Percutaneous Ablation of Hepatic Tumors at the Hepatocaval Confluence Using Irreversible Electroporation: A Preliminary Study
, Wei Huang 1,†, Zhiyuan Wu 1, Yong Wang 2, Qingbing Wang 1, Ziyin Wang 1, Qin Liu 1, Jingjing Liu 1, Shenjie Wang 1, Xiaoyi Ding 1,* and Zhongmin Wang 1,*
Round 1
Reviewer 1 Report
Indeed, hepatocaval fusion tumors are difficult to treat surgically or ablatively. In this work, the authors conducted a retrospective longitudinal study of patients in whom thermal ablation is contraindicated and who underwent computed tomography-guided IRE for liver tumors in the area of ​​the hepatocaval fusion. Complete ablation was achieved in all cases. Local and distant recurrence was observed in 4.8% (1/21) and 42.6% (9/21) of resected tumors, respectively. Progression-free survival in patients with relapse was 121 (range 25–566) days. Four (19.0%) patients died at the end of the follow-up period with a median overall survival of 451.5 (range 25–716) days. I believe that the results of this study should be published and will be of interest to readers. Questions to the authors: 1) Since the study includes rather rare cases, the number of patients is small. I would recommend authors to submit their results as preliminary. 2) How do recurrences correlate with tumor features and characteristics, type of treatment, etc.? This applies to both local and distant recurrence.
Author Response
Dear reviewer,
Thank you for your pertinent rational comments on this article.
Point 1: Since the study includes rather rare cases, the number of patients is small. I would recommend authors to submit their results as preliminary.
Response 1: As you mentioned, the number of cases included in this study is small. This is because this study is limited to the specificity of hepatic tumors at the hepatocaval confluence.
1. Low incidence of hepatic tumors at the hepatocaval confluence.
The distribution of liver tumors is closely related to the anatomical volume, and liver tumors mainly occur in the right lobe of liver. Both the primary tumor and the metastases are mainly located in the right lobe of the liver. Specifically, primary tumors and metastases tend to occur in different liver segments. Matteo Renzulli analyzed segmental distribution of hepatocellular carcinoma in cirrhotic Livers, with 322 HCC nodules diagnosed in 217 cirrhotic patients; HCC was most common in segment VIII (n = 88, 27.4%) [1]. Moreover, in a statistical analysis of 985 patients from Cengiz Kadiyoran, the right lobe posterior segment (segment VI) is the main target of metastases, which is not close to hepatocaval confluence [2]. The hepatocaval confluence region involves parts of four liver segments, and there is no report on the incidence of related liver tumors. However, if the incidence is based on the regional volume of the total liver volume, the incidence of tumors at the hepatocaval confluence is relatively low.
2. Determination of treatment options from patients and doctors.
The treatment varies according to the number size and location of the liver tumors. With these parameters, radiofrequency ablation (RFA), segmentectomy, lobectomy, transarterial-chemoembolisation (TACE), immunotherapy, or chemotherapy treatment options would be used according to the doctor's opinion and the patient's wishes [3]. There is currently no guideline or expert consensus for liver tumors at the hepatocaval confluence. Disease-based treatment guidelines include interventional therapy as one of the treatment methods for surgically unresectable liver tumors. When the tumor occurs at the second porta hepatis, the patient's treatment plan is diverse affected by the diversity of doctor's advice based on condition and the patient's wishes. In general, the number of liver tumors at hepatocaval confluence treated with IRE is relatively small, which also reflects the significance of this study.
Therefore, based on your suggestion, we resubmitted this study as preliminary findings and have revised the title to remind readers
Point 2: How do recurrences correlate with tumor features and characteristics, type of treatment, etc.? This applies to both local and distant recurrence.
Response 2: Indeed, recurrence may be closely related to tumor characteristics and treatment methods. To this end, we further calculated the recurrence rate of related treatment modalities, including preoperative and postoperative. Table 1 and Table 5 have been adjusted and supplemented. Additionally, we performed a statistical analysis of whether tumor-to-vascular distance was associated with recurrence rates, which was described on line 234-237.
References
- Renzulli, M.; Brandi, N.; Pecorelli, A.; Pastore, L.V.; Granito, A.; Martinese, G.; Tovoli, F.; Simonetti, M.; Dajti, E.; Colecchia, A.; et al. Segmental Distribution of Hepatocellular Carcinoma in Cirrhotic Livers. Diagnostics (Basel, Switzerland) 2022, 12, doi:10.3390/diagnostics12040834.
- Kadiyoran, C.; Cizmecioglu, H.A.; Cure, E.; Yildirim, M.A.; Yilmaz, P.D. Liver metastasis in colorectal cancer: evaluation of segmental distribution. Przeglad gastroenterologiczny 2019, 14, 188-192, doi:10.5114/pg.2019.88168.
- Lee, H.Y.; Chung, J.W.; Lee, J.M.; Yoon, C.J.; Lee, W.; Jae, H.J.; Yin, Y.H.; Kang, S.G.; Park, J.H. A new and simple practical plane dividing hepatic segment 2 and 3 of the liver: evaluation of its validity. Korean journal of radiology 2007, 8, 302-310, doi:10.3348/kjr.2007.8.4.302.
Reviewer 2 Report
Main Comment:
This manuscript deals with the use of irreversible electroporation for percutaneous ablation of tumors at the hepatocaval confluence. The evaluation presented by the authors has the drawbacks of a retrospective study design and comprises a small number of patients with considerable heterogeneity. Several questions (longer follow-up, the problem of potential needle tract seeding, the impact of combined treatments, etc.) remain open. More research will be needed for sound evidence.
Specific Comments/Suggestions:
Abstract, lines 15-17: "A retrospective longitudinal study on patients ineligible for thermal ablation and underwent computed tomography-guided IRE for hepatic tumors at the hepatocaval confluence was conducted" -> … on patients ineligible for thermal ablation who underwent computed tomography-guided IRE…
Introduction, lines 51-54: "First, the heat sink effect of adjacent large vessels is prominent, and vessels > 5 mm are prone to incomplete tumor ablation or local tumor progression3. Second, due to deep tumor location and complex anatomical structures, the procedure of puncturing and ablating may also cause damage [8]" – is "progression3" meant to be a citation? -> progression [3]?
Introduction, lines 56-58: "Unlike heat-based ablation that induces cell death through coagulation necrosis, IRE creates permanent nanoscale perforations on tumor cells by releasing high-pressure electric pulses, disrupting intracellular homeostatic, and causing programmed cell death [9]" -> … disrupting intracellular homeostasis…
Introduction, lines 65-67: "Although IRE is a viable treatment for hepatic tumors at the hepatocaval confluence, its feasibility, complication, and prognosis have not yet been confirmed in clinical setting" -> …its feasibility, complications…
Materials and Methods, line 73: "Patient" -> Patients.
Materials and Methods, lines 84-86: "All procedures were performed using the NanoKnife (AngioDynamics, Latham, New York, USA) system by an experienced team comprising of interventional radiologist, anesthetist, itinerant nurse, and trained machine operator" -> … by an experienced team comprising an interventional radiologist, an anesthetist, an itinerant nurse, and a trained machine operator.
Materials and Methods, lines 95-97: "Electrode distribution were sited to build an ablation zone encompassing the target lesion and rim of surrounding tissue" -> ...was sited…
Materials and Methods, lines 103-105: "Immediately after IRE procedure, contrast-enhanced CT of the upper abdomen was performed to assess whether ablation was complete and procedure-related complications (e.g., hemoperitoneum, pneumothorax, pleural effusion, and biliary obstruction)" -> ...contrast-enhanced CT of the upper abdomen was performed to assess whether ablation was complete and to detect procedure-related complications (e.g., hemoperitoneum, pneumothorax, pleural effusion, and biliary obstruction).
Materials and Methods, lines 112-113: "The lesions adjacent to the ablation site was termed local recurrence, and those distant from the ablation site was termed distant recurrence" -> The lesions adjacent to the ablation site were termed local recurrence, and those distant from the ablation site were termed distant recurrence.
Results, line 132/133: "Median age was 58 years old (range, 41–83 years)" -> Median age was 58 years (range, 41–83 years).
Results, line 157: "2 (9.5%) in Segments 4a" -> ... in Segment 4a.
Results, lines 177-179: "When complete ablation cannot be achieved during a single ablation session, pull-back technique (n = 14; 66.7%) or electrode replacement (n =6; 28.6%) was then performed" -> When complete ablation could not be achieved during a single ablation session, pull-back technique (n = 14; 66.7%) or electrode replacement (n = 6; 28.6%) was performed.
Discussion, line 226/227: "…as low as 10–25% [13] In addition…" -> …as low as 10–25% [13]. In addition…
Discussion, line 247: "Conor et al." -> O'Neill et al. (see reference 17).
Discussion, lines 247-249: "…on 481 patients receiving IRE, only 1.2% (5/422) of them undergoing cardiac synchronization experienced arrhythmias compared with 22.0% (13/59) of the unsynchronized experienced it [17]" -> …on 481 patients receiving IRE, only 1.2% (5/422) of those undergoing cardiac synchronization experienced arrhythmias compared with 22.0% (13/59) of those without synchronization [17].
Discussion, lines 257/258: "The reason for a higher incidence in this current study is thought to be the lesions closer to the diaphragm and pleura" -> The reason for a higher incidence in this current study is thought to be the closeness of the lesions to diaphragm and pleura.
Discussion, line 268: "Sebastian et al." -> Mafeld et al. (see reference 21).
Discussion, line 273: "Russell et al." -> Langan et al. (see reference 23).
Discussion, line 282: "Mohammed et al." -> Alnaggar et al. (see reference 27).
Discussion, line 290: "The changes in the lesions was monitored by contrast-enhanced CT or MRI" -> The changes in the lesions were monitored by contrast-enhanced CT or MRI.
Discussion, line 293/294: "Veeru et al." -> Kasivisvanathan V et al. (see reference 30).
Discussion, line 296-298: "Similar results were illustrated in a study on perivascular hepatic malignant tumors treated with IRE, where the median ablation zone area decreased to 9 cm2, 2.3 cm2, and 2.3 cm2 at 1, 3, and 6 months [23]" – from which initial size? The numbers given here could not be verified in reference 23.
Reference list: Revision is required in order to comply with the "Instructions for Authors".
Author Response
Dear reviewer,
Thank you for your pertinent rational comments on this article.
Point 1: The evaluation presented by the authors has the drawbacks of a retrospective study design and comprises a small number of patients with considerable heterogeneity.
Response 1: As you mentioned, the number of cases included in this study is small. This is because this study is limited to the specificity of hepatic tumors at the hepatocaval confluence.
1. Low incidence of hepatic tumors at the hepatocaval confluence.
The distribution of liver tumors is closely related to the anatomical volume, and liver tumors mainly occur in the right lobe of liver. Both the primary tumor and the metastases are mainly located in the right lobe of the liver. Specifically, primary tumors and metastases tend to occur in different liver segments. Matteo Renzulli analyzed segmental distribution of hepatocellular carcinoma in cirrhotic Livers, with 322 HCC nodules diagnosed in 217 cirrhotic patients; HCC was most common in segment VIII (n = 88, 27.4%) [1]. Moreover, in a statistical analysis of 985 patients from Cengiz Kadiyoran, the right lobe posterior segment (segment VI) is the main target of metastases, which is not close to hepatocaval confluence [2]. The hepatocaval confluence region involves parts of four liver segments, and there is no report on the incidence of related liver tumors. However, if the incidence is based on the regional volume of the total liver volume, the incidence of tumors at the hepatocaval confluence is relatively low.
2. Determination of treatment options from patients and doctors.
The treatment varies according to the number size and location of the liver tumors. With these parameters, radiofrequency ablation (RFA), segmentectomy, lobectomy, transarterial-chemoembolisation (TACE), immunotherapy, or chemotherapy treatment options would be used according to the doctor's opinion and the patient's wishes [3]. There is currently no guideline or expert consensus for liver tumors at the hepatocaval confluence. Disease-based treatment guidelines include interventional therapy as one of the treatment methods for surgically unresectable liver tumors. When the tumor occurs at the second porta hepatis, the patient's treatment plan is diverse affected by the diversity of doctor's advice based on condition and the patient's wishes. In general, the number of liver tumors at hepatocaval confluence treated with IRE is relatively small, which also reflects the significance of this study.
Cases with more samples require longer retrospective studies and/or involvement of more centers. Therefore, based on available research data, we resubmitted this study as preliminary study and have revised the title to remind readers.
Point 2: Several questions (longer follow-up, the problem of potential needle tract seeding, the impact of combined treatments, etc.) remain open.
Response 2: Indeed, recurrence may be closely related to tumor characteristics and treatment methods. To this end, we further calculated the recurrence rate of related treatment modalities, including preoperative and postoperative. Table 1 and Table 5 have been adjusted and supplemented. Additionally, we performed a statistical analysis of whether tumor-to-vascular distance was associated with recurrence rates, which was described on line 234-237.
Point 3: Some statement and citation errors.
Response 3: We have corrected the formatting and grammatical errors you pointed out, and reinserted the article citations via endnote software in "MDPI.ens" style following "Instructions for Authors".
Point 4: Discussion, line 363-365: "Similar results were illustrated in a study on perivascular hepatic malignant tumors treated with IRE, where the median ablation zone area decreased to 9 cm2, 2.3 cm2, and 2.3 cm2 at 1, 3, and 6 months (33)".
Response 4: We rechecked the citation. The relevant data can be found in Table 4 of citation 33 "Ablation of perivascular hepatic malignant tumors with irreversible electroporation".
References
- Renzulli, M.; Brandi, N.; Pecorelli, A.; Pastore, L.V.; Granito, A.; Martinese, G.; Tovoli, F.; Simonetti, M.; Dajti, E.; Colecchia, A.; et al. Segmental Distribution of Hepatocellular Carcinoma in Cirrhotic Livers. Diagnostics (Basel, Switzerland) 2022, 12, doi:10.3390/diagnostics12040834.
- Kadiyoran, C.; Cizmecioglu, H.A.; Cure, E.; Yildirim, M.A.; Yilmaz, P.D. Liver metastasis in colorectal cancer: evaluation of segmental distribution. Przeglad gastroenterologiczny 2019, 14, 188-192, doi:10.5114/pg.2019.88168.
- Lee, H.Y.; Chung, J.W.; Lee, J.M.; Yoon, C.J.; Lee, W.; Jae, H.J.; Yin, Y.H.; Kang, S.G.; Park, J.H. A new and simple practical plane dividing hepatic segment 2 and 3 of the liver: evaluation of its validity. Korean journal of radiology 2007, 8, 302-310, doi:10.3348/kjr.2007.8.4.302.
Thank you again for your valuable comments and suggestions.
