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Keywords = post hepatectomy liver failure

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21 pages, 599 KiB  
Review
Radiomics Beyond Radiology: Literature Review on Prediction of Future Liver Remnant Volume and Function Before Hepatic Surgery
by Fabrizio Urraro, Giulia Pacella, Nicoletta Giordano, Salvatore Spiezia, Giovanni Balestrucci, Corrado Caiazzo, Claudio Russo, Salvatore Cappabianca and Gianluca Costa
J. Clin. Med. 2025, 14(15), 5326; https://doi.org/10.3390/jcm14155326 - 28 Jul 2025
Viewed by 237
Abstract
Background: Post-hepatectomy liver failure (PHLF) is the most worrisome complication after a major hepatectomy and is the leading cause of postoperative mortality. The most important predictor of PHLF is the future liver remnant (FLR), the volume of the liver that will remain after [...] Read more.
Background: Post-hepatectomy liver failure (PHLF) is the most worrisome complication after a major hepatectomy and is the leading cause of postoperative mortality. The most important predictor of PHLF is the future liver remnant (FLR), the volume of the liver that will remain after the hepatectomy, representing a major concern for hepatobiliary surgeons, radiologists, and patients. Therefore, an accurate preoperative assessment of the FLR and the prediction of PHLF are crucial to minimize risks and enhance patient outcomes. Recent radiomics and deep learning models show potential in predicting PHLF and the FLR by integrating imaging and clinical data. However, most studies lack external validation and methodological homogeneity and rely on small, single-center cohorts. This review outlines current CT-based approaches for surgical risk stratification and key limitations hindering clinical translation. Methods: A literature analysis was performed on the PubMed Dataset. We reviewed original articles using the subsequent keywords: [(Artificial intelligence OR radiomics OR machine learning OR deep learning OR neural network OR texture analysis) AND liver resection AND CT]. Results: Of 153 pertinent papers found, we underlined papers about the prediction of PHLF and about the FLR. Models were built according to machine learning (ML) and deep learning (DL) automatic algorithms. Conclusions: Radiomics models seem reliable and applicable to clinical practice in the preoperative prediction of PHLF and the FLR in patients undergoing major liver surgery. Further studies are required to achieve larger validation cohorts. Full article
(This article belongs to the Special Issue Advances in Gastroenterological Surgery)
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15 pages, 1275 KiB  
Systematic Review
A Systematic Review of Closed-Incision Negative-Pressure Wound Therapy for Hepato-Pancreato-Biliary Surgery: Updated Evidence, Context, and Clinical Implications
by Catalin Vladut Ionut Feier, Vasile Gaborean, Ionut Flaviu Faur, Razvan Constantin Vonica, Alaviana Monique Faur, Vladut Iosif Rus, Beniamin Sorin Dragan and Calin Muntean
J. Clin. Med. 2025, 14(15), 5191; https://doi.org/10.3390/jcm14155191 - 22 Jul 2025
Viewed by 321
Abstract
Background and Objectives: Postoperative pancreatic fistula and post-hepatectomy liver failure remain significant complications after HPB surgery; however, superficial surgical site infection (SSI) is the most frequent wound-related complication. Closed-incision negative-pressure wound therapy (ciNPWT) has been proposed to reduce superficial contamination, yet no [...] Read more.
Background and Objectives: Postoperative pancreatic fistula and post-hepatectomy liver failure remain significant complications after HPB surgery; however, superficial surgical site infection (SSI) is the most frequent wound-related complication. Closed-incision negative-pressure wound therapy (ciNPWT) has been proposed to reduce superficial contamination, yet no liver-focused quantitative synthesis exists. We aimed to evaluate the effectiveness and safety of prophylactic ciNPWT after hepatopancreatobiliary (HPB) surgery. Methods: MEDLINE, Embase, and PubMed were searched from inception to 30 April 2025. Randomized and comparative observational studies that compared ciNPWT with conventional dressings after elective liver transplantation, hepatectomy, pancreatoduodenectomy, and liver resections were eligible. Two reviewers independently screened, extracted data, and assessed risk of bias (RoB-2/ROBINS-I). A random-effects Mantel–Haenszel model generated pooled risk ratios (RRs) for superficial SSI; secondary outcomes were reported descriptively. Results: Twelve studies (seven RCTs, five cohorts) encompassing 15,212 patients (3561 ciNPWT; 11,651 control) met the inclusion criteria. Device application lasted three to seven days in all trials. The pooled analysis demonstrated a 29% relative reduction in superficial SSI with ciNPWT (RR 0.71, 95% CI 0.63–0.79; p < 0.001) with negligible heterogeneity (I2 0%). Absolute risk reduction ranged from 0% to 13%, correlating positively with the baseline control-group SSI rate. Deep/organ-space SSI (RR 0.93, 95% CI 0.79–1.09) and 90-day mortality (RR 0.94, 95% CI 0.69–1.28) were unaffected. Seven studies documented a 1- to 3-day shorter median length of stay; only two reached statistical significance. Device-related adverse events were rare (one seroma, no skin necrosis). Conclusions: Prophylactic ciNPWT safely reduces superficial SSI after high-risk HPB surgery, with the greatest absolute benefit when baseline SSI risk exceeds ≈10%. Its influence on deep infection and mortality is negligible. Full article
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19 pages, 6583 KiB  
Case Report
New Horizons: The Evolution of Nuclear Medicine in the Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors—A Case Report
by Annamária Bakos, László Libor, Béla Vasas, Kristóf Apró, Gábor Sipka, László Pávics, Zsuzsanna Valkusz, Anikó Maráz and Zsuzsanna Besenyi
J. Clin. Med. 2025, 14(13), 4432; https://doi.org/10.3390/jcm14134432 - 22 Jun 2025
Viewed by 523
Abstract
Background: Pancreatic neuroendocrine tumors (PanNETs) are relatively rare neoplasms with heterogeneous behavior, ranging from indolent to aggressive disease. The evolution of nuclear medicine has allowed the development of an efficient and advanced toolkit for the diagnosis and treatment of PanNETs. Case: [...] Read more.
Background: Pancreatic neuroendocrine tumors (PanNETs) are relatively rare neoplasms with heterogeneous behavior, ranging from indolent to aggressive disease. The evolution of nuclear medicine has allowed the development of an efficient and advanced toolkit for the diagnosis and treatment of PanNETs. Case: A 45-year-old woman was diagnosed with a grade 1 PanNET and multiple liver metastases. She underwent distal pancreatectomy with splenectomy, extended liver resection, and radiofrequency ablation (RFA). Surgical planning was guided by [99mTc]Tc-EDDA/HYNIC-TOC SPECT/CT (single-photon emission computed tomography/computed tomography) and preoperative [99mTc]Tc-mebrofenin-based functional liver volumetry. Functional liver volumetry based on dynamic [99mTc]Tc-mebrofenin SPECT/CT facilitated precise surgical planning and reliable assessment of the efficacy of parenchymal modulation, thereby aiding in the prevention of post-hepatectomy liver failure. Liver fibrosis was non-invasively evaluated using two-dimensional shear wave elastography (2D-SWE). Tumor progression was monitored using somatostatin receptor scintigraphy, chromogranin A, and contrast-enhanced CT. Recurrent disease was treated with somatostatin analogues (SSAs) and [177Lu]Lu-DOTA-TATE peptide receptor radionuclide therapy (PRRT). Despite progression to grade 3 disease (Ki-67 from 1% to 30%), the patient remains alive 53 months post-diagnosis, in complete remission, with an ECOG (Eastern Cooperative Oncology Group) status of 0. Conclusions: Functional imaging played a pivotal role in guiding therapeutic decisions throughout the disease course. This case not only underscores the clinical utility of advanced nuclear imaging but also illustrates the dynamic nature of pancreatic neuroendocrine tumors. The transition from low-grade to high-grade disease highlights the need for further studies on tumor progression mechanisms and the potential role of adjuvant therapies in managing PanNETs. Full article
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15 pages, 2444 KiB  
Article
Optical Coherence Tomography Angiography, Elastography, and Attenuation Imaging for Evaluation of Liver Regeneration
by Svetlana Rodimova, Ekaterina Gubarkova, Nikolai Bobrov, Ilya Shchechkin, Vera Kozlova, Natalia Zolotova, Arseniy Potapov, Elena Kiseleva, Grigory Gelikonov, Natalia Gladkova, Vladimir Zagainov, Elena Zagaynova and Daria Kuznetsova
Diagnostics 2025, 15(8), 977; https://doi.org/10.3390/diagnostics15080977 - 11 Apr 2025
Viewed by 694
Abstract
Background/Objectives: As a result of metabolic changes and the disruption of tissue architecture and microcirculation, the regenerative potential of the liver decreases with violations at both micro and macro levels. The development of intraoperative approaches for assessing its regenerative potential is important for [...] Read more.
Background/Objectives: As a result of metabolic changes and the disruption of tissue architecture and microcirculation, the regenerative potential of the liver decreases with violations at both micro and macro levels. The development of intraoperative approaches for assessing its regenerative potential is important for reducing the risk of the occurrence of post-resection liver failure. In this study, we used multimodal optical coherence tomography (MM OCT), a combination of three optical coherence tomography modalities—OCT–angiography (OCTA), attenuation coefficient mapping, and OCT–elastography (OCE) to provide real-time three-dimensional and label-free assessment of changes in microcirculation, and in the structure and stiffness of the liver during regeneration. Methods: In our study, the regeneration of a healthy liver was induced by 70% partial hepatectomy. Monitoring of changes was carried out on the 0 (normal liver), 3rd and 7th day of regeneration using modalities of MM OCT. OCT offers the benefits of higher resolution and specificity compared with other clinical imaging modalities, and can be used, even intraoperatively. Results: By the 3rd day of liver regeneration, a decreased density of all observable vessels, together with increased values of the liver tissue’s attenuation coefficient and stiffness, was revealed compared to their initial state. However, by the 7th day, the studied parameters tended to return to their normal values, except that the density of large-caliber vessels continued to increase further. Histological and biochemical blood analysis methods were used to verify the MM OCT data. Conclusions: Such data are a first step towards further investigation of liver regeneration in pathology, and, taken in perspective, this should serve as a basis for predictive intraoperative assessment of the regenerative potential of the liver in a clinical setting. Full article
(This article belongs to the Section Biomedical Optics)
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12 pages, 1461 KiB  
Article
Predictors of Post-Hepatectomy Liver Failure in Klatskin Tumors: The Role of Preoperative Glucose, Future Liver Remnant to Spleen Ratio, and Early Bilirubin Monitoring
by Suyeon Kim, Hyung June Ku, Hyung Hwan Moon, Sang Hwa Song, Young Il Choi, Dong Hoon Shin, Yang Seok Koh, Namkee Oh, Jinsoo Rhu, Garam Lee, Won Jong Yang, Junho Song, Chol Min Kang, Seoyeong Ku and Amy Choi
Diagnostics 2024, 14(23), 2716; https://doi.org/10.3390/diagnostics14232716 - 2 Dec 2024
Cited by 1 | Viewed by 1600
Abstract
Background: Post-hepatectomy liver failure (PHLF) is a serious complication following hepatic resection for Klatskin tumors, significantly affecting patient prognosis. Identifying reliable preoperative and early postoperative predictors of PHLF can help optimize patient outcomes and guide surgical planning. Method: We conducted a [...] Read more.
Background: Post-hepatectomy liver failure (PHLF) is a serious complication following hepatic resection for Klatskin tumors, significantly affecting patient prognosis. Identifying reliable preoperative and early postoperative predictors of PHLF can help optimize patient outcomes and guide surgical planning. Method: We conducted a retrospective review of 34 patients who underwent hemi-hepatectomy for extrahepatic cholangiocarcinoma at Kosin University Gospel Hospital between April 2019 and April 2024, and at Chonnam National University Hwasun Hospital between September 2017 and April 2024. Demographics, laboratory data, and volumetric measurements including spleen volume, were analyzed to assess their roles in predicting PHLF. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive value of these factors. Results: Elevated preoperative glucose levels and reduced future liver remnant to spleen ratio (FLR/SV) were significantly associated with an increased risk of PHLF. Additionally, elevated postoperative day 1 total bilirubin (POD 1 TB) was identified as a key postoperative predictor of PHLF. Multivariable analysis confirmed the significance of these factors, with FLR/SV, preoperative glucose, and POD 1 TB demonstrating good discriminative ability in ROC analysis, with AUC values of 0.779, 0.782, and 0.786 respectively. Conclusion: Preoperative glucose control, evaluation of FLR/SV, and early postoperative monitoring of TB are useful for improving outcomes in patients undergoing major hepatectomy for Klatskin tumors. Full article
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13 pages, 5958 KiB  
Article
A Novel Bile Duct-Saving Portal Ligation Technique for Subtotal Hepatectomy Survival Operations in Rats
by Kush Savsani, Anjelica Alfonso, Ester Jo, Andrew Park and Seung Duk Lee
Livers 2024, 4(4), 521-533; https://doi.org/10.3390/livers4040037 - 15 Oct 2024
Viewed by 1638
Abstract
Background: Creating a model for acute liver failure in animal models is essential for research on liver regeneration and cancer. Current surgical techniques allow for a maximum of 80% partial hepatectomy in rats, with low survival rates due to poor inflow control. The [...] Read more.
Background: Creating a model for acute liver failure in animal models is essential for research on liver regeneration and cancer. Current surgical techniques allow for a maximum of 80% partial hepatectomy in rats, with low survival rates due to poor inflow control. The common resection technique involves ligation at the liver lobe neck, causing peri-operative blood loss and postoperative blood loss. Methods: A 90% partial hepatectomy was performed on 5 rats using a bile duct-saving portal ligation technique, involving two hilum dissections for bile duct preservation. The first dissection controlled the blood supply to the median and left lateral lobes, and the second to the right inferior and superior lobes. Before closing, all rats were given 5 mL of 10% dextrose intraperitoneally and had access to ClearH2O DietGel Recovery and 20% dextrose. Weight and behavior were closely monitored for seven days post-operatively. Results: This method resulted in 100% survival, with a 3.1% increase in liver mass and 12.3% increase in liver-to-body mass ratio. Conclusions: This technique is the first bile duct-saving portal ligation for rodent models of acute liver failure, with long-term survival and complete hepatic regeneration. Our procedure offers a viable 90% hepatectomy model for research with improved survival and regeneration outcomes. Full article
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14 pages, 3085 KiB  
Article
SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy
by Ulrike Resch, Hubert Hackl, David Pereyra, Jonas Santol, Laura Brunnthaler, Joel Probst, Anna Sofie Jankoschek, Monika Aiad, Hendrik Nolte, Marcus Krueger, Patrick Starlinger and Alice Assinger
Int. J. Mol. Sci. 2024, 25(19), 10685; https://doi.org/10.3390/ijms251910685 - 4 Oct 2024
Cited by 3 | Viewed by 1926
Abstract
Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially [...] Read more.
Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknown. Methods: Our study included nine patients with hepatocellular carcinoma (HCC) undergoing PHx: three patients with PHLF, three patients undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, and three matched controls without complications after PHx. Patient plasma was collected before PHx as well as 1 and 5 days after. EVs were isolated by ultracentrifugation, and extracted proteins were subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell lines. Results: We identified 2625 and quantified 2570 proteins in the EVs of PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF patients compared to those undergoing ALPPS. The EV proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, and intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodelling and the metabolic and cell cycle pathways, already present before PHx. Conclusions: Longitudinal proteomic analysis of the EVs circulating in the plasma of human patients undergoing PHx uncovers proteomic signatures associated with PHLF, which reflect dying hepatocytes and endothelial cells and were already present before PHx. Full article
(This article belongs to the Special Issue Characterization of Extracellular Vesicles in Disease)
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12 pages, 4455 KiB  
Article
HMGB1-Mediated Cell Death—A Crucial Element in Post-Hepatectomy Liver Failure
by Laura Brunnthaler, Thomas G. Hammond, David Pereyra, Jonas Santol, Joel Probst, Valerie Laferl, Ulrike Resch, Monika Aiad, Anna Sofie Janoschek, Thomas Gruenberger, Hubert Hackl, Patrick Starlinger and Alice Assinger
Int. J. Mol. Sci. 2024, 25(13), 7150; https://doi.org/10.3390/ijms25137150 - 28 Jun 2024
Cited by 3 | Viewed by 1813
Abstract
Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 [...] Read more.
Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 (HMGB1), a key damage-associated molecular pattern (DAMP) released by hepatocytes, in liver recovery post LR in patients and animal models. Plasma from 96 LR patients and liver tissues from a subset of 24 LR patients were analyzed for HMGB1 levels, and associations with PHLF and liver injury markers were assessed. In a murine LR model, the HMGB1 inhibitor glycyrrhizin, was administered to assess its impact on liver regeneration. Furthermore, plasma levels of keratin-18 (K18) and cleaved cytokeratin-18 (ccK18) were quantified to assess suitability as predictive biomarkers for PHLF. Patients experiencing PHLF exhibited elevated levels of intrahepatic and circulating HMGB1, correlating with markers of liver injury. In a murine LR model, inhibition of HMGB1 improved liver function, reduced steatosis, enhanced regeneration and decreased hepatic cell death. Elevated levels of hepatic cell death markers K18 and ccK18 were detected in patients with PHLF and correlations with levels of circulating HMGB1 was observed. Our study underscores the therapeutic and predictive potential of HMGB1 in PHLF mitigation. Elevated HMGB1, K18, and ccK18 levels correlate with patient outcomes, highlighting their predictive significance. Targeting HMGB1 enhances liver regeneration in murine LR models, emphasizing its role in potential intervention and prediction strategies for liver surgery. Full article
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26 pages, 762 KiB  
Review
Challenges and Opportunities for Precision Surgery for Colorectal Liver Metastases
by Robert Michael O’Connell and Emir Hoti
Cancers 2024, 16(13), 2379; https://doi.org/10.3390/cancers16132379 - 28 Jun 2024
Cited by 1 | Viewed by 2202
Abstract
The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy [...] Read more.
The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy for their disease, long-term survival has been shown. Precision surgery—the idea of careful patient selection and targeting of surgical intervention, such that treatments shown to be proven to benefit on a population level are the optimal treatment for each individual patient—is the new paradigm of care. Key to this is the understanding of tumour molecular biology and clinically relevant mutations, such as KRAS, BRAF, and microsatellite instability (MSI), which can predict poorer overall outcomes and a poorer response to systemic therapy. The emergence of immunotherapy and hepatic artery infusion (HAI) pumps show potential to convert previously unresectable disease to resectable disease, in addition to established systemic and locoregional therapies, but the surgeon must be wary of poor-quality livers and the spectre of post-hepatectomy liver failure (PHLF). Volume modulation, a cornerstone of hepatic surgery for a generation, has been given a shot in the arm with the advent of liver venous depletion (LVD) ensuring significantly more hypertrophy of the future liver remnant (FLR). The optimal timing of liver resection for those patients with synchronous disease is yet to be truly established, but evidence would suggest that those patients requiring complex colorectal surgery and major liver resection are best served with a staged approach. In the operating room, parenchyma-preserving minimally invasive surgery (MIS) can dramatically reduce the surgical insult to the patient and lead to better perioperative outcomes, with quicker return to function. Full article
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10 pages, 1166 KiB  
Article
Significance of Prediction Models for Post-Hepatectomy Liver Failure Based on Type IV Collagen 7s Domain in Patients with Hepatocellular Carcinoma
by Takuma Okada, Hiroji Shinkawa, Satsuki Taniuchi, Masahiko Kinoshita, Kohei Nishio, Go Ohira, Kenjiro Kimura, Shogo Tanaka, Ayumi Shintani, Shoji Kubo and Takeaki Ishizawa
Cancers 2024, 16(10), 1938; https://doi.org/10.3390/cancers16101938 - 20 May 2024
Cited by 1 | Viewed by 1353
Abstract
Background: Previous studies have attempted to establish predictive models for post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) undergoing liver resection. However, a versatile and useful predictive model for PHLF remains to be developed. Therefore, we aimed to develop predictive models [...] Read more.
Background: Previous studies have attempted to establish predictive models for post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) undergoing liver resection. However, a versatile and useful predictive model for PHLF remains to be developed. Therefore, we aimed to develop predictive models for PHLF based on type IV collagen 7s domain (7s collagen) in patients with HCC. Methods: We retrospectively collected data from 972 patients with HCC who had undergone initial curative liver resection between February 2000 and December 2020 at our hospital. Multivariate logistic regression analysis using a restricted cubic spline was performed to evaluate the effect of 7s collagen on the incidence of PHLF. A nomogram was developed based on 7s collagen. Results: PHLF grades B or C were identified in 104 patients (11%): 98 (10%) and 6 (1%) PHLF grades B and C, respectively. Multivariate logistic regression analysis revealed that the preoperative serum level of 7s collagen was significantly associated with a proportional increase in the risk of PHLF, which was confirmed in both laparoscopic and open liver resections. A nomogram was developed based on 7s collagen, with a concordance index of 0.768. The inclusion of 7s collagen values in the predictive model increased the predictive accuracy. Conclusion: The findings highlight the efficacy of the serum level of 7s collagen as a predictive factor for PHLF. Our novel nomogram using 7s collagen may be useful for predicting the risk of PHLF. Full article
(This article belongs to the Special Issue Advances in the Treatment of Hepatocellular Carcinoma)
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19 pages, 2509 KiB  
Article
The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study
by Florian Primavesi, Thomas Senoner, Sophie Schindler, Aleksandar Nikolajevic, Pietro Di Fazio, Georg Csukovich, Silvia Eller, Bettina Neumayer, Markus Anliker, Eva Braunwarth, Rupert Oberhuber, Thomas Resch, Manuel Maglione, Benno Cardini, Thomas Niederwieser, Silvia Gasteiger, Eckhard Klieser, Herbert Tilg, Stefan Schneeberger, Daniel Neureiter, Dietmar Öfner, Jakob Troppmair and Stefan Stättneradd Show full author list remove Hide full author list
Antioxidants 2024, 13(5), 590; https://doi.org/10.3390/antiox13050590 - 11 May 2024
Cited by 1 | Viewed by 2015
Abstract
Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according [...] Read more.
Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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20 pages, 4917 KiB  
Article
Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans
by Lysann Tietze, Madlen Christ, Jiyeon Yu, Peggy Stock, Sandra Nickel, Annelie Schulze, Michael Bartels, Hans-Michael Tautenhahn and Bruno Christ
Cells 2024, 13(6), 529; https://doi.org/10.3390/cells13060529 - 17 Mar 2024
Cited by 2 | Viewed by 2149
Abstract
Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice [...] Read more.
Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice increased hepatic THBS1, downstream transforming growth factor-β3, and perturbation of liver tissue homeostasis. All these events were ameliorated by hepatic transfusion of human bone marrow-derived MSCs. Treatment attenuated platelet and macrophage recruitment to the liver, both major sources of THBS1. By mitigating THBS1, MSCs muted surgery-induced tissue deterioration and dysfunction, and thus supported post-hepatectomy regeneration. After liver surgery, patients displayed increased tissue THBS1, which is associated with functional impairment and may indicate a higher risk of post-surgery complications. Since liver dysfunction involving THBS1 improves with MSC treatment in various animal models, it seems feasible to also modulate THBS1 in humans to impede post-surgery acute liver failure. Full article
(This article belongs to the Section Stem Cells)
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12 pages, 958 KiB  
Article
Prevention of Post-Hepatectomy Liver Failure in Cirrhotic Patients Undergoing Minimally Invasive Liver Surgery for HCC: Has the Round Ligament to Be Preserved?
by Marco Vivarelli, Federico Mocchegiani, Taiga Wakabayashi, Federico Gaudenzi, Daniele Nicolini, Malek A. Al-Omari, Grazia Conte, Alessandra Borgheresi, Andrea Agostini, Roberta Rossi, Yoshiki Fujiyama, Andrea Giovagnoni, Go Wakabayashi and Andrea Benedetti Cacciaguerra
Cancers 2024, 16(2), 364; https://doi.org/10.3390/cancers16020364 - 15 Jan 2024
Cited by 2 | Viewed by 2244
Abstract
Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The [...] Read more.
Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The aim of this study was to assess whether the preservation of the round ligament (RL) may mitigate portal hypertension, thus decreasing the risk of PHLF and ascites in cirrhotic patients while undergoing minimally invasive liver surgery (MILS). All the cirrhotic patients who underwent MILS for HCC from 2016 to 2021 in two international tertiary referral centers were retrospectively analyzed, comparing cases with the RL preserved vs. those with the RL divided. Only patients with cirrhosis ≥ Child A6, portal hypertension, and ICG-R15 > 10% were included. Main postoperative outcomes were compared, and the risk factors for postoperative ascites (severe PHLF, grade B/C) were investigated through a logistic regression. After the application of the selection criteria, a total of 130 MILS patients were identified, with 86 patients with the RL preserved and 44 with the RL divided. The RL-preserved group showed lower incidences of severe PHLF (7.0% vs. 20.5%, p = 0.023) and ascites (5.8% vs. 18.2%, p = 0.026) in comparison with the RL-divided group. After uni/multivariate analysis, the risk factors related to postoperative ascites were RL division and platelets < 92 × 103/µL, calculated with ROC analysis. The preservation of the round ligament during MILS may mitigate portal hypertension, preventing PHLF and ascites in cirrhotic patients with borderline liver function. Full article
(This article belongs to the Special Issue Efficacy and Complications of Liver Resection for Liver Cancer)
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15 pages, 3051 KiB  
Article
Predicting Safe Liver Resection Volume for Major Hepatectomy Using Artificial Intelligence
by Chol Min Kang, Hyung June Ku, Hyung Hwan Moon, Seong-Eun Kim, Ji Hoon Jo, Young Il Choi and Dong Hoon Shin
J. Clin. Med. 2024, 13(2), 381; https://doi.org/10.3390/jcm13020381 - 10 Jan 2024
Cited by 6 | Viewed by 2871
Abstract
(1) Background: Advancements in the field of liver surgery have led to a critical need for precise estimations of preoperative liver function to prevent post-hepatectomy liver failure (PHLF), a significant cause of morbidity and mortality. This study introduces a novel application of artificial [...] Read more.
(1) Background: Advancements in the field of liver surgery have led to a critical need for precise estimations of preoperative liver function to prevent post-hepatectomy liver failure (PHLF), a significant cause of morbidity and mortality. This study introduces a novel application of artificial intelligence (AI) in determining safe resection volumes according to a patient’s liver function in major hepatectomies. (2) Methods: We incorporated a deep learning approach, incorporating a unique liver-specific loss function, to analyze patient characteristics, laboratory data, and liver volumetry from computed tomography scans of 52 patients. Our approach was evaluated against existing machine and deep learning techniques. (3) Results: Our approach achieved 68.8% accuracy in predicting safe resection volumes, demonstrating superior performance over traditional models. Furthermore, it significantly reduced the mean absolute error in under-predicted volumes to 23.72, indicating a more precise estimation of safe resection limits. These findings highlight the potential of integrating AI into surgical planning for liver resections. (4) Conclusion: By providing more accurate predictions of safe resection volumes, our method aims to minimize the risk of PHLF, thereby improving clinical outcomes for patients undergoing hepatectomy. Full article
(This article belongs to the Special Issue Advances in Hepatobiliary Surgery)
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14 pages, 710 KiB  
Article
Safety and Survival Outcomes of Liver Resection following Triple Combination Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma
by Yin Long, Jue Huang, Jianguo Liao, Dongbo Zhang, Ziqi Huang, Xiaodong He and Lei Zhang
Cancers 2023, 15(24), 5878; https://doi.org/10.3390/cancers15245878 - 17 Dec 2023
Cited by 16 | Viewed by 2699
Abstract
Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular [...] Read more.
Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien–Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356–1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807–1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC. Full article
(This article belongs to the Section Cancer Therapy)
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