Textbook outcome in patients with biliary duct injury during cholecystectomy.

BACKGROUND: Iatrogenic bile duct injury (BDI) during cholecystectomy is associated with a complex and heterogeneous management owing to the burden of morbidity until their definitive treatment. This study aimed to define the textbook outcomes (TOs) after BDI with the purpose to indicate the ideal treatment and to improve it management. METHODS: We collected data from patients with an BDI between 1990 and 2022 from 27 hospitals. TO was defined as a successful conservative treatment of the iatrogenic BDI or only minor complications after BDI or patients in whom the first repair resolves the iatrogenic BDI without complications or with minor complications. RESULTS: We included 808 patients and a total of 394 patients (46.9%) achieved TO. Overall complications in TO and non-TO groups were 11.9% and 86%, respectively (P < .001). Major complications and mortality in the non-TO group were 57.4% and 9.2%, respectively. The use of end-to-end bile duct anastomosis repair was higher in the non-TO group (23.1 vs 7.8, P < .001). Factors associated with achieving a TO were injury in a specialized center (adjusted odds ratio [aOR], 4.01; 95% CI, 2.68-5.99; P < .001), transfer for a first repair (aOR, 5.72; 95% CI, 3.51-9.34; P < .001), conservative management (aOR, 5.00; 95% CI, 1.63-15.36; P = .005), or surgical management (aOR, 2.45; 95% CI, 1.50-4.00; P < .001). CONCLUSION: TO largely depends on where the BDI is managed and the type of injury. It allows hepatobiliary centers to identify domains of improvement of perioperative management of patients with BDI.

Explainable artificial intelligence prediction-based model in laparoscopic liver surgery for segments 7 and 8: an international multicenter study.

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Multimodal prehabilitation program in patients with resectable perihilar cholangiocarcinoma: keypoints for an implementation protocol and literature review.

BACKGROUND: Postoperative complications after perihilar cholangiocarcinoma surgical procedure are still very high. The implementation of a multimodal prehabilitation program could improve these outcomes. Based on our experience and that of the literature in hepatobiliary and pancreatic surgery, we propose a protocol to promote its implementation. METHODS: First, we performed a retrospective analysis of the implementation feasibility of a multimodal prehabilitation program in patients' candidates for elective perihilar cholangiocarcinoma surgery in our center. Second, we conducted a literature search of publications in PubMed until December 2022. Relevant data about hepato-pancreato-biliary surgery and prehabilitation programs in features and postoperative outcomes was analyzed. RESULTS: Since October 2020, 11 patients were evaluated for prehabilitation in our hospital. Two of them could not be resected intraoperatively due to disease extension. The median hospital stay was 10 days (iqr, 7-11). There were no major complications and 1 patient died. Of a total of 17 articles related to prehabilitation in hepato-biliary-pancreatic surgery, no reports focusing exclusively on perihilar cholangiocarcinoma were found. Six of the studies had nutritional therapies in addition to physical interventions, and 12 studies used home-based exercise therapy. CONCLUSIONS: Based on our experience and the data obtained from other studies, a prehabilitation program could be useful to improve perioperative physical and mental fitness in patients' candidates for elective perihilar cholangiocarcinoma surgery. However, more well-designed studies are needed to allow us to obtain more evidence.

Liver Histology Predicts Liver Regeneration and Outcome in ALPPS: Novel Findings From A Multicenter Study.

BACKGROUND AND AIMS: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. METHODS: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. RESULTS: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively). CONCLUSIONS: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.

Impact of rapid hypertrophy of tourniquet associating liver partition and portal vein ligation in the tumor progression pathways compared to two stage hepatectomy in patients with colorectal liver metastases.

BACKGROUND: It is not known if the inflammatory phenomena related to highly accelerated regeneration activate any signaling pathways that are associated with a major stimulus to colorectal liver metastases (CRLM) disease in tourniquet associating liver partition and portal vein ligation for staged hepatectomy (T-ALPPS) compared to two stage hepatectomy (TSH). METHODS: Between January 2012 and April 2018, we prospectively performed biopsies from future liver remnant and deportalized lobe in CRLM patients undergoing T-ALPPS in both stages. Immunohistopathological analysis was performed on the above tissue samples and compared to biopsy samples from patients who underwent TSH for CRLM at our center between September 2000 and August 2011. RESULTS: A total of 42 patients (20 TSH and 22 T-ALPPS) were included. There were no differences in the rates of recurrence, overall survival or any of the factors analyzed relating to tumor progression between stages 1 and 2. Regarding the anti-tumor effect, there was a significant reduction in the number of T-CD8 infiltrates in the second stage of TSH (12.5 vs. 5.5, p = 0.02). CONCLUSION: The results suggest that liver regeneration with T-ALPPS does not induce higher tumor progression or significant immunological changes in the tumor environment when compared to classical TSH.

Long-term oncological outcomes for HALS/Hybrid vs pure laparoscopic approach in colorectal liver metastases: a propensity score matched analysis.

BACKGROUND: Studies comparing hand-assisted laparoscopic (HALS)/Hybrid and pure laparoscopic (PLS) resection for colorectal cancer liver metastasis have focused on short-term results, while long-term oncological outcomes remain understudied. METHODS: We established a multi-institutional retrospective cohort study from four centers with experience in minimally invasive surgery between 2004 and 2020. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Other endpoints analyzed were intraoperative and postoperative outcomes. Propensity score matching (PSM) was used to minimize baseline differences. RESULTS: A total of 219 HALS/Hybrid (57.8%) and 160 PLS (42.2%) patients were included. After PSM, 155 patients remained in each group. Operative time (182 vs. 248 min, p = 0.012), use of intraoperative ablation (12.3 vs. 4.5%, p = 0.024), positive resection margin (4.5 vs 13.2%, p = 0.012), and pringle time (21 vs. 37 min, p = 0.001) were higher in PLS group. DFS at 1, 3, 5, and 7 years in HALS/Hybrid and PLS groups were 65.4%, 39.3%, 37.5%, and 36.3% vs. 64.9%, 38.0%, 33.1%, and 33.1%, respectively (p = 0.84). OS at 1, 3, 5, and 7 years in HALS/Hybrid and PLS groups were 94.5%, 71.4%, 54.3%, and 46.0% vs. 96.0%, 68.5%, 51.2%, and 41.2%, respectively (p = 0.73). CONCLUSION: Our study suggests no differences in long-term oncologic outcomes between the two techniques. We discovered that longer total operative, pringle time, higher rates of intraoperative ablation, and positive resection margins were associated with PLS. These differences in favor of HALS/Hybrid could be due to a shorter learning curve and a greater ability to control hemorrhage.

Extreme In Situ Liver Surgery Under Total Vascular Exclusion with Right Hepatic Vein and Inferior Vena Cava Grafts for an Intrahepatic Cholangiocarcinoma.

In this multimedia article, we demonstrate an extreme in situ liver surgery under total vascular exclusion with right hepatic vein and inferior vena cava grafts for an intrahepatic cholangiocarcinoma in a centre with experience in highly complex hepatobiliary surgery and liver transplantation. This surgical approach after neoadjuvant chemotherapy provides an opportunity for surgical salvage in patients with large tumors invading the hepatocaval confluence. This patient was considered unresectable at another hospital and referred to our unit. We performed an accurate preoperative assessment with new generation 3D modelling to plan the type of vascular reconstruction that would allow adequate hepatic venous outflow and the volume of the future liver remnant sufficient to avoid postoperative liver failure. For hemodynamic management of the patient, we performed a total hepatic vascular exclusion with veno-venous bypass without intraoperative adverse events. We used a cryopreserved carotid artery graft after previously planning the most appropriate diameter and length for right hepatic vein reconstruction. The inferior vena cava was reconstructed with gore-tex graft. During the hospital stay there were no postoperative complications. The patient is free of disease. We conclude that patients with advanced malignant liver disease should always be referred to highly specialized liver surgery centers to assess the most appropriate oncological management and the possibility of surgical resectability.

Vascular injury during cholecystectomy: A multicenter critical analysis behind the drama.

BACKGROUND: The management of a vascular injury during cholecystectomy is still very complicated, especially in centers not specialized in complex hepatobiliary surgery. METHODS: This was a multi-institutional retrospective study in patients with vascular injuries during cholecystectomy from 18 centers in 4 countries. The aim of the study was to analyze the management of vascular injuries focusing on referral, time to perform the repair, and different treatments options outcomes. RESULTS: A total of 104 patients were included. Twenty-nine patients underwent vascular repair (27.9%), 13 (12.5%) liver resection, and 1 liver transplant as a first treatment. Eighty-four (80.4%) vascular and biliary injuries occurred in nonspecialized centers and 45 (53.6%) were immediately transferred. Intraoperative diagnosed injuries were rare in referred patients (18% vs 84%, P = .001). The patients managed at the hospital where the injury occurred had a higher number of reoperations (64% vs 20%, P ˂ .001). The need for vascular reconstruction was associated with higher mortality (P = .04). Two of the 4 patients transplanted died. CONCLUSION: Vascular lesions during cholecystectomy are a potentially life-threatening complication. Management of referral to specialized centers to perform multiple complex multidisciplinary procedures should be mandatory. Late vascular repair has not shown to be associated with worse results.

Machine Learning-Based Analysis in the Management of Iatrogenic Bile Duct Injury During Cholecystectomy: a Nationwide Multicenter Study.

BACKGROUND: Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels. METHODS: This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index. RESULTS: We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p < 0.01), treatment in specialized centers (p < 0.01), and surgical repair (p < 0.001) were associated with better prognosis. The risk-scoring model was 82.3% (79.0-85.3%, 95% confidence interval [CI]) and 71.7% (63.8-78.7%, 95% CI) accurate in predicting success in the development and validation cohorts, respectively. Surgical repair, successful initial repair, and repair between 2 and 6 weeks were associated with better outcomes. DISCUSSION: Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients.

Sex Disparities in Outcomes Following Major Liver Surgery: New Powers of Estrogen?

AIM: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies. BACKGROUND: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown. METHODS: Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t , χ 2 , or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion. RESULTS: Following major hepatectomy (Hx), males had more severe complications ( P =0.03) and higher liver dysfunction (MELD) P =0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126-2.89; P =0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01-3.69; P =0.045). Female patients displayed shorter interstage intervals (<2 weeks, 64% females versus 56% males, P =0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism. CONCLUSIONS: Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen's benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery.

Liver growth prediction in ALPPS - A multicenter analysis from the international ALPPS registry.

BACKGROUND: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR). METHODS: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula. RESULTS: A total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male. CONCLUSIONS: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.

Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score: is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS)?

Background: Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is not always reliable with currently available scores, particularly in patients with primary liver tumor. This study aims to (I) to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and (II) to create a score predicting 90-day mortality preoperatively. Methods: Thirteen high-volume centers participated in this retrospective multicentric study. A risk analysis based on patient characteristics, underlying disease and procedure type was performed to identify risk factors and model the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score. A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index (CCI), the age-adjusted CCI (aCCI), the ALPPS risk score before Stage 1 (ALPPS-RS1) and Stage 2 (ALPPS-RS2). The model was internally validated applying bootstrapping. Results: A total of 451 patients were included. Mortality was 14.4%. The CAPRA score is calculated based on the following formula: (0.1 × age) - (2 × BSA) + 1 (in the presence of primary liver tumor) + 1 (in the presence of severe cardiovascular disease) + 2 (in the presence of moderate or severe diabetes) + 2 (in the presence of renal disease) + 2 (if classic ALPPS is planned). The predictive ability was 0.837 for the CAPRA score, 0.443 for CCI, 0.519 for aCCI, 0.693 for ALPPS-RS1 and 0.807 for ALPPS-RS2. After 1,000 cycles of bootstrapping the C statistic was 0.793. The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70. Conclusions: Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure. By assessing the patient's preoperative condition in relation to ALPPS, the CAPRA score has a very good ability to predict postoperative mortality.

Left renal vein graft and in situ hepatic perfusion in hepatectomy for complete tumor invasion of hepatic veins: hemodynamic optimization and surgical technique.

PURPOSE: Assessing hepatic vein reconstruction using a left renal vein graft and in situ hypothermic liver perfusion in an extended liver resection. METHODS: Patients included in this study were those with liver tumors undergoing curative surgery with resection and reconstruction of hepatic veins. Hepatic vein was reconstructed using a left renal vein graft. We describe the technical aspects of liver resection and vascular reconstruction, the key aspects of hemodynamic management, and the use of in situ hypothermic liver preservations during liver transection (prior to and during vascular clamping). RESULTS: The right hepatic vein was reconstructed with a median left renal venal graft length of 4.5 cm (IQR, 3.1-5.2). Creatinine levels remained within normal limits in the immediate postoperative phase and during follow-up. Median blood loss was 500 ml (IQR, 300-1500) and in situ perfusion with cold ischemia was 67 min (IQR, 60.5-77.5). The grafts remained patent during the follow-up with no signs of thrombosis. No major postoperative complications were observed. CONCLUSION: Left renal vein graft for the reconstruction of a hepatic vein and in situ hypothermic liver perfusion are feasible during extended liver resection.

Pure laparoscopic vs. hand-assisted liver surgery for segments 7 and 8: propensity score matching analysis.

BACKGROUND: Laparoscopic liver resection of tumors located in segments 7 and 8 are considered a complex resection. The aim of this study was to compare the intraoperative and early postoperative outcomes of patients operated by pure laparoscopic (PLS) vs hand-assisted laparoscopic surgery (HALS). METHODS: From January 2003 to January 2021, we included patients with minimally invasive surgery for lesions located in segments 7 and 8. To overcome selection bias, we performed 1:1 propensity score matching (PSM) between HALS and PLS cohorts, including 30 patients in each of the groups. Of the 60 patients who underwent PSM, we compared the first 30 patients with the following 30 patients. RESULTS: A total of 79 LLRs were performed, 46 by HALS and 33 by PLS. After PSM, in the PLS cohort, cirrhosis was more frequent (33.3% vs. 13.3%, p = 0.02). The surgical time, blood loss, Pringle maneuver, clamping time, and morbidity were similar between both groups, but with a lower hospital stay in the PLS group (3 days vs. 4 days, p < 0.01). In the first 30 patients who underwent LLR, the use of PLS was lower than the use of HALS, increasing due to the learning curve (16.7% in the first period vs. 83.3% in the second period; p < 0.01). The hospital stay was lower in the second period due to the more frequent use of PLS (3 vs. 4 days, p < 0.01). CONCLUSION: PLS presents similar intraoperative and early postoperative results with lower hospital stay for lesions located in segments 7 and 8 compared to HALS. In centers with experience in LLRs, PLS could be performed safely in these segments.