BACKGROUND:Minimally invasive surgical techniques have been widely adopted in colorectal surgery. New technological breakthroughs have led to even less invasive alternatives like single-port surgery, but this has been hindered by technical challenges such as the collision of robotic arms within a limited space. The Intuitive da Vinci Single-Port robotic platform is a novel system that overcomes some of these challenges. IMPACT OF INNOVATION:This study aimed to assess the safety and feasibility of the Intuitive da Vinci Single-Port robotic platform in right segmental colectomies among adult patients. These findings may set the stage for more widespread use of single-port robotic surgery. TECHNOLOGY, MATERIALS, AND METHODS:The Intuitive da Vinci Single-Port robot is a system designed specifically for single-port robotic surgery. This platform enables flexible port location and efficient internal and external range of motion using a single C-shaped arm. In the present study, right colectomies were performed in adult patients using this platform between May 2022 and November 2022, and they were compared to right colectomies in adult patients performed using the standard multiport platform between January 2019 and December 2022. The main outcome measure was safety and quality event rates. PRELIMINARY RESULTS:Of 30 patients, 16.7% of patients (n = 5) underwent single-port robotic right colectomy and 83.3% (n = 25) underwent multiport right colectomy. In the single-port group, 40% of patients (n = 2) developed a safety/quality event (postoperative portal vein thrombosis and excessive postoperative pain). In the multiport group, 32% of patients (n = 8) developed 1 safety/quality event and 8% (n = 2) had more than 1 event. CONCLUSIONS AND FUTURE DIRECTIONS:This preliminary study, one of the first Food and Drug Administration-approved, investigator-initiated uses of this platform in colorectal surgeries, shows that this platform is a safe and feasible option for right colectomies. On preliminary evaluation, it appears comparable in terms of relevant safety/quality events to the multiport platform. CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov NCT05321134.

BACKGROUND:Pancreatic cancer is the third leading cause of cancer-related death in the United States, with surgical resection being the only option for long-term survival. The ability to manage vascular involvement has expanded the pool of patients who are able to undergo resection with curative intent. However, not all vascular involvements can be detected preoperatively. This study aimed to investigate the patterns of vascular resection and methods of repair or reconstruction METHODS: This was a single-center retrospective review of adult patients undergoing pancreatectomy with vascular involvement at a tertiary care referral hospital between 2010 and 2022. The primary endpoint was graft thrombosis within 90 days. RESULTS:A total of 147 patients were included in the study. Of note, 21.8% of patients were not suspected of having vascular involvement preoperatively. Moreover, 68.0% of patients required vascular reconstruction, whereas the remaining 32.0% of patients underwent repair (either primary repair or patch angioplasty). Most patients who underwent reconstruction underwent primary end-to-end anastomosis (63.0%), with 19 patients requiring autologous interposition grafts and 16 patients requiring CryoVein interposition grafts. Univariate analysis found no clinical or technical predictors of early or 90-day thrombosis, including graft choice. In addition, 30- and 90-day mortalities occurred in 1 and 7 patients, respectively. CONCLUSION:Pancreatectomy with vascular resection can be performed with low mortality in carefully selected patients. Unsuspected vascular involvement is relatively common (1 in 5). If autologous graft is not readily available, CryoVein is a safe alternative with similar perioperative outcomes.

Background: Hepatic artery infusion (HAI) pumps are utilized in the multimodality treatment of advanced colorectal liver metastases (CRLM) and intra-hepatic cholangiocarcinoma. During surgical implantation, dye is routinely administered into the gastroduodenal artery (GDA) catheter to confirm appropriate hepatic perfusion and a lack of extrahepatic perfusion. The historical standard of care has been administration of methylene blue dye through the catheter. There are potential advantages to other dyes, however, and our center favors indocyanine green (ICG) for this purpose. The video demonstrates multiple surgical cases demonstrating the utility of this approach intraoperatively.

Background and aimsMetabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study aims to investigate the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed.MethodsBetween 2001 and 2021, data from 24 centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death due to tumor progression was the primary endpoint whereas deaths with recurrence due to other causes were considered as competing events.Results813 patients were included. Median OS was 81.4 months (28.1-157.0), and recurrence occurred in 48.3% of patients with a median RFS of 39.8 months (15.7-174.7). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p=0.001). Size >5cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (HR 0.985, 95%CI: 0.977, 0.995; p=0.002).ConclusionsPatients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common cause of cancer-related death worldwide [...].

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Objective: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). Background: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. Material and Methods: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. Results: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P=0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P=0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P=0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P=0.015), posthepatectomy liver failure (0.6% vs 4.3%, P=0.008), and bile leaks (2.2% vs 6.4%, P=0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P=0.002) and day 3 (3.1% vs 11.4%, P<0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P<0.001). There was no significant difference in overall survival and disease-free survival. Conclusions: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Background: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. Aims: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. Materials and Methods: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. Results: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%–78.2%) (https://childb.shinyapps.io/NomogramMajorMorbidity90days/). Conclusions: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Objective: To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)” and 90-day mortality. Summary of Background Data: PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF. Methods: Adults who underwent major hepatectomies at twelve international centers (2010–2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades. Results: Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2–7.2; grade C OR 137.0; 95% CI: 59.2–317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6–232.1). Grade A was not associated with CCI> 40 or 90-day mortality. Conclusions: In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

Background: Given increased effectiveness and adoption of neoadjuvant chemotherapy (NAT) for pancreatic adenocarcinoma (PDAC), there has been increased willingness to explore borderline and locally advanced patients for resection that may include venous and/or arterial resection. We hypothesized that with careful patient selection, and a team approach including transplant surgery and vascular surgery, perioperative outcomes would be comparable to reported outcomes. The aim of the study was to examine our recent indications and outcomes for pancreatectomy with vascular resection.

Background:Optimal therapy for stage II colon cancer remains unclear, and national guidelines recommend "consideration" of adjuvant chemotherapy (ACT) in the presence of high-risk features, including inadequate lymph node yield (LNY, <12 nodes). This study aims to determine whether the survival benefit of ACT in stage II disease varies based on the adequacy of LNY. Methods:We used the National Cancer Database (NCDB) to identify adults who underwent resection for a single primary T3 or T4 colon cancer between 2006 and 2018. Multivariable logistic regression tested for associations between ACT and prespecified demographic and clinical characteristics, including the adequacy of LNY. We used Cox proportional hazards models to assess overall survival and restricted cubic splines to estimate the optimal LNY threshold to dichotomize patients based on overall survival. Results:Unadjusted 5- and 10-year survival rates were 84% and 75%, respectively, among patients who received ACT and 70% and 50% among patients who did not (log-rank P < 0.01). Inadequate LNY was independently associated with both receipt of ACT (odds ratios, 1.50; P < 0.01) and decreased overall survival [hazard ratio (HR), 1.56; P < 0.01]. ACT was independently associated with improved survival (HR, 0.67; P < 0.01); this effect size did not change based on the adequacy of LNY (interaction P = 0.41). Results were robust to re-analysis with our cohort-optimized threshold of 18 lymph nodes. Conclusions:Consistent with contemporary guidelines, patients with inadequate LNY are more likely to receive ACT. LNY adequacy is an independent prognostic factor but, in isolation, should not dictate whether patients receive ACT.

Pediatric hepatoblastoma is the most common primary liver cancer in infants and children. Studies of hepatoblastoma that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, hepatoblastoma tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we use single-cell transcriptomic techniques to analyze resected human pediatric hepatoblastoma specimens, and identify five hepatoblastoma tumor signatures that may account for the tumor heterogeneity observed in this disease. Notably, patient-derived hepatoblastoma spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. In this work, we define hepatoblastoma tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

Few resources exist for surgical learners in interpreting trends in biochemical markers following major hepatic resections. Adult patients who underwent major hepatectomy between 2010 and 2020 were included from twelve international centers. Patients were classified as healthy donor, benign disease, non-alcoholic fatty liver disease, prior chemotherapy, or cirrhosis. Median values of total bilirubin and INR were plotted against time and compared across groups using the Kruskal–Wallis test. Across groups (n = 989), median total bilirubin and INR were observed to peak on postoperative day (POD) 1. While the healthy donor group (n = 156) had the highest median total bilirubin on POD1 (2.4, IQR: 1.7–3.3), they had the fastest rate of recovery such that by POD5, values were lower than those of the NAFLD (n = 26), chemotherapy (n = 92), and cirrhosis (n = 668) groups. Donor patients also had the highest POD1 INR (median 1.5, IQR: 1.4–1.7), while patients with NAFLD had the highest POD5 INR levels (1.2, IQR: 1.1, 1.4). The lowest POD1 total bilirubin and INR levels were observed in the cirrhosis group (1.5, 1.3, respectively). Statistically significant differences in total bilirubin and INR were observed across groups at all timepoints (p < 0.05). We observed the healthy donor patients to have the highest postoperative enzyme peaks, but most rapid rate of return to normal. This illustration of the postoperative kinetics of biochemical liver function tests may serve as a useful reference for clinical learners monitoring patients in the first week following major hepatectomy.

Introduction Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managing recurrence for patients undergoing LT for HCC.Areas Covered In this review, we will provide an overview of methods of patient risk stratification in the post-transplant period, the data around surveillance for HCC recurrence, and the evidence for and against post-LT adjuvant treatment strategies. Finally, we will provide data regarding treatment options for patients with HCC recurrence after LT. Using an extensive search of original papers and society guidelines, this paper provides a comprehensive review of the data for assessing risk and managing recurrence for patients undergoing LT for HCC.Expert Opinion The development of multiple post-transplant prognostic scoring systems have allowed for improved assessment of recurrence risk and stratification of patients. However, the ability to translate this information into surveillance and therapeutic strategies that improve patient outcomes still have to be fully demonstrated. Post-LT immunosuppression strategies have been implemented in order to attempt to reduce this risk. Evidence-based strategies for managing recurrent HCC are evolving. We expect that with further understanding of individual patient characteristics will allow for optimal therapeutic selection.

Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages. Bevacizumab-resistant patient glioblastomas and both novel xenograft models of resistance had less MIF than bevacizumab-naive tumors, and harbored more M2/protumoral macrophages that specifically localized to the tumor edge. Xenografts expressing MIF-shRNA grew more rapidly with greater angiogenesis and had macrophages localizing to the tumor edge which were more prevalent and proliferative, and displayed M2 polarization, whereas bevacizumab-resistant xenografts transduced to upregulate MIF exhibited the opposite changes. Bone marrow-derived macrophage were polarized to an M2 phenotype in the presence of condition-media derived from bevacizumab-resistant xenograft-derived cells, while recombinant MIF drove M1 polarization. Media from macrophages exposed to bevacizumab-resistant tumor cell conditioned media increased glioma cell proliferation compared with media from macrophages exposed to bevacizumab-responsive tumor cell media, suggesting that macrophage polarization in bevacizumab-resistant xenografts is the source of their aggressive biology and results from a secreted factor. Two mechanisms of bevacizumab-induced MIF reduction were identified: (1) bevacizumab bound MIF and blocked MIF-induced M1 polarization of macrophages; and (2) VEGF increased glioma MIF production in a VEGFR2-dependent manner, suggesting that bevacizumab-induced VEGF depletion would downregulate MIF. Site-directed biopsies revealed enriched MIF and VEGF at the enhancing edge in bevacizumab-naive patients. This MIF enrichment was lost in bevacizumab-resistant glioblastomas, driving a tumor edge M1-to-M2 transition. Thus, bevacizumab resistance is driven by reduced MIF at the tumor edge causing proliferative expansion of M2 macrophages, which in turn promotes tumor growth.

Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders, including ASDs (autism spectrum disorders). In this study, we examined the combinatorial effect of two factors thought to be involved in autism – reduction in the expression of the extracellular matrix protein reelin and prenatal exposure to an organophosphate pesticide, CPO (chlorpyrifos oxon). Mice with reduced reelin expression or prenatal exposure to CPO exhibited subtle changes in ultrasound vocalization, open field behaviour, social interaction and repetitive behaviour. Paradoxically, mice exposed to both variables often exhibited a mitigation of abnormal behaviours, rather than increased behavioural abnormalities as expected. We identified specific differences in males and females in response to both of these variables. In addition to behavioural abnormalities, we identified anatomical alterations in the olfactory bulb, piriform cortex, hippocampus and cerebellum. As with our behavioural studies, anatomical alterations appeared to be ameliorated in the presence of both variables. While these observations support an interaction between loss of reelin expression and CPO exposure, our results suggest a complexity to this interaction beyond an additive effect of individual phenotypes.