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Out of 10 cases of liver cancer, 7 have recurred. Small liver cancers should not be taken lightly either!

时间：2026-04-16　人气：

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# Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. According to epidemiological statistics, HCC ranks as the seventh largest tumor globally and is the second leading cause of cancer-related deaths [1]. With increasing emphasis on health check-ups and advancements in imaging technology, the diagnostic rate for primary small hepatocellular carcinoma (diameter ≤ 3cm) has continued to rise.

According to the diagnosis and treatment guidelines for early liver cancer issued by EASL and AASLD, the recommended radical treatment methods include surgical resection, ablation, and liver transplantation [2, 3]. Due to the scarcity of organ resources, the widespread application of liver transplantation is limited. Surgical resection is widely recommended as the first-line treatment for small hepatocellular carcinoma, with a 5-year survival rate of up to 60% [4]. However, 40% of patients still experience treatment failure due to recurrence or metastasis, which is currently the most urgent challenge to overcome in treatment.

liver caner

Tips for Comprehensive Treatment of Liver Cancer

There are six common standardized treatment methods for liver cancer, including hepatectomy, liver transplantation, ablation therapy, transcatheter arterial chemoembolization (TACE), radiotherapy, and systemic anti-tumor therapy. The choice of treatment method depends on factors such as the size, number, location, and liver function classification of the tumor. It is recommended to select appropriate treatment approaches for patients with liver cancer at different stages, and to combine multiple methods to achieve the best therapeutic effect.

The clinical treatment approach for small hepatocellular carcinoma has evolved from the traditional "single surgical resection" to the current comprehensive treatment that combines "local therapy with systemic therapy".

Transcatheter arterial chemoembolization

This method involves inserting a tube from the femoral artery in the lower limbs or the radial artery in the upper limbs to reach the liver, blocking the artery supplying the tumor, and causing ischemic necrosis of the tumor.

Chemical ablation

Usually, under the guidance of ultrasound or CT, anhydrous alcohol is injected into the tumor to rapidly dehydrate cells and denature and coagulate proteins, thereby killing tumor cells. However, this method is currently less commonly used.

Physical ablation

Including radiofrequency ablation and microwave ablation, which are also guided by ultrasound or CT, and utilize the heat generation effect of puncture needles to kill tumor cells.

Systemic anti-tumor therapy

Targeted drugs are used to block tumor growth signaling pathways and inhibit tumor growth; or immunomodulators are used to activate and enhance the patient's own immune system to recognize and attack cancer cells, thereby releasing the inhibition of immune cells by tumor cells and exerting anti-tumor effects.

Next, let's see what insights Mr. Feng's treatment process, who has experienced two recurrences and suspicious lymph node metastasis, can offer you in today's highly developed technology.

Disease Overview

Overview of the illness

Mr. Feng, the patient, was found to have two lesions in his liver during a physical examination in March 2019: a 1.7*1.9cm lesion in the left liver and a 0.4*0.5cm lesion in the right liver, with a suspected malignant tumor in the left liver. On April 24, 2019, he underwent left lateral segmentectomy of the liver and cholecystectomy. Postoperative pathology revealed: (liver) hepatocellular carcinoma, moderately differentiated, Edmondson grade: III; tumor size 2X1.7X1.1cm, without involvement of the liver capsule; no cancer at the resection margin; surrounding liver tissue consistent with chronic viral hepatitis B G1, S3. Immunohistochemistry: cancer tissue: GPC-3(3+), Hepatocyte (3+), CD34 (diffusely distributed in microvessels), CK19 (-), Ki-67(+40%), p53 (2+), CK7 (1+). Liver tissue: HBsAg(2+), HBcAg (-). From April 2019 to 2020, he was treated with long-acting interferon and Zadaxin.

In 2020, a follow-up examination revealed an enlargement of the right liver lesion (specific details unknown). In November 2020, interventional ablation therapy was performed. On July 15, 2022, an upper abdominal MRI showed changes after resection of the liver lesion and interventional ablation, with a possible recurrence (an abnormal enhanced nodule measuring approximately 14mm*13mm was observed within the ablation lesion in the right lobe of the liver).

On July 22, 2022, a hepatic arteriography and embolization procedure were performed. On July 26, interventional ablation therapy was administered. On September 28, 2022, a PET-CT scan revealed postoperative changes in the left lobe of the liver after partial resection; a low-density lesion with high density in the right lobe of the liver, without metabolic activity, consistent with post-treatment changes in liver cancer, and clinical follow-up is recommended. A high-metabolic lymph node (SUVmax 9.44) measuring approximately 2.0cm x 1.2cm was found adjacent to the right external iliac artery, with a high likelihood of metastasis. On October 4, a pelvic CT scan showed: 1) an enlarged lymph node adjacent to the right external iliac artery, measuring approximately 1.9cm x 1.1cm, considered metastatic based on the patient's history; 2) prostatic calcification. On October 19, 2022, a lymph node resection was performed, and postoperative pathology revealed: frozen section examination (abdominal lymph nodes and surrounding tissues) showed two lymph nodes with reactive hyperplasia. Additional examination (perifascial fat around the inguinal lymph nodes) found four lymph nodes with reactive hyperplasia.

On May 26, 2023, the upper abdominal MR imaging revealed: 1. Postoperative changes following liver lesion resection and interventional ablation, with no clear signs of new or recurrent lesions; 2. Focal perfusion abnormalities in the liver, possibly indicating arteriovenous shunt, and a follow-up examination is recommended.

After experiencing two recurrences and suspicious lymph node metastasis, Mr. Feng and his family were deeply worried. Considering the high likelihood of another recurrence, they sought medical advice from various sources, hoping to find a treatment method that could control the tumor for a long time. Later, upon a friend's recommendation, Mr. Feng and his family learned about Professor Zhang Minghui's vNKT cell therapy technology at Tsinghua University School of Medicine and got in touch with us.

After reviewing Mr. Feng's medical records, Professor Zhang Minghui made the following second diagnosis and treatment suggestion for Lehe New Medicine:

1. Although the tumor was relatively small at the time of the patient's initial treatment, the lack of effective adjuvant therapy after surgery was the main reason for recurrence. Subsequently, the patient experienced two recurrences, both of which were treated with interventional combined radiofrequency ablation. This treatment method cannot completely eradicate the tumor, making recurrence inevitable. To consolidate the early treatment effects and control recurrence, more effective follow-up treatment measures are needed.

2. Current adjuvant therapy after surgery typically involves drug treatment, such as targeted therapy, chemotherapy (transcatheter arterial chemoembolization, TACE), and immunomodulatory therapy. These treatments can effectively kill and inhibit tumor cells in the short term, but drug resistance cannot be avoided, and long-term efficacy cannot be achieved. Additionally, they have significant side effects, which can damage the immune system, hematopoietic system, and organ function. Therefore, they are not ideal adjuvant therapy after surgery.

3. vNKT therapy can utilize powerful immune cells to eliminate residual or newly emerging tumor cells and reconstruct the immune microenvironment, with essentially no side effects. After completing surgical treatment, the tumor burden is reduced, making it the optimal intervention opportunity. vNKT therapy can effectively reduce the risk of recurrent and newly emerging tumors, making it highly suitable as the main treatment method for Mr. Feng's follow-up treatment.

# vNKT cell immunotherapy

NKT cells (Natural killer T cells), are a special T cell subset with both T cell receptor (TCR) and NK cell receptor on the cell surface. They possess important characteristics of both NK cells and T cells, with the dual ability to recognize tumor cells non-specifically and specifically, and can rapidly kill tumor cells. Among the NKT cell subsets, there is a larger and more potent special soldier, which was discovered by the experimental team led by Professor Zhang Minghui of Tsinghua University, namely vNKT (Variant Natural Killer T) cells.

The population of vNKT cells in the body is very small and they are not easily activated. However, once activated, they can effectively eliminate tumor cells that may remain undetected in the body. Additionally, research has found that vNKT cells exhibit a dual anti-tumor effect. Not only can they directly kill cancer cells, but they also modulate the immune microenvironment within tumor tissues, killing inhibitory immune cells such as MDSCs, breaking down tumor immune evasion, rebuilding the normal immune system, and further preventing recurrence and metastasis.

Experimental conditions: In the presence of vNKT cells, after 16 hours, nearly all B16 tumor cells were killed!
Professor Zhang introduced vNKT treatment technology and the treatment outcomes of previous cases in detail to Mr. Feng and his family, and provided detailed answers to Mr. Feng's questions. After thorough communication, he finally obtained the unanimous approval of Mr. Feng and his family. On August 1, 2023, vNKT cell therapy was started, with a regimen of one course per month. By November 1, 2024, 16 courses had been completed. Currently, the patient's condition is stable with no signs of recurrence or metastasis. The patient is in good spirits, with good appetite and sleep, and a good quality of life.

02

Changes in tumor markers
Tumor markers

From July 2016 to March 2023, AFP was reviewed to be within normal range.

03

Imaging changes
Imaging changes

Abdominal imaging: In July 2022, changes were observed after resection and interventional ablation of a liver lesion, with an abnormal enhancing nodule measuring 14mm*13mm in the ablation site of the right lobe of the liver, suggesting a possible recurrence. Follow-up examinations from September 2022 to July 2024 showed no clear new or recurrent lesions after resection and interventional ablation of the liver lesion, and a 3-month follow-up with further examination is recommended.

04

Conclusion and Comments
Conclusion and Commentary
Postoperative recurrence is the most concerning issue for all patients with malignant tumors who have undergone surgical treatment, and it is also the greatest obstacle to achieving tumor cure. All patients with tumors have varying degrees of recurrence risk after surgical treatment. According to current standard treatment methods, for postoperative recurrence, reoperation or local minimally invasive treatment is usually employed, combined with systemic pharmacotherapy such as chemotherapy, targeted therapy, and immunotherapy. These treatment methods can effectively kill and inhibit tumor cells in the short term, but drug resistance cannot be avoided, and long-term efficacy cannot be achieved. Moreover, they have significant side effects, which can damage the immune system, hematopoietic system, and organ function. Therefore, none of these methods are ideal postoperative adjuvant treatments.

vNKT therapy can utilize powerful immune cells to eliminate residual or newly emerging tumor cells, and can reconstruct the immune microenvironment with essentially no side effects. After completing surgical treatment, the tumor burden is reduced, which is the optimal intervention timing for vNKT cell therapy. After the second recurrence, Mr. Feng learned from the lessons of previous treatment failures and actively sought effective postoperative adjuvant therapy. After scientific analysis and comparison, he ultimately chose to undergo vNKT cell therapy. Since then, his condition has remained stable and achieved ideal therapeutic effects. Looking back on the entire treatment process, if Mr. Feng had used vNKT cell therapy immediately after his initial surgical treatment, it would have been highly likely to prevent subsequent recurrences. This shows that surgery combined with vNKT cell therapy is a novel tumor treatment modality that can effectively reduce the risk of recurrent and newly emerging tumors, providing patients with the possibility of achieving long-term tumor stability or even cure.

Zhang Minghui  Founder of Lehe New Medicine and Ph.D. in Immunology from Tsinghua University School of Medicine
Since the discovery of vNKT cells in 2002, Professor Zhang Minghui's research team has been engaged in research for over 20 years, accumulating treatment experience from over 700 cases of solid tumors, covering almost all common solid tumors. The research results fully demonstrate the great value of vNKT in the treatment of solid tumors.

It is suitable for postoperative patients with high malignant potential or at risk of recurrence; patients whose tumors have been largely controlled but not cured through conventional treatments such as chemotherapy, radiotherapy, and targeted therapy; and patients who continue to have high carcinogenic factors. If these patients do not receive effective follow-up treatment after traditional anti-tumor therapy, recurrence, metastasis, or reoccurrence of tumors will be highly probable. In this case, vNKT cell therapy is an ideal follow-up treatment method that can significantly improve the prognosis of patients.

References:
[1] BRAY F, FERLAY J, SOERJOMATARAM I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424 .
[2] GALLE P R, FORNER A, LLOVET J M, et al. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1):182-236.
[3] MARRERO JA, KULIK LM, SIRLIN CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma:2018 Practice Guidance by the American Association for the Study of Liver Diseases[J]. Hepatology, 2018, 68(2):723-750.
[4] VILLANUEVA A. Hepatocellular Carcinoma[J]. N Engl J Med, 2019, 380(15):1450-1462.

Written by: Liu Peng
Reviewed by: Qiao Jiacheng, Wang Ying, Gao Chen
Edited/typeset by Zhang Jiao

Welfare
Benefits for Liver Cancer Patients

Benefit 1
Clinical study recruitment for patients with advanced liver cancer
Primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of cancer-related deaths in China, posing a serious threat to the lives and health of our people. Due to the insidious onset of liver cancer, less than 30% of patients are suitable for radical treatment at the time of initial diagnosis. Systemic anti-tumor therapy plays a crucial role in the treatment of advanced liver cancer. Immunotherapy, represented by targeted and immune checkpoint inhibitors, plays a significant role in the treatment of advanced liver cancer. However, when patients progress after second-line treatment, there is a lack of corresponding guidelines or consensus for medication or treatment guidance, leading to difficulties for clinicians and patients in choosing appropriate medications.


Immunotherapy for malignant tumors, besides immune checkpoint inhibitors, also includes active immunotherapy that activates the body's own immune function. Among them, NKT cells have garnered significant attention due to their dual characteristics of NK cells and T cells. Activated vNKT cells (variant NKT) can not only directly kill tumor cells but also target myeloid-derived suppressor cells in the tumor microenvironment (TME), thus potentially offering better tumor treatment outcomes.


Immunotherapy targeting vNKT immune cells for hepatocellular carcinoma brings new hope to patients with advanced liver cancer who have progressed after second-line treatment. To this end, Professor Zhang Minghui's Lehe New Medical Research Team at Tsinghua University and Shanghai East Hepatobiliary Surgery Hospital have jointly launched a clinical research recruitment program for patients with advanced hepatocellular carcinoma, so that more patients who meet the clinical research criteria can benefit!

How to participate?

If you are a patient with liver cancer or a family member, you can contact our assistant to provide your patient's medical records. After a one-on-one assessment of the condition by a professional medical team, you can apply to participate in clinical research. For details, please scan the QR code to inquire

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Communicate with Professor Zhang Minghui's team

Benefit 2
Liver Cancer Patient Exchange Group
Professor Zhang Minghui of Tsinghua University has always harbored the great aspiration of "a world without disease" and is committed to providing a patient-centered platform for patients to exchange and help each other. Whether you have just been diagnosed, are troubled by side effects, don't know how to choose a treatment plan, want to share experiences and insights, or simply pour out your heart, you are welcome here!

In the group, there are professional experts giving lectures and enthusiastic group members for exchanges. Moreover, you have the opportunity to apply for clinical research enrollment. Join the group and enjoy a happy and healthy life!

Want to know more about the comprehensive treatmentsuggestions for liver cancer
Welcome to the Lehe New Medical Liver Cancer Exchange Group

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