Conclusions: Right hepatic arterial RE achieved superior contralateral liver hypertrophy compared to hypertrophy reported after PVE and may be an alternative to PVE since it provides simultaneous treatment to the liver tumors during the interval from treatment to liver surgery, reducing the risk for tumor progression. These two methods should be directly compared within a prospective trial. [Table: see text]

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Complications of thermal ablation of hepatic tumors: Comparison of radiofrequency and microwave techniques.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15040 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15040-e15040 ◽

Cited By ~ 1

Author(s):

Xiang Jing ◽

Jianmin Ding ◽

Jibin Liu ◽

Yandong Wang ◽

Fengmei Wang ◽

...

Keyword(s):

Liver Cancer ◽

Thermal Ablation ◽

Liver Tumors ◽

Major Complication ◽

Mortality Rates ◽

Complication Rates ◽

Hepatic Tumors ◽

Ablation Therapy ◽

Liver Cancers ◽

Significant Difference

e15040 Background: The efficacy and safety of radiofrequency ablation (RFA) have been reported in the literatures, which are considered as frontline choice for treatment of liver cancer. Recently, microwave ablation (MWA) has emerged and gained great attention over RFA. However, in comparison to RFA, the safety of MWA for treatment of liver cancer has not been fully reported in the literatures. Studies with large clinical data sets are still needed to understand the technique and avoid the complications. The objective of this study was to retrospectively investigate the common complications of thermal ablations of liver tumors using both RFA and MWA techniques, and compare the safety between these two procedures. Methods: This retrospective study protocol was approved by our institutional ethics committee to allow investigators to review the existing patient’s medical records. A total of 879 patients with hepatic tumors underwent thermal ablation. There were 323 cases having the RFA procedures and 556 cases having MWA procedures. The complications of thermal ablations of liver tumors were compared using both RFA and MWA techniques. Results: A total of 1,030 thermal ablation sessions was performed in 879 patients with a total of 1,652 tumors. There were 323 patients with 562 tumors received a total of 376 RFA with averaged 1.16±0.48 sessions per patient. The other 556 patients with 1,090 tumors received a total of 654 MWA with averaged1.18±0.51 sessions per patient. The mortality rates were 0.31% (1/323) and 0.36% (2/556) in RFA and MWA group. In RFA and MWA group, the major complication rates were 3.5% (13/376) and 3.1% (20/654) (Table 1), meanwhile the minor complication rates were 5.9% (22/376) and 5.7% (37/654). There was no statistical significant difference for the mortality rates, the major complications, the minor complications between the RFA and MWA groups (P>0.05). Conclusions: Thermal ablation therapy in the treatment of liver cancers is relatively safe with low mortality and low incidence of serious complications. The types and incidences of complications caused by RFA and MWA are similar and comparable for safety consideration in clinical settings.

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