Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

Robotic and laparoscopic right lobe living donation compared to the open approach: A multicenter study on 1194 donor hepatectomies.

Due to the success of minimally invasive liver surgery, laparoscopic and robotic minimally invasive donor hepatectomies (MIDH) are increasingly performed worldwide. We conducted a retrospective, multicentre, propensity score-matched analysis on right lobe MIDH by comparing the robotic, laparoscopic, and open approaches to assess the feasibility, safety, and early outcomes of MIDHs. From January 2016 until December 2020, 1194 donors underwent a right donor hepatectomy performed with a robotic (n = 92), laparoscopic (n = 306), and open approach (n = 796) at 6 high-volume centers. Donor and recipients were matched for different variables using propensity score matching (1:1:2). Donor outcomes were recorded, and postoperative pain was measured through a visual analog scale. Recipients' outcomes were also analyzed. Ninety-two donors undergoing robotic surgery were matched and compared to 92 and 184 donors undergoing laparoscopic and open surgery, respectively. Conversions to open surgery occurred during 1 (1.1%) robotic and 2 (2.2%) laparoscopic procedures. Robotic procedures had a longer operative time (493 ± 96 min) compared to laparoscopic and open procedures (347 ± 120 and 358 ± 95 min; p < 0.001) but were associated with reduced donor blood losses ( p < 0.001). No differences were observed in overall and major complications (≥ IIIa). Robotic hepatectomy donors had significantly less pain compared to the 2 other groups ( p < 0.001). Fifty recipients of robotic-procured grafts were matched to 50 and 100 recipients of laparoscopic and open surgery procured grafts, respectively. No differences were observed in terms of postoperative complications, and recipients' survival was similar ( p =0.455). In very few high-volume centers, robotic right lobe procurement has shown to be a safe procedure. Despite an increased operative and the first warm ischemia times, this approach is associated with reduced intraoperative blood losses and pain compared to the laparoscopic and open approaches. Further data are needed to confirm it as a valuable option for the laparoscopic approach in MIDH.

Multiregional analysis of combined hepatocellular-cholangiocarcinoma reveals histologic diversity and molecular clonality.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of liver tumour that exhibits both hepatocytic and biliary differentiation within the same tumour. The histology and genomic alterations of recurrent/metastatic cHCC-CC are poorly understood. We selected six patients with cHCC-CC whose recurrent or metastatic tumours were histologically confirmed. Four patients with classic cHCC-CCs and two with intermediate cell carcinomas (ICs) were included. The clinicopathological features were evaluated, and next-generation sequencing was performed in 17 multiregional and longitudinal tumour samples. The histology of recurrent/metastatic lesions of classic cHCC-CCs was variable: hepatocellular carcinoma (HCC) was observed in one (25.0%) patient, cHCC-CC in one (25.0%) patient, and cholangiocarcinoma (CC) in two (50.0%) patients. Among 13 samples from four classic cHCC-CC patients, the most frequent pathological variants were TP53 (46.2%), TERT promoter (38.5%), ARID1A mutations (23.1%), and MET amplification (30.8%). In the sequencing analysis of each HCC and CC component, three (75.0%) of the four classic cHCC-CCs shared pathogenic variants. A large proportion of mutations, both pathogenic and those of undetermined significance, were shared by each HCC and CC component. Regarding ICs, the ATM mutation was detected in one patient. In conclusion, the histology of recurrent/metastatic cHCC-CCs was heterogeneous. Genomic profiling of classic cHCC-CCs revealed similar genomic alterations to those of HCC. Considerable overlapping genomic alterations in each HCC and CC component were observed, suggesting a monoclonal origin. Genetic alterations in ICs were different from those in either HCC or CC, suggesting the distinct nature of this tumour.

Microscopic tumor mapping of post-neoadjuvant therapy pancreatic cancer specimens to predict post-surgical recurrence: A prospective cohort study.

BACKGROUND: Although various pathological grading systems are available for evaluating the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant therapy (NAT), their prognostic value has not been thoroughly validated. This study examined whether microscopic tumor mapping of post-NAT specimens could predict tumor recurrence. METHODS: This prospective study enrolled 52 patients who underwent pancreaticoduodenectomy after NAT for PDAC between 2019 and 2021. Microscopic mapping was performed to identify residual tumor loci within the tumor bed using 4 mm2 pixels. Patients were divided into small extent (SE; n = 26) and large extent (LE; n = 26) groups using a cutoff value of 226 mm2. The diagnostic performance for predicting tumor recurrence was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Carbohydrate antigen 19-9 levels were normalised after NAT in more patients in the SE group (SE 21 [80.8%] vs. LE 13 [50.0%]; P = 0.041). Tumor size (P < 0.001), T stage (P < 0.001), positive lymph node yield (P = 0.024), and perineural invasion rate (P = 0.018) were significantly greater in the LE group. The 3-year disease-free survival rate was significantly lower in the LE group (SE 83.3% vs. LE 50.0%, P = 0.004). The area under the ROC curve for mapping extent was 0.743, which was greater than that of the other tumor response scoring systems. CONCLUSIONS: Microscopic tumor mapping of the residual tumor in post-NAT specimens is a significant predictor of post-surgical recurrence, and offers better prognostic performance than the current grading systems.

Evolution of laparoscopic liver resection in the last two decades: lessons from 2000 cases at a referral Korean center.

BACKGROUND AND AIMS: Laparoscopic liver resection (LLR) has evolved to become the standard surgical approach in many referral centers worldwide. The aim of this study was to analyze how LLR evolved at a single high-volume referral center since its introduction, more than two decades ago. METHODS: Data from all consecutive LLR between January 2003 and September 2022 at the Seoul National University Bundang Hospital were analyzed. Perioperative outcomes were compared between three time periods, with major technological innovations considered as landmarks: before introduction of laparoscopic-US and CUSA (2003-2006), before (2006-2015) and after (2015-2022) introduction of high-definition scope. RESULTS: During the analyzed time periods the number of technically challenging procedures increased from 39.2 to 61.1% (p < 0.001). The most recent period showed shorter median operation time (from 267.5' to 175', p < 0.001), lower median estimated blood loss (EBL) (from 500 to 300 ml, p < 0.001), lower intraoperative transfusions (from 33.8 to 9.3%, p < 0.001), shorter median postoperative hospital stay (from 12 to 6 days, p < 0.001). The time period, a technical major resection and an underlying liver cirrhosis were found to be the associated with longer operation time (p < 0.001) in the multivariable linear regression analysis, while tumor size, technically major surgeries and liver cirrhosis were associated with higher EBL (p < 0.001). CONCLUSION: During the last two decades, the indications for patients undergoing LLR have expanded significantly, including more and more challenging procedures and frail patients. Despite such challenges, perioperative outcomes improved, although technically major procedures, cirrhotic patients and huge tumors have still to be considered challenging situations.

A Prospective Analysis of the Effects of a Powder-Type Hemostatic Agent on the Short-Term Outcomes after Liver Resection.

Background and Objectives: Postoperative bleeding is a significant cause of morbidity and mortality following liver resection. Therefore, it is crucial to minimize bleeding during liver resection and effectively manage it when it occurs. Arista® AH (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) is a microporous polysaccharide hemosphere (MPH), a new plant-derived polysaccharide powder hemostat that can be applied to the entire surgical field. This study prospectively assessed the effectiveness of Arista for bleeding control when applied intraoperatively to the liver resection surface. Materials and Methods: Data were collected at Seoul National University Bundang Hospital for patients who underwent liver resection owing to malignant hepatocellular carcinoma or benign liver diseases. We compared the outcomes between 45 patients managed with Arista® AH (data were prospectively collected between September 2022 and May 2023) and 156 patients managed without the use of Arista® AH (data were retrospectively collected between January 2021 and December 2021). Results: There were no significant differences in patient characteristics between the two groups. The estimated blood loss (EBL) was significantly lower in the Arista® AH group compared with the control group (495.56 ± 672.7 mL vs. 691.9 ± 777.5 mL, p = 0.049). The mean postoperative hospital stay was significantly shorter in the Arista® AH group (5.93 ± 1.88 days vs. 6.94 ± 4.17 days, p = 0.024). The time to Jackson-Pratt drain removal was also significantly shorter in the Arista® AH group (4.64 ± 1.31 days vs. 5.30 ± 2.87 days, p = 0.030). The patient subgroup was divided into four categories based on the type of resection and the presence or absence of cirrhosis. Within the subgroup of major resections in non-cirrhotic patients, the Arista® AH group demonstrated significantly better outcomes compared to the control group, showed lower EBL, reduced need for blood transfusions, decreased volume of drain fluid collected within 48 h, earlier removal of drains, and shorter hospital stays. In contrast, for the other subgroups such as minor resection (both non-cirrhotic and cirrhotic) and major resection with cirrhosis, the differences between the Arista® AH and control groups in various parameters like EBL, blood transfusion rates, drain fluid volume, time to drain removal, and duration of hospital stay were not statistically significant. Conclusions: Arista® AH significantly improved intraoperative blood management and postoperative recovery in patients undergoing liver resection, particularly in non-cirrhotic patients who underwent major resection.

Laparoscopic anatomic vs. nonanatomic liver resection for large hepatocellular carcinoma (≥5 cm) in the right lobe.

OBJECTIVE: To determine the impacts and outcomes of laparoscopic anatomic liver resection (LAR) and laparoscopic nonanatomic resection (LNAR) in patients with large hepatocellular carcinoma (HCC) in the right lobe of the liver. BACKGROUND: There are few comparative studies of LAR and LNAR for large HCC. METHOD: Three hundred thirty-seven patients underwent liver resection for large HCC (≥5 cm) at Seoul National University Bundang Hospital, Seoul, Korea, between January 2004 and December 2022. After the exclusion of patients treated with open hepatic resection and those who had left-lobe or bilobar tumors, 94 patients were ultimately included. Patients were divided into LAR group (61 patients) and LNAR group (33 patients). After propensity score matching (PSM) with 1:1 matching, 31 patients were included in each group. The outcomes in the two groups were compared. RESULTS: LAR group had longer operative time than LNAR group (333.7 ± 113.7 vs 210 ± 117.6 min, respectively, P < 0.001), wider safety margin (1.4 ± 1.5 vs 0.7 ± 0.7 cm, respectively, P = 0.015), and lower incidence of recurrence (25.8% vs. 54.8%, respectively, P = 0.021). CONCLUSION: LAR required longer operative time, achieved wider safety margin, and had lower incidence of recurrence than LNAR.

Prognostic Effect of Liver Resection in Extended Cholecystectomy for T2 Gallbladder Cancer Revisited: A Retrospective Cohort Study With Propensity Score-matched Analysis.

OBJECTIVE: This study aimed to evaluate the effect of liver resection on the prognosis of T2 gallbladder cancer (GBC). BACKGROUND: Although extended cholecystectomy [lymph node dissection (LND) + liver resection] is recommended for T2 GBC, recent studies have shown that liver resection does not improve survival outcomes relative to LND alone. METHODS: Patients with pT2 GBC who underwent extended cholecystectomy as an initial procedure and did not reoperation after cholecystectomy at 3 tertiary referral hospitals between January 2010 and December 2020 were analyzed. Extended cholecystectomy was defined as either LND with liver resection (LND+L group) or LND only (LND group). We conducted 2:1 propensity score matching to compare the survival outcomes of the groups. RESULTS: Of the 197 patients enrolled, 100 patients from the LND+L group and 50 from the LND group were successfully matched. The LND+L group experienced greater estimated blood loss ( P <0.001) and a longer postoperative hospital stay ( P =0.047). There was no significant difference in the 5-year disease-free survival (DFS) of the 2 groups (82.7% vs 77.9%, respectively, P =0.376). A subgroup analysis showed that the 5-year DFS was similar in the 2 groups in both T substages (T2a: 77.8% vs 81.8%, respectively, P =0.988; T2b: 88.1% vs 71.5%, respectively, P =0.196). In a multivariable analysis, lymph node metastasis [hazard ratio (HR) 4.80, P =0.006] and perineural invasion (HR 2.61, P =0.047) were independent risk factors for DFS; liver resection was not a prognostic factor (HR 0.68, P =0.381). CONCLUSIONS: Extended cholecystectomy including LND without liver resection may be a reasonable treatment option for selected T2 GBC patients.

Donor Safety and Risk Factors of Pure Laparoscopic Living Donor Right Hepatectomy: A Korean Multicenter Study.

OBJECTIVE: The aim of this study was to identify safety and risk factors of living donor after pure laparoscopic donor right hepatectomy in a Korean multicenter cohort study. BACKGROUND: Pure laparoscopic donor right hepatectomy is not yet a standardized surgical procedure due to lack of data. METHODS: This retrospective study included 543 patients undergoing PLRDH between 2010 and 2018 in 5 Korean transplantation centers. Complication rates were assessed and multivariate logistic regression analyses were performed to identify risk factors of open conversion, overall complications, major complications, and biliary complications. RESULTS: Regarding open conversion, the incidence was 1.7% and the risk factor was body mass index >30 kg/m 2 [ P =0.001, odds ratio (OR)=22.72, 95% CI=3.56-146.39]. Rates of overall, major (Clavien-Dindo classification III-IV), and biliary complications were 9.2%, 4.4%, and 3.5%, respectively. For overall complications, risk factors were graft weight >700 g ( P =0.007, OR=2.66, 95% CI=1.31-5.41), estimated blood loss ( P <0.001, OR=4.84, 95% CI=2.50-9.38), and operation time >400 minutes ( P =0.01, OR=2.46, 95% CI=1.25-4.88). For major complications, risk factors were graft weight >700 g ( P =0.002, OR=4.01, 95% CI=1.67-9.62) and operation time >400 minutes ( P =0.003, OR=3.84, 95% CI=1.60-9.21). For biliary complications, risk factors were graft weight >700 g ( P =0.01, OR=4.34, 95% CI=1.40-13.45) and operation time >400 minutes ( P =0.01, OR=4.16, 95% CI=1.34-12.88). CONCLUSION: Careful donor selection for PLRDH considering body mass index, graft weight, estimated blood loss, and operation time combined with skilled procedure can improve donor safety.

Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer: A Multicenter Study.

OBJECTIVE: The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.

Defining Global Benchmarks for Laparoscopic Liver Resections: An International Multicenter Study.

OBJECTIVE: To establish global benchmark outcomes indicators after laparoscopic liver resections (L-LR). BACKGROUND: There is limited published data to date on the best achievable outcomes after L-LR. METHODS: This is a post hoc analysis of a multicenter database of 11,983 patients undergoing L-LR in 45 international centers in 4 continents between 2015 and 2020. Three specific procedures: left lateral sectionectomy (LLS), left hepatectomy (LH), and right hepatectomy (RH) were selected to represent the 3 difficulty levels of L-LR. Fifteen outcome indicators were selected to establish benchmark cutoffs. RESULTS: There were 3519 L-LR (LLS, LH, RH) of which 1258 L-LR (40.6%) cases performed in 34 benchmark expert centers qualified as low-risk benchmark cases. These included 659 LLS (52.4%), 306 LH (24.3%), and 293 RH (23.3%). The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, and 90-day mortality after LLS, LH, and RH were 209.5, 302, and 426 minutes; 2.1%, 13.4%, and 13.0%; 3.2%, 20%, and 47.1%; 0%, 7.1%, and 10.5%; 11.1%, 20%, and 50%; 0%, 7.1%, and 20%; and 0%, 0%, and 0%, respectively. CONCLUSIONS: This study established the first global benchmark outcomes for L-LR in a large-scale international patient cohort. It provides an up-to-date reference regarding the "best achievable" results for L-LR for which centers adopting L-LR can use as a comparison to enable an objective assessment of performance gaps and learning curves.

An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS).

OBJECTIVE: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. BACKGROUND: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. METHODS: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. RESULTS: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. CONCLUSIONS: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

Machine learning improves the accuracy of graft weight prediction in living donor liver transplantation.

Precise graft weight (GW) estimation is essential for planning living donor liver transplantation to select grafts of adequate size for the recipient. This study aimed to investigate whether a machine-learning model can improve the accuracy of GW estimation. Data from 872 consecutive living donors of a left lateral sector, left lobe, or right lobe to adults or children for living-related liver transplantation were collected from January 2011 to December 2019. Supervised machine-learning models were trained (80% of observations) to predict GW using the following information: donor's age, sex, height, weight, and body mass index; graft type (left, right, or left lateral lobe); computed tomography estimated graft volume and total liver volume. Model performance was measured in a random independent set (20% of observations) and in an external validation cohort using the mean absolute error (MAE) and the mean absolute percentage error and compared with methods currently available for GW estimation. The best-performing machine-learning model showed an MAE value of 50 ± 62 g in predicting GW, with a mean error of 10.3%. These errors were significantly lower than those observed with alternative methods. In addition, 62% of predictions had errors <10%, whereas errors >15% were observed in only 18.4% of the cases compared with the 34.6% of the predictions obtained with the best alternative method ( p < 0.001). The machine-learning model is made available as a web application ( http://graftweight.shinyapps.io/prediction ). Machine learning can improve the precision of GW estimation compared with currently available methods by reducing the frequency of significant errors. The coupling of anthropometric variables to the preoperatively estimated graft volume seems necessary to improve the accuracy of GW estimation.

Validation of the Anatomical and Biological Definitions of Borderline Resectable Pancreatic Cancer According to the 2017 International Consensus for Survival and Recurrence in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Upfront Surgery.

BACKGROUND: The International Consensus Criteria (ICC) (2017) redefined patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) according to anatomical, biological, and conditional aspects. However, these new criteria have not been validated comprehensively. The aim of this retrospective cohort study was to validate the anatomical and biological definitions of BR-PDAC for oncological outcomes in patients with resectable (R) and BR-PDAC undergoing upfront surgery. METHODS: A total of 404 patients who underwent upfront surgery for R- and BR-PDAC from 2004 to 2020 were included. The patients were classified according to the ICC as follows: resectable (R) (n = 259), anatomical borderline (BR-A) (n = 43), biological borderline (BR-B) (n = 81), and anatomical and biologic borderline (BR-AB) (n = 21). RESULTS: Compared with the R and BR-B groups, the BR-A and BR-AB groups had higher postoperative complication rates (16.5% and 27.2% vs 32.5% and 33.4%; P < 0.001) and significantly lower R0 resection rates (85.7% and 80.2% vs 65.1% and 61.9%; P = 0.003). In contrast, compared with the R and BR-A groups, the BR-B (32.1%) and BR-AB (57.1%) groups had higher early recurrence rates (within postoperative 6 months) (16.5% and 25.6% vs 32.1% and 57.1%; P < 0.001) and significantly lower 3-year recurrence-free survival rates (36.1% and 20.7% vs 12.1% and 7.8%; P < 0.001). CONCLUSION: Anatomically defined BR-PDAC was associated with a higher risk of margin-positive resection and postoperative complication rates, while biologically defined BR-PDAC was associated with higher early recurrence rates and lower survival rates. Thus, the anatomical and biological definitions are useful in predicting the prognosis and determining the usefulness of neoadjuvant therapy.

An aptamer-based magnetic resonance imaging contrast agent for detecting oligomeric amyloid-ß in the brain of an Alzheimer's disease mouse model.

The oligomeric amyloid-ß (oAß) is a reliable feature for an early diagnosis of Alzheimer's disease (AD). Therefore, the objective of this study was to demonstrate imaging of oAß deposits using our developed DNA aptamer called ob5 conjugated with gadolinium (Gd)-dodecane tetraacetic acid (DOTA) as a contrast agent for early diagnosis of AD using MRI. An oAß-specific aptamer was developed by amide bond formation and conjugated to Gd-DOTA MRI contrast agent and/or cyanine5 (cy5). We verified the performance of our new contrast agent with an AD mouse model using in vivo and ex vivo fluorescent imaging and animal MRI experiments. The presence of soluble Aß in 3xTg AD mice was detected using GdDOTA-ob5-cy5 probe ex vivo. Fluorescence intensities of the GdDOTA-ob5-cy5 contrast agent were high in the brains of 3xTg-AD mice, but relatively low in the brains of control mice. The GdDOTA-ob5 contrast agent had higher relaxivity than a clinically available contrast agent. T1-weighted MRI signals in 5-month-old 3xTg AD mice increased at 5 min, were prolonged until 10 min, then decreased 15 min after injecting the GdDOTA-ob5 contrast agent. Our targeted DNA aptamer GdDOTA-ob5 contrast agent could be potentially useful for validating the efficacy of a novel diagnostic contrast agent for selectively targeting neurotoxic oAß. It could ultimately be used for early diagnosis of AD.

Laparoscopic versus open hepatectomy for large hepatocellular carcinoma: a single center propensity-score-matching comparative analysis of perioperative outcomes and long-term survival.

BACKGROUND: Although the benefits of laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC) in most circumstances are evident, the benefits for large HCC are contentious. This study aimed to compare the perioperative outcomes and survival after LH versus open hepatectomy (OH) in large HCC patients. METHODS: An analysis of prospectively maintained database included 215 hepatectomies for large HCC (diameter ≥ 5 cm). The operative and survival outcomes were compared between the LH group (n = 109) and the OH group (n = 106). Propensity score matching (PSM) 1:1 included 70 patients in each group. The entire cohort multivariable analyses were performed to identify the factors associated with surgical complications and suboptimal recurrence-free survival (RFS). RESULTS: After PSM, baseline characteristics and the extent of liver resection were similar in both groups. The LH group had a shorter hospital stay than the OH group (7 vs 9.5 days, p = 0.001). The R0 resection rate, complication rate, overall survival, and RFS were similar between the groups. The multivariate analyses revealed two independent factors predicting surgical complication (major resection; p < 0.001 and large volume blood loss; p = 0.042), and 3 independent factors predicting suboptimal RFS including R1 resection (p = 0.011), multifocal HCC (p = 0.005), and microvascular invasion (p = 0.001). LH was not associated with surgical complication and suboptimal RFS. CONCLUSION: Our study highlights the benefits of LH by improving the perioperative outcomes, without long-term survival inferiority in selected large HCC patients compared with conventional OH. LH can be an attractive option for large HCC treatment.

Validation of original, alternative, and updated alternative fistula risk scores after open and minimally invasive pancreatoduodenectomy in an Asian patient cohort.

BACKGROUND: This study aimed to validate and compare the performance of the original fistula risk scores (o-FRS), alternative (a-FRS), and updated alternative FRS (ua-FRS) after open pancreatoduodenectomy (OPD) and laparoscopic pancreatoduodenectomy (LPD) in an Asian patient cohort. METHODS: Data of 597 consecutive patients who underwent PD (305 OPD, 274 LPD) were collected from two tertiary centers. Model performance was assessed using the area under the receiver operating curve (AUC). RESULTS: The overall AUC values of o-FRS, a-FRS, and ua-FRS were 0.67, 0.69, and 0.68, respectively, which were lower than those of the Western validation. Three FRS systems had similar AUC values in the overall and OPD groups, whereas ua-FRS had a higher AUC than o-FRS in the LPD group. The accuracy of ua-FRS (47.2%) was higher than that of o-FRS (39.0%) and a-FRS (19.5%) overall, but low specificity and low positive predictive value were observed regardless of the operative type across the three FRS systems. In the multivariate analysis, pathology, estimated blood loss, and body mass index were not independent risk factors for CR-POPF in the OPD and LPD groups. CONCLUSIONS: Current FRS systems have some limitations, including a relatively lower performance in an Asian cohort, low positive predictive values, and inclusion of insignificant risk factors.

Propensity score-matched analysis of laparoscopic-assisted and hand-assisted laparoscopic liver resection versus pure laparoscopic liver resection: an international multicenter study.

BACKGROUND: Laparoscopic-assisted (LALR) and hand-assisted (HALR) liver resections have been utilized during the early adoption phase by surgeons when transitioning from open surgery to pure LLR. To date, there are limited data reporting on the outcomes of LALR or HALR compared to LLR. The objective was to compare the perioperative outcomes after LALR and HALR versus pure LLR. METHODS: This is an international multicentric analysis of 6609 patients undergoing minimal-invasive liver resection at 21 centers between 2004 and 2019. Perioperative outcomes were analyzed after propensity score matching (PSM) comparison between LALR and HALR versus LLR. RESULTS: 5279 cases met study criteria of whom 5033 underwent LLR (95.3%), 146 underwent LALR (2.8%) and 100 underwent HALR (1.9%). After 1:4 PSM, LALR was associated with inferior outcomes as evidenced by the longer postoperative stay, higher readmission rate, higher major morbidity rate and higher in-hospital mortality rate. Similarly, 1:6 PSM comparison between HALR and LLR also demonstrated poorer outcomes associated with HALR as demonstrated by the higher open conversion rate and higher blood transfusion rate. All 3 approaches technical variants demonstrated the same oncological radicality (R1 rate). CONCLUSION: LALR and HALR performed during the learning curve was associated with inferior perioperative outcomes compared to pure LLR.

An international multicentre propensity score matched analysis comparing between robotic versus laparoscopic left lateral sectionectomy.

BACKGROUND: Left lateral sectionectomy (LLS) is one of the most commonly performed minimally invasive liver resections. While laparoscopic (L)-LLS is a well-established technique, over traditional open resection, it remains controversial if robotic (R)-LLS provides any advantages of L-LLS. METHODS: A post hoc analysis of 997 patients from 21 international centres undergoing L-LLS or R-LLS from 2006 to 2020 was conducted. A total of 886 cases (214 R-LLS, 672 L-LLS) met study criteria. 1:1 and 1:2 propensity score matched (PSM) comparison was performed between R-LLS & L-LLS. Further subset analysis by Iwate difficulty was also performed. Outcomes measured include operating time, blood loss, open conversion, readmission rates, morbidity and mortality. RESULTS: Comparison between R-LLS and L-LLS after PSM 1:2 demonstrated statistically significantly lower open conversion rate in R-LLS than L-LLS (0.6% versus 5%, p = 0.009) and median blood loss was also statistically significantly lower in R-LLS at 50 (80) versus 100 (170) in L-LLS (p = 0.011) after PSM 1:1 although there was no difference in the blood transfusion rate. Pringle manoeuvre was also found to be used more frequently in R-LLS, with 53(24.8%) cases versus to 84(12.5%) L-LLS cases (p < 0.001). There was no significant difference in the other key perioperative outcomes such as operating time, length of stay, postoperative morbidity, major morbidity and 90-day mortality between both groups. CONCLUSION: R-LLS was associated with similar key perioperative outcomes compared to L-LLS. It was also associated with significantly lower blood loss and open conversion rates compared to L-LLS.

Robotic versus laparoscopic liver resections for hepatolithiasis: an international multicenter propensity score matched analysis.

INTRODUCTION: Minimally invasive liver resection (MILR) is widely recognized as a safe and beneficial procedure in the treatment of both malignant and benign liver diseases. Hepatolithiasis has traditionally been reported to be endemic only in East Asia, but has seen a worldwide uptrend in recent decades with increasingly frequent and invasive endoscopic instrumentation of the biliary tract for a myriad of conditions. To date, there has been a woeful lack of high-quality evidence comparing the laparoscopic (LLR) and robotic (RLR) approaches to treatment hepatolithiasis. METHODS: This is an international multicenter retrospective analysis of 273 patients who underwent RLR or LRR for hepatolithiasis at 33 centers in 2003-2020. The baseline clinicopathological characteristics and perioperative outcomes of these patients were assessed. To minimize selection bias, 1:1 (48 and 48 cases of RLR and LLR, respectively) and 1:2 (37 and 74 cases of RLR and LLR, respectively) propensity score matching (PSM) was performed. RESULTS: In the unmatched cohort, 63 (23.1%) patients underwent RLR, and 210 (76.9%) patients underwent LLR. Patient clinicopathological characteristics were comparable between the groups after PSM. After 1:1 and 1:2 PSM, RLR was associated with less blood loss (p = 0.003 in 1:2 PSM; p = 0.005 in 1:1 PSM), less patients with blood loss greater than 300 ml (p = 0.024 in 1:2 PSM; p = 0.027 in 1:1 PSM), and lower conversion rate to open surgery (p = 0.003 in 1:2 PSM; p < 0.001 in 1:1 PSM). There was no significant difference between RLR and LLR in use of the Pringle maneuver, median Pringle maneuver duration, 30-day readmission rate, postoperative morbidity, major morbidity, reoperation, and mortality. CONCLUSION: Both RLR and LLR were safe and feasible for hepatolithiasis. RLR was associated with significantly less blood loss and lower open conversion rate.