Hepatectomy Research Articles

A novel low-cost high-fidelity porcine model of liver metastases for simulation training in robotic parenchyma-preserving liver resection.

In the era of minimally invasive surgery (MIS), parenchyma-preserving liver resections are gaining prominence with the potential to offer improved perioperative outcomes without compromising oncological safety. The surgeon learning curve remains challenging, and simulation plays a key role in surgical training. Existing simulation models can be limited by suboptimal fidelity and high cost. We describe a novel, reproducible, high-fidelity, low-cost liver metastases model using porcine livers from adult Landrace pigs, with porcine perinephric fat used to simulate subcapsular metastases. This model was then utilised in a training session for surgical trainees performing robotic parenchyma-preserving surgery (PPS) under the guidance of expert robotic surgeons, with feedback being recorded. Trainees rated the model highly on its fidelity to human liver simulation (median score 9), tissue handling (median score 8), and overall usefulness (median score 9). Tissue handling was felt to simulate in vivo liver resection closely, while suggestions for improvement included adding simulated blood flow. This is a novel, low-cost, high-fidelity simulation model of liver metastases with high acceptability to surgical trainees, which could be readily adopted by other training centres.

Laparoscopic versus open surgery for liver resection: a multicenter cohort study

The relative risk and benefits of Laparoscopic liver resection (LLR) are still controversial. This study aimed to evaluate perioperative and survival outcomes for three primary malignant liver tumors related outcomes following LLR. Data from three Homogeneous-High-Volume-Expert-Centers were collected. Multivariable logistic regression analysis was performed for the association between LLR, and major complications defined as Clavien-Dindo Classification grade ≥ II. Multivariable Cox proportional hazards regression was used to explore the impact of LLR on primary malignant liver tumor survival. Overall, 5886 patients underwent liver resection, of which 1991 underwent LLR. After adjusting for covariables, LLR had significantly lower rate of CDC grade ≥ II (OR = 0.56, 95% CI: 0.48–0.67, P < 0.001). Interaction analysis showed that LLR had significant association with sex, drinking status, history of abdominal surgery, and platelet count (all P < 0.05). The overall survival for each primary malignant liver tumor shown potential risk but without significantly different between LLR and OLR (all P > 0.05). LLR was associated with lower rate of major complications, especially in women, non-drinkers, those without a history of abdominal surgery, and those with normal platelet. For primary malignant liver tumors, the survival outcomes did not differ significantly between LLR and OLR.

Myeloid derived suppressor cells mediate hepatocyte proliferation and immune suppression during liver regeneration following resection.

Liver regeneration following resection is a complex process relying on coordinated pathways and cell types in the remnant organ. Myeloid-Derived Suppressor Cells (MDSCs) have a role in liver regeneration-related angiogenesis but other roles they may play in this process remain to be elucidated. In this study, we sought to examine the effect of G-MDSCs on hepatocytes proliferation and immune modulation during liver regeneration. Global gene expression profiling of regenerating hepatocytes in mice with CD11b+Ly6G+ MDSCs (G-MDSCs) depletion revealed disrupted transcriptional progression from day one to day two after major liver resection. Key genes and pathways related to hepatocyte proliferation and immune response were differentially expressed upon MDSC depletion. Hepatocytes cellularity increased when co-cultured with G-MDSCs, or treated with amphiregulin, which G-MDSCs upregulate during regeneration. Cytometry by time-of-flight (CyTOF) analysis of the intra-liver immune milieu upon MDSC depletion during regeneration demonstrated increased natural killer cell proportions, alongside changes in other immune cell populations. Taken together, these results provide evidence that MDSCs contribute to early liver regeneration by promoting hepatocyte proliferation and modulating the intra-liver immune response, and illuminate the multifaceted role of MDSCs in liver regeneration.

Initial Experience With Robotic Liver Resection in the United States.

This study's aim was to show the feasibility and safety of robotic liver resection (RLR) even without extensive experience in major laparoscopic liver resection (LLR). A single center, retrospective analysis was performed for consecutive liver resections for solid liver tumors from 2014 to 2022. The analysis included 226 liver resections, comprising 127 (56.2%) open surgeries, 28 (12.4%) LLR, and 71 (31.4%) RLR. The rate of RLR increased and that of LLR decreased over time. In a comparison between propensity score matching-selected open liver resection and RLR (41:41), RLR had significantly less blood loss (384 ± 413 vs 649 ± 646mL, P = .030) and shorter hospital stay (4.4 ± 3.0 vs 6.4 ± 3.7 days, P = .010), as well as comparable operative time (289 ± 123 vs 290 ± 132 mins, P = .954). A comparison between LLR and RLR showed comparable perioperative outcomes, even with more surgeries with higher difficulty score included in RLR (5.2 ± 2.7 vs 4.3 ± 2.5, P = .147). The analysis of the learning curve in RLR demonstrated that blood loss, conversion rate, and complication rate consistently improved over time, with the case number required to achieve the learning curve appearing to be 60 cases. The findings suggest that RLR is a feasible, safe, and acceptable platform for liver resection, and that the safe implementation and dissemination of RLR can be achieved without solid experience of LLR.

Association Of Serum Prothrombin Index With Early Post-Operative Complications Following Liver Resection

Introduction: The Prothrombin Index (PI) is a critical measure of coagulation status, reflecting the liver's ability to synthesize clotting factors. In the context of liver resection, a procedure associated with a significant risk of bleeding and other complications, the assessment of PI becomes paramount. This study investigates the association between serum Prothrombin Index and early postoperative complications following liver resection. Methods: This Prospective observational study was conducted among the indoor patients of the Hepatobiliary unit of the surgery department in Dhaka Medical College Hospital, from 1st January 2023 to 29th December 2023. All patients admitted to the hepatobiliary unit of the department of surgery, Dhaka Medical College Hospital were considered as the study population. A total of 40 patients were selected as study subjects through a purposive sampling technique. Data were analyzed by Statistical Package for Social Sciences (SPSS) version 20.0. Result: In the early postoperative period, the association between prothrombin index (PI) and various complications was assessed. Regarding bile leak, no statistically significant association was observed, with the probability of bile leak being 0.237 for patients with a PI &lt;50%. In contrast, a significant association was found between PI and postoperative bleeding, where a PI &lt;50% showed a probability of 0.04 for hemorrhage, making this result statistically significant. Lastly, the association between PI and sepsis revealed no significant findings, with a probability of 0.479 for sepsis in patients with a PI &lt;50%. Overall, a lower PI was significantly linked to an increased risk of postoperative bleeding, but not to bile leak or sepsis. Conclusion: The study findings highlight the clinical importance of assessing both the initial and postoperative Prothrombin Index concerning outcomes following liver resection. Consequently, utilizing the initial and early postoperative Prothrombin Index as a clinical parameter can enhance the optimization of postoperative patient care.

99mTc-GSA scintigraphy and modified albumin–bilirubin score can be complementary to ICG for predicting posthepatectomy liver failure

BackgroundPosthepatectomy liver failure (PHLF) remains a severe complication after liver resection. This retrospective study investigated the correlation of three hepatic functional tests and whether 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy and modified albumin–bilirubin (ALBI) score are useful for predicting PHLF.MethodsThis retrospective cohort study included 413 consecutive patients undergoing hepatectomies between January 2017 and December 2020. To evaluate preoperative hepatic functional reserve, modified ALBI grade, indocyanine green clearance (ICG-R15), and 99mTc-GSA scintigraphy (LHL15) were examined before scheduled hepatectomy. Based on a retrospective chart review, multivariable logistic regression analysis adjusted for confounding factors was performed to confirm that mALBI, ICG-R15, and LHL15 are independent risk factors for PHLF.ResultsICG-R15 and LHL15 were moderately correlated (r = − 0.61) but this correlation weakened when ICG-R15 was about ≥ 20. Weak correlations were observed between LHL15 and ALBI score (r = − 0.269) and ALBI score and ICG-R15 (r = 0.339). Of 413 patients, 66 (19%) developed PHLF (20 grade A, 44 grade B, 2 grade C). Multivariable logistic regression analyses, major hepatectomy (P < 0.001), mALBI grade (P = 0.01), ICG-R15 (P < 0.001), and Esophagogastric varices (P = 0.007) were significant independent risk factors for PHLF. Subgroup analysis showed that ICG-R15 < 19, major hepatectomy, and mALBI grade and ICG-R15 ≥ 19, major hepatectomy, LHL15, and Esophagogastric varices were significant independent risk factors for PHLF (P = 0.033, 0.017, 0.02, 0.02, and 0.001, respectively).ConclusionLHL15, the assessment of Esophagogastric varices, and mALBI grade are complementary to ICG-R15 for predicting PHLF risk.

The Inter-Laennec Approach for Liver Tumors in Contact with Hepatic Veins in Laparoscopic Liver Resection.

Patients with liver tumors that are in contact with the major hepatic veins may require hepatic vein resection to achieve an adequate surgical margin; however, the potential for venous congestion and impaired remnant liver function must be considered. We introduce the anatomy of the hepatic vein related to Laennec's capsule as well as the surgical techniques to overcome these limitations in the laparoscopic approach.1,2 PATIENTS AND METHODS: A patient with hepatocellular carcinoma underwent resection of the paracaval portion of the caudate lobe. A 4.5-cm tumor was located on the hepatic hilum, compressing the middle and right hepatic veins (MHV and RHV). The Laennec's capsule around the hepatic veins consists of cardiac and hepatic layers. In the inter-Laennec approach, the hepatic veins and inferior vena cava were continuously exposed from the root side, during entry into the space between the hepatic and cardiac Laennec's capsules.3,4 Hence, the cardiac Laennec's capsule was preserved on the venous side, and the strength of the hepatic vein walls was maintained without exposing the tumor. Parenchymal transection was performed while preserving the MHV and RHV. The operative time was 331 min, with minimal estimated blood loss. The patient was discharged on postoperative day 6 without complications. A pathological examination revealed the presence of focal capsular invasion; however, the surgical margin was maintained by leaving the hepatic Laennec's capsule on the tumor side. Understanding the structure of the Laennec's capsule can contribute to the establishment of safe and feasible liver resection techniques.

New criteria for preoperative liver function assessment with safety margins to avoid postoperative mortality during liver resection for hilar cholangiocarcinoma.

New criteria for preoperative liver function assessment with safety margins to avoid postoperative mortality during liver resection for hilar cholangiocarcinoma.

Posthepatectomy Liver Failure in Patients with Splenomegaly Induced by Induction Chemotherapy for Colorectal Liver Metastases.

With advances in chemotherapy, conversion surgery is often performed for initially unresectable colorectal cancer liver metastasis (CLM). However, unexpected posthepatectomy liver failure (PHLF) is sometimes associated with chemotherapy-associated liver injuries following long-term chemotherapy. We aimed to identify predictive factors for PHLF after conversion surgery for initially unresectable CLM. We retrospectively identified 774 consecutive patients who underwent initial liver resections for histologically confirmed CLMs between 2010 and 2019 at our institute. We enrolled 107 patients with initially unresectable CLMs. Clinicopathological characteristics were evaluated to determine their association with PHLF. Logistic regression analysis was performed to analyze the predictors of PHLF. Among the 107 patients, PHLF occurred in 15 cases (14%). Multivariate analysis revealed that splenomegaly during preoperative chemotherapy (> 135%) was an independent risk factor for PHLF (P = 0.002; odds ratio 14.30; 95% confidence interval 2.69-76.08). In the analysis limited to the splenomegaly group, lower platelet counts, increased blood loss and operative times, and large liver resection areas (> 100 cm2) were significant risk factors for PHLF (P = 0.018, 0.043, 0.020, and 0.024, respectively). Among them, a liver resection area > 100 cm2 can be calculated preoperatively and correlate with a complex hepatectomy. These findings could help predict PHLF after conversion surgery and induction chemotherapy for initially unresectable CLMs. Careful decisions, including detailed procedures and timing of hepatectomy, should be made before conversion hepatectomy in patients who develop splenomegaly after induction chemotherapy and require complex hepatectomies with a large liver resection area.

Impact of microvascular invasion risk on tumor progression of hepatocellular carcinoma after conventional transarterial chemoembolization.

To assess tumor progression in patients with hepatocellular carcinoma (HCC) without macrovascular invasion who underwent treatment with conventional transarterial chemoembolization (cTACE) based on microvascular invasion (MVI) risk within 2 years. This retrospective investigation comprised adult patients with HCC who had either liver resection or cTACE as their first treatment from January 2016 to December 2021. A predictive model for MVI was developed and validated using preoperative clinical and MRI data from patients with HCC treated with liver resection. The MVI predictive model was applied to patients with HCC receiving cTACE, and differences in tumor progression between the MVI high- and low-risk groups were examined throughout 2 years. The MVI prediction model incorporated nonsmooth margin, intratumoral artery, incomplete or absent tumor capsule, and tumor DWI/T2WI mismatch. The area under the receiver operating characteristic curve (AUC) for the prediction model, in the training cohort, was determined to be 0.904 (95% CI, 0.862-0.946), while in the validation cohort, it was 0.888 (0.782-0.994). Among patients with HCC undergoing cTACE, those classified as high risk for MVI possessed a lower rate of achieving a complete response after the first tumor therapy and a higher risk of tumor progression within 2 years. The MVI prediction model developed in this study demonstrates a considerable degree of accuracy. Patients at high risk for MVI who underwent cTACE treatment exhibited a higher risk of tumor progression within 2 years.

Short- and long-term outcomes of liver resection with hepatic vein reconstruction for liver tumors: A nationwide multicenter survey.

This study clarifies the short- and long-term outcomes of liver resection with hepatic vein (HV) reconstruction for liver tumors and identifies the risk factors for poor outcome. We contacted 263 specialized centers in Japan and collected data on this surgical procedure. Patient characteristics, surgical procedures, and outcomes were then analyzed. A total of 187 patients were enrolled from 36 institutions. Grade C post-hepatectomy liver failure (PHLF) and in-hospital mortality were 3.2% and 1.6%, respectively. The median overall survival (OS) and recurrence-free survival (RFS) were 49.9 and 9.8 months, respectively. Surgical outcomes, OS and RFS did not differ among three types of liver tumors, colorectal liver metastasis (CRLM) (n = 127), hepatocellular carcinoma (n = 27), and intrahepatic cholangiocarcinoma (n = 27). Patients with CRLM and seven or more courses of preoperative chemotherapy had significantly worse OS. Compared with HV reconstruction for securing liver remnant (LR) function (n = 148), reconstruction of the only main HV remaining in the LR (n = 39) had significantly worse short-term outcomes, but did not result in increased mortality, and showed equivalent OS and RFS. Liver resection with HV reconstruction can be achieved safely and contributes to a relatively good long-term outcome for patients with advanced liver malignancies.

Classifying histopathological growth patterns for resected colorectal liver metastasis with a deep learning analysis.

Histopathological growth patterns are one of the strongest prognostic factors in patients with resected colorectal liver metastases. Development of an efficient, objective and ideally automated histopathological growth pattern scoring method can substantially help the implementation of histopathological growth pattern assessment in daily practice and research. This study aimed to develop and validate a deep-learning algorithm, namely neural image compression, to distinguish desmoplastic from non-desmoplastic histopathological growth patterns of colorectal liver metastases based on digital haematoxylin and eosin-stained slides. The algorithm was developed using digitalized whole-slide images obtained in a single-centre (Erasmus MC Cancer Institute, the Netherlands) cohort of patients who underwent first curative intent resection for colorectal liver metastases between January 2000 and February 2019. External validation was performed on whole-slide images of patients resected between October 2004 and December 2017 in another institution (Radboud University Medical Center, the Netherlands). The outcomes of interest were the automated classification of dichotomous hepatic growth patterns, distinguishing between desmoplastic hepatic growth pattern and non-desmoplatic growth pattern by a deep-learning model; secondary outcome was the correlation of these classifications with overall survival in the histopathology manual-assessed histopathological growth pattern and those assessed using neural image compression. Nine hundred and thirty-two patients, corresponding to 3.641 whole-slide images, were reviewed to develop the algorithm and 870 whole-slide images were used for external validation. Median follow-up for the development and the validation cohorts was 43 and 29 months respectively. The neural image compression approach achieved significant discriminatory power to classify 100% desmoplastic histopathological growth pattern with an area under the curve of 0.93 in the development cohort and 0.95 upon external validation. Both the histopathology manual-scored histopathological growth pattern and neural image compression-classified histopathological growth pattern achieved a similar multivariable hazard ratio for desmoplastic versus non-desmoplastic growth pattern in the development cohort (histopathology manual score: 0.63 versus neural image compression: 0.64) and in the validation cohort (histopathology manual score: 0.40 versus neural image compression: 0.48). The neural image compression approach is suitable for pathology-based classification tasks of colorectal liver metastases.

Cytoreductive treatment with HIPEC and partial liver resection in patients with peritoneal and liver metastases from colorectal cancer

Cytoreductive treatment with HIPEC and partial liver resection in patients with peritoneal and liver metastases from colorectal cancer

Liver Resection With Extrahepatic Disease: A Population-Based Analysis of Thoughtful Selection.

The oncologic benefit of liver resection for colorectal liver metastases (CRLM) in the setting of concurrent extrahepatic disease (EHD) is controversial. We performed a population-based, cross-sectional study to determine the practice patterns and overall survival (OS) of patients with CRLM + EHD who underwent liver resection. Patients with CRLM + EHD were identified using the California Cancer Registry from 2000 to 2019. Records were linked to the Office of Statewide Health Planning Inpatient Database. Patient demographics, clinical characteristics, and survival were compared between CRLM + EHD patients with and without liver resection. Of 170 978 patients with CRLM, 62 003 (36%) had concurrent EHD (CRLM + EHD). In all, 3736 (6%) of CRLM + EHD underwent liver resection compared to 22% of patients with liver limited CRLM. Compared to CRLM + EHD without liver resection, CRLM + EHD with resection were younger, had fewer comorbidities, received higher frequencies of perioperative chemotherapy, and were more likely to have only a single site of EHD rather than multiple sites. Median OS was significantly higher for CRLM + EHD with resection compared to without (52 vs. 27 months, HR 0.46 [95% CI 0.44-0.47], p < 0.001). Regarding the location of EHD, this survival benefit was observed with liver resection for lung, peritoneal, intraabdominal lymph nodes, ovarian, and bone metastases. In a large population-based setting, subsets of CRLM + EHD patients that undergo liver resection are associated with prolonged survival. These results support surgery with thoughtful patient selection to optimize survival outcomes in this population.

ASO Author Reflections: Achievements of Textbook Outcomes for Hepatocellular Carcinoma Patients After Liver Resection: The Role of the Number of Metabolic Syndrome Risk Factors.

ASO Author Reflections: Achievements of Textbook Outcomes for Hepatocellular Carcinoma Patients After Liver Resection: The Role of the Number of Metabolic Syndrome Risk Factors.

Simple Trocar Placement for Robotic Liver and Pancreatic Surgery: Multiple Access Devices at 5-cm Single Umbilicus Incision with 2 Robotic Ports.

Robotic trocars are recommended to be placed 6-8 cm apart, and assistant trocars are placed 7 cm away from the horizontal line of the robotic trocar placement. However, adhering to these rules may be difficult, particularly in lean patients. This study aims to demonstrate our standardized simple trocar placement, 5-cm single umbilicus incision + 2 ports for robotic liver resection (RLR) and robotic pancreaticoduodenectomy (RPD). During 2022-2024, patients undergoing RLR and RPD at The University of Tokyo were identified from a prospectively maintained database. Our standardized trocar placement consisted of multiple access devices at the 5-cm umbilicus incision, including two robotic trocars and one assistant trocar, and two other robotic trocars inserted to shape a hemi-circle around the surgical object. A total of 29 and 31 consecutive patients underwent RLR and RPD, respectively. The 5-cm single umbilicus incision + 2 ports method was used in 82.8% of patients undergoing RLR and 100% of patients undergoing RPD. No patients undergoing RLR developed hepatic insufficiency and bile leakage with the median postoperative hospital stay of 5 days. No patients undergoing RPD developed clinically relevant pancreatic fistula, delayed gastric emptying, and bile leakage with the median postoperative hospital stay of 8 days. Our standardized trocar placement technique is simple and widely feasible for lean-to-obese patients, allowing for RLR and RPD while minimizing incisions for patients.

Combined preoperative albumin bilirubin score and hepatectomy percentage for evaluate the liver regeneration after partial hepatectomy

Surgical resection is a pivotal therapeutic approach for addressing hepatic space-occupying lesions, with liver volume restoration and hepatic functional recovery being crucial for assessing surgical prognosis. The preoperative albumin-bilirubin (ALBI) score, encompassing serum albumin and bilirubin levels, can be determined via blood analysis, effectively mitigating human error and providing an accurate depiction of liver function. The hepatectomy ratio, which is the proportion of the liver volume removed to the total liver volume, is critical in preserving an adequate liver tissue volume to ensure postoperative hepatic functional compensation, minimize surgical complications, and reduce mortality rates. Incorporating the preoperative ALBI score and hepatectomy ratio aids surgeons in assessing the optimal timing and extent of partial hepatectomy. The introduction of preoperative albumin bilirubin score and hepatectomy percentage is beneficial for the surgeons to evaluate the timing and magnitude of partial liver resection.

ALKBH5 Protects Against Hepatic Ischemia–Reperfusion Injury by Regulating YTHDF1-Mediated YAP Expression

Ischemia/reperfusion (I/R) injury with severe cell death is a major complication involved in liver transplantation and resection. The identification of key regulators improving hepatocyte activity may provide potential strategies to clinically resolve I/R-induced injury. N6-methyladenosine (m6A) RNA modification is essential for tissue homeostasis and pathogenesis. However, the potential involvement of m6A in the regulation of hepatocyte activity and liver injury has not been fully explored. In the present study, we found that hepatocyte AlkB homolog H5 (ALKBH5) levels were decreased both in vivo and in vitro I/R models. Hepatocyte-specific ALKBH5 overexpression effectively attenuated I/R-induced liver necrosis and improved cell proliferation in mice. Mechanistically, ALKBH5-mediated m6A demethylation improved the mRNA stability of YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Yes-associated protein (YAP). In conclusion, ALKBH5 is a regulator of hepatic I/R injury that improves hepatocyte repair and proliferation by maintaining YTHDF1 stability and YAP content. The ALKBH5–m6A–YTHDF1–YAP axis represents promising therapeutic targets for hepatic I/R injury to improve the prognosis of liver surgery.

Development of a novel difficulty scoring system for laparoscopic liver resection procedure in patients with intrahepatic duct stones

Development of a novel difficulty scoring system for laparoscopic liver resection procedure in patients with intrahepatic duct stones

Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma

AbstractAimThe relationship between sarcopenia, tumor‐infiltrating lymphocytes (TILs), and long‐term survival in patients with hepatocellular carcinoma (HCC) has not been investigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILs in patients with HCC.MethodsWe included 351 patients with HCC following liver resection. Sarcopenia was defined based on the skeletal muscle index using computed tomography. Tumor‐infiltrating CD4+ and CD8+ T cells, perforin, and granzyme B were examined in liver resection specimens.ResultsSarcopenia patients had a significantly lower lymphocyte count (p = 0.003), prognostic nutritional index (p = 0.017), and CD4+ and CD8+ T cell counts (p = 0.008 and p = 0.006, respectively). The overall survival (OS) and recurrence‐free survival (RFS) rates of sarcopenia patients were significantly lower than non‐sarcopenia patients (both p &lt; 0.001). Multivariate analysis revealed that sarcopenia and low CD8 levels were strong independent poor prognostic factors for OS and RFS (both p &lt; 0.001). Regardless of sarcopenia, patients with high CD8 levels had significantly better OS and RFS rates and increased expression of perforin and granzyme B. Particularly, sarcopenia patients with high CD8 levels had much better OS and RFS than those with low CD8 levels and were even comparable to non‐sarcopenia patients with high CD8 levels.ConclusionsSarcopenia and low CD8 levels are strong independent poor prognostic factors in patients with HCC. Furthermore, sarcopenia patients with high CD8 levels had favorable survival and activated local immunity, suggesting that tumor‐infiltrating CD8+ T cells may play a functionally important role in sarcopenia patients.