Non-Invasive Treatment of Liver Tumors: The Revolutionary Role of Histotripsy

Liver tumors, whether benign or malignant, have long been a significant health concern. Traditional treatments, while effective, often involve invasive surgical procedures that come with inherent risks and complications. For many patients, especially those with small, numerous, or strategically located tumors, surgery might not be a viable option. However with Histotripsy, a groundbreaking procedure that promises a non-invasive alternative with remarkable potential, effective non-invasive treatment liver cancer is now possible.

Histotripsy is a novel medical procedure that harnesses the power of ultrasound waves to mechanically disintegrate tissue structures. Unlike other treatments that depend on heat or radiation, histotripsy utilizes the sheer force of sound waves. These waves are meticulously focused on the target tissue, leading to its fragmentation without harming the surrounding healthy tissue. The precision and non-invasive nature of histotripsy make it a beacon of hope for liver tumor patients.

A Closer Look at Evidence

Research has demonstrated the efficacy of histotripsy in creating safe and effective ablations in the in vivo human-scale porcine normal liver. In various studies, target liver volumes ranging from 12–60 ml were completely ablated in durations spanning 20–75 min. The results were consistent and promising: within the ablated region, there was uniform tissue disruption with no viable cells remaining. Impressively, major vessels and bile ducts remained intact.

The realm of medical treatments has always been complemented by the power of visual evidence, providing clinicians, researchers, and patients with tangible proof of a procedure’s effectiveness. Magnetic Resonance Imaging (MRI) stands at the forefront of this visual exploration. The high-resolution images produced by MRI scanners offer a detailed look into the internal structures of the liver, both before and after histotripsy treatment. Specifically, axial T2-weighted MR images have been invaluable (Figure 1). These images vividly depict the ablation volume, which is the targeted area that underwent histotripsy. The clarity and precision of these images allow medical professionals to ascertain the exact boundaries of the treated area, ensuring that the tumor cells have been effectively disrupted while leaving the surrounding healthy liver tissues untouched.

Complementing the MRI scans are gross morphological examinations. These examinations, often conducted post-procedure, provide a hands-on, macroscopic view of the liver. They reveal a consistent pattern of tissue disruption within the ablation zone, characterized by a lack of viable hepatocytes, which are the primary cells of the liver. This uniformity in tissue disruption is a testament to histotripsy’s precision, ensuring that the treatment is both thorough and targeted.

Reproduced from
Figure 1: (A–D) Histotripsy treatment in the in vivo porcine liver. Axial T2-weighted MR images (A) and gross morphology (B) show the spherical ablation volume. (C) H&E slide of (100X) of the center of the ablation zone demonstrates no viable hepatocytes. (D) H&E slide (100X) of the periphery of the ablation shows viable liver (L), necrotic liver (N), and a thin zone of transition (Z). (E–G) MR images of partial histotripsy treatment in a rodent HCC model. (E) The appearance of the original untreated tumor on T2-weighted MRI was hyperintense (yellow arrow). (F) Post histotripsy, the ablation zone demonstrates T2 hypointense signal (red dashed lines). (G) At 12 weeks, only a ∼5 mm non-tumoral fibrous tissue zone is detectable on MRI at the original tumor site, indicating near-complete resolution of the ablation zone and tumor. (H–I) Histotripsy induced immune response and abscopal effect (reproduction based on images from ref [Citation]. (H) FACS analysis of histotripsy-ablated (HT ablated) and contralateral non-ablated tumors (HT abscopal) identified comparable levels of intratumoral CD8+ T cell infiltration that is significantly higher than the untreated control tumors. (I) At gross examination, pulmonary metastases were reduced in mice treated with histotripsy compared to untreated controls.

Furthermore, the visual evidence extends beyond just the immediate aftermath of the procedure. MR images from rodent Hepatocellular Carcinoma (HCC) models, a common type of liver cancer, provide insights into the longer-term effects of histotripsy. Initial scans of these models show tumors with a hyperintense signal on T2-weighted MRI, indicating active and aggressive tumor growth. However, post-histotripsy images paint a different picture. The previously hyperintense tumors now display a T2 hypointense signal within the ablation zone, signifying successful disruption of the tumor cells. Even more promising are follow-up scans taken 12 weeks after the procedure. These images often reveal a near-total disappearance of the tumor, replaced by a small fibrous tissue zone. This transformation underscores histotripsy’s potential not just as a treatment method but as a possible path to long-term recovery.

The visual evidence supporting histotripsy’s effectiveness is both compelling and comprehensive. From high-resolution MRI scans to hands-on morphological examinations, each piece of evidence builds a case for histotripsy as a revolutionary, non-invasive treatment for liver tumors.

What are the benefits of Histotripsy for Liver Tumor Treatment?

  1. Non-Invasive Approach: One of the most significant advantages of histotripsy is its non-invasive nature. Patients do not require incisions, which means there’s a reduced risk of infections, shorter recovery times, and minimal scarring.
  2. Precision Targeting: Histotripsy offers unparalleled precision. The ultrasound waves can be directed to target only the tumor cells, ensuring that the surrounding healthy liver tissue remains unharmed. This is especially crucial for the liver, where preserving as much healthy tissue as possible is vital for its regenerative capabilities.
  3. Suitable for Multiple Small Tumors: Patients with multiple small tumors scattered throughout the liver often find surgical options limited. Histotripsy can target each of these tumors individually, offering a comprehensive treatment solution.
  4. Reduced Side Effects: Since histotripsy doesn’t rely on radiation or thermal energy, patients experience fewer side effects compared to other treatments like radiotherapy or thermal ablation.

The Immune Response of Histotripsy

Another fascinating aspect of histotripsy is its potential to induce an immune response. FACS analysis of histotripsy-ablated tumors identified significant levels of intratumoral CD8+ T cell infiltration, much higher than untreated control tumors. This suggests that histotripsy might play a role in boosting the body’s natural defenses against cancer cells. Additionally, there was a noticeable reduction in pulmonary metastases in mice treated with histotripsy compared to untreated controls.

Given that bones, especially ribs, are highly reflective and absorptive for ultrasound propagation, the feasibility and safety of histotripsy through ribs were meticulously studied. The results were reassuring. Ablation zones created through full ribcage coverage were comparable to those with only overlying soft tissue. The temperature increase to ribs was minimal, ensuring no thermal damage to the ribs or surrounding tissue.

However, it’s worth noting that in one paper by Smolock et al., body wall damage was reported. This was likely due to pre-focal cavitation on the ribs. But subsequent studies addressed this by adjusting the focal pressure and duty cycle, effectively eliminating such damage. In some cases, transient thrombosis in portal and hepatic veins was observed within the treatment zone, akin to outcomes from radiofrequency and microwave ablation.

The long-term response to liver treatment by histotripsy has also been studied. In normal rodent models, the acellular homogenate generated by histotripsy was absorbed within a month, leaving only a minuscule fibrous region. In tumor treatment studies, tumors were completely absorbed within 7–10 weeks post-histotripsy, with no evidence of residual tumor after three months.

In conclusion, Histotripsy is undeniably a game-changer in the realm of liver tumor treatments. Its non-invasive nature, combined with its precision and efficacy, makes it a promising alternative to traditional surgical interventions. As research continues and technology advances, histotripsy could very well become the gold standard for treating not just liver tumors but a plethora of other medical conditions. For patients and medical professionals alike, it heralds a future of safer, more effective, and less invasive treatment options.


Reviewed By : Dr. Aviral Vatsa

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