Advancing minimally invasive hepato-pancreato-biliary surgery: ensuring safety with implementation.

BACKGROUND: Although minimally invasive hepato-pancreato-biliary (MIS HPB) surgery can be performed with good outcomes, there are currently no standardized requirements for centers or surgeons who wish to implement MIS HPB surgery. The aim of this study was to create a consensus statement regarding safe dissemination and implementation of MIS HPB surgical programs. METHODS: Sixteen key questions regarding safety in MIS HPB surgery were generated after a focused literature search and iterative review by three field experts. Participants for the working group were then selected using sequential purposive sampling and snowball techniques. Review of the 16 questions took place over a single 2-h meeting. The senior author facilitated the session, and a modified nominal group technique was used. RESULTS: Twenty three surgeons were in attendance. All participants agreed or strongly agreed that formal guidelines should exist for both institutions and individual surgeons interested in implementing MIS HPB surgery and that routine monitoring and reporting of institutional and surgeon technical outcomes should be performed. Regarding volume cutoffs, most participants (91%) agreed or strongly agreed that a minimum annual institutional volume cutoff for complex MIS HPB surgery, such as major hepatectomy or pancreaticoduodenectomy, should exist. A smaller proportion (74%) agreed or strongly agreed that a minimum annual surgeon volume requirement should exist. The majority of participants agreed or strongly agreed that surgeons were responsible for defining (100%) and enforcing (78%) guidelines to ensure the overall safety of MIS HPB programs. Finally, formal MIS HPB training, minimum case volume requirements, institutional support and infrastructure, and mandatory collection of outcomes data were all recognized as important aspects of safe implementation of MIS HPB surgery. CONCLUSIONS: Safe implementation of MIS HPB surgery requires a thoughtful process that incorporates structured training, sufficient volume and expertise, a proper institutional ecosystem, and monitoring of outcomes.

Escalated-dose radiotherapy for unresected locally advanced pancreatic cancer: Patterns of care and survival in the United States.

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes. METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 >70 and ≤132 Gy was labeled EDR. We identified associations of EDR and OS using logistic and Cox regressions, respectively. RESULTS: Among the definitive therapy subset (n = 54,115) of the entire study cohort (n = 91,493), the most common treatments were chemotherapy alone (69%), chemotherapy and radiation (29%), and RT alone (2%). For the radiation therapy subset (n = 16,978), use of pancreas-directed RT remained between 13% and 17% over the study period (ptrend > 0.999). Using multivariable logistic regression, treatment at an academic/research facility (adjusted odds ratio [aOR] 1.46, p < 0.001) and treatment between 2016 and 2019 (aOR 2.54, p < 0.001) were associated with greater receipt of EDR, whereas use of chemotherapy (aOR 0.60, p < 0.001) was associated with less receipt. Median OS estimates for EDR and CDR were 14.5 months and 13.0 months (p < 0.0001), respectively. For radiation therapy subset patients with available survival data (n = 13,579), multivariable Cox regression correlated EDR (adjusted hazard ratio 0.85, 95% confidence interval 0.80-0.91; p < 0.001) with longer OS versus CDR. DISCUSSION AND CONCLUSIONS: Utilization of EDR has increased since 2016, but overall utilization of RT for LAPC has remained at less than one in five patients for almost two decades. These real-world results additionally provide an estimate of effect size of EDR for future prospective trials.

Reproducibility and efficiency of liver volumetry using manual method and liver analysis software.

BACKGROUND: For liver volumetry, manual tracing on computed tomography (CT) images is time-consuming and operator dependent. To overcome these disadvantages, several three-dimensional simulation software programs have been developed; however, their efficacy has not fully been evaluated. METHODS: Three physicians performed liver volumetry on preoperative CT images on 30 patients who underwent formal right hepatectomy, using manual tracing volumetry and two simulation software programs, SYNAPSE and syngo.via. The future liver remnant (FLR) was calculated using each method of volumetry. The primary endpoint was reproducibility and secondary outcomes were calculation time and learning curve. RESULTS: The mean FLR was significantly lower for manual volumetry than for SYNAPSE or syngo.via; there was no significant difference in mean FLR between the two software-based methods. Reproducibility was lower for the manual method than for the software-based methods. Mean calculation time was shortest for SYNAPSE. For the two physicians unfamiliar with the software, no obvious learning curve was observed for using SYNAPSE, whereas learning curves were observed for using syngo.via. CONCLUSIONS: Liver volumetry was more reproducible and faster with three-dimensional simulation software, especially SYNAPSE software, than with the conventional manual tracing method. Software can help even inexperienced physicians learn quickly how to perform liver volumetry.

Current Perspectives and Progress in Preoperative Portal Vein Embolization with Stem Cell Augmentation (PVESA).

Portal vein embolization with stem cell augmentation (PVESA) is an emerging approach for enhancing the growth of the liver segment that will remain after surgery (i.e., future liver remnant, FLR) in patients with liver cancer. Conventional portal vein embolization (PVE) aims to induce preoperative FLR growth, but it has a risk of failure in patients with underlying liver dysfunction and comorbid illnesses. PVESA combines PVE with stem cell therapy to potentially improve FLR size and function more effectively and efficiently. Various types of stem cells can help improve liver growth by secreting paracrine signals for hepatocyte growth or by transforming into hepatocytes. Mesenchymal stem cells (MSCs), unrestricted somatic stem cells, and small hepatocyte-like progenitor cells have been used to augment liver growth in preclinical animal models, while clinical studies have demonstrated the benefit of CD133 + bone marrow-derived MSCs and hematopoietic stem cells. These investigations have shown that PVESA is generally safe and enhances liver growth after PVE. However, optimizing the selection, collection, and application of stem cells remains crucial to maximize benefits and minimize risks. Additionally, advanced stem cell technologies, such as priming, genetic modification, and extracellular vesicle-based therapy, that could further enhance efficacy outcomes should be evaluated. Despite its potential, PVESA requires more investigations, particularly mechanistic studies that involve orthotopic animal models of liver cancer with concomitant liver injury as well as larger human trials.

Prevalence of and Factors Associated with Financial Toxicity After Pancreatectomy and Gastrectomy.

BACKGROUND: Financial toxicity (FT) refers to the adverse impact of cancer treatment costs on patients' experiences, potentially leading to poor adherence to treatment and outcomes. However, the prevalence of FT among patients undergoing major upper gastrointestinal cancer operations, as well as factors associated with FT, remain unclear. METHODS: We conducted a cross-sectional study by sending the Comprehensive Score for financial Toxicity (COST) survey and Surgery-Q (a survey specifically developed for this study) to patients who underwent gastrectomy or pancreatectomy for malignant disease at our institution in 2019-2021. RESULTS: We sent the surveys to 627 patients and received responses from 101 (16%) patients. The FT prevalence (COST score <26) was 48 (48%). Patients likely to experience FT were younger than 50 years of age, of non-White race, earned an annual income <$75,000, and had credit scores <740 (all p < 0.05). Additionally, longer hospital stay (p = 0.041), extended time off work for surgery (p = 0.011), and extended time off work for caregivers (p = 0.005) were associated with FT. Procedure type was not associated with FT; however, patients who underwent minimally invasive surgery (MIS) had a lower FT probability (p = 0.042). In a multivariable analysis, age <50 years (p = 0.031) and credit score <740 (p < 0.001) were associated with high FT risk, while MIS was associated with low FT risk (p = 0.024). CONCLUSIONS: Patients with upper gastrointestinal cancer have a major risk of FT. In addition to predicting the FT risk before surgery, facilitating quicker functional recovery with the appropriate use of MIS is considered important to reducing the FT risk.

Revisiting the Malignant Masquerade at the Liver Hilum: Have We Made Progress?

BACKGROUND: Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar obstruction and long-term outcomes after resection. METHODS: Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26 months (range 0-281 months). RESULTS: Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80 U/mL (range 1-5779) and 21 U/mL (range 1-681) among patients with malignant and benign strictures, respectively (p = 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all p < 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3-4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (p = 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (p = non-significant). CONCLUSIONS: Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures.

A Practical Guide to Inflow Control, Retraction, and Exposure for Robotic Hepatectomy.

Establishment of inflow control and gentle effective retraction of the liver for optimal exposure are critical to safe hepatectomy. Multiple methods have been previously reported for inflow control in minimally invasive (MIS) hepatectomy including Huang's Loop.1-3 We describe here the assembly and use of our modified version of Huang's loop that permits adjustable, atraumatic, and totally intracorporeal inflow control. We use a soft 16-French urinary catheter with a single premade opening near the blunt tip, across which a small slit is created. A beveled cut is made to the catheter 12-15 cm from the blunt tip and a suture sewn there that can be grasped to pull this beveled tail through the slit and window around the porta hepatis; this loop can be tightened or loosened with ease. For liver retraction, current techniques can be traumatic, especially when instruments apply traction directly onto the liver.4 Our preferred approach utilizes a liver sling made from a soft, rolled surgical sponge with 15-cm silk ties secured at each end; the length of the sling can be adjusted on the basis of thickness of the liver. The sling applies gentle, atraumatic "pulling" traction and is especially useful for exposure of the right posterior sector. We also use external band retraction to align the transection plane with the camera.5 Both also provide countertraction when advancing instruments into a firm or fibrotic liver. These techniques are commonly used in our MIS practice, and we have found them to be cost-efficient, easily reproducible, and effective.

Development of a Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration of Imaging Features.

BACKGROUND: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. METHODS: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. RESULTS: We identified 383 patients with HCC with imaging and survival outcomes, n = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. CONCLUSIONS: Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC.

Utilizing risk-stratified pathways to personalize post-hepatectomy discharge planning: A contemporary analysis of 1,354 patients.

BACKGROUND: While risk-stratified post-hepatectomy pathways (RSPHPs) reduce length-of-stay, can they stratify hepatectomy patients by risk of early postoperative events. METHODS: 90-day outcomes from consecutive hepatectomies were analyzed (1/1/2017-12/31/2021). Pre/post-pathway analysis was performed for pathways: minimally invasive surgery ("MIS"); non-anatomic resection/left hepatectomy ("low-intermediate risk"); right/extended hepatectomy ("high-risk"); "Combination" operations. Time-to-event (TTE) analyses for readmission and interventional radiology procedures (IRPs) was performed. RESULTS: 1354 patients were included: MIS/n= â€‹119 (9 â€‹%); low-intermediate risk/n= â€‹443 (33 â€‹%); high-risk/n= â€‹328 (24 â€‹%); Combination/n= â€‹464 (34 â€‹%). There was no difference in readmission (pre: 13 â€‹% vs. post:11.5 â€‹%, p â€‹= â€‹0.398). There were fewer readmissions in post-pathway patients amongst MIS, low-intermediate risk, and Combination patients (all p â€‹> â€‹0.1). 114 (8.4 â€‹%) patients required IRPs. Time-to-readmission and time-to-IR-procedure plots demonstrated lower plateaus and flatter slopes for MIS/low-intermediate-risk pathways post-pathway implementation (p â€‹< â€‹0.001). CONCLUSION: RSPHPs can reliably stratify patients by risks of readmission or need for an IR procedure by predicting the most frequent period for these events.

Local Therapy Improves Survival for Early Recurrence After Resection of Colorectal Liver Metastases.

BACKGROUND: Early recurrence following hepatectomy for colorectal liver metastases (CLM) is associated with worse survival; yet, impact of further local therapy is unclear. We sought to evaluate whether local therapy benefits patients with early recurrence following hepatectomy for CLM. METHODS: Clinicopathologic and survival outcomes of patients managed with hepatectomy for CLM (1/2001-12/2020) were queried from a prospectively maintained database. Timing of recurrence was stratified as early (recurrence-free survival [RFS] < 6 months), intermediate (RFS 6-12 months), and later (RFS > 12 months). Local therapy was defined as ablation, resection, or radiation. RESULTS: Of 671 patients, 541 (81%) recurred with 189 (28%) early, 180 (27%) intermediate, and 172 (26%) later recurrences. Local therapy for recurrence resulted in improved survival, regardless of recurrence timing (early 78 vs. 32 months, intermediate 72 vs. 39 months, later 132 vs. 65 months, all p < 0.001). Following recurrence, treatment with local therapy (hazard ratio [HR] = 0.24), liver and extrahepatic recurrence (HR = 1.81), RAS + TP53 co-mutation (HR = 1.52), and SMAD4 mutation (HR = 1.92) were independently associated with overall survival (all p ≤ 0.002). Among patients with recurrence treated by local therapy, patients older than 65 years (HR 1.79), liver and extrahepatic recurrence (HR 2.05), primary site or other recurrence (HR 1.90), RAS-TP53 co-mutation (HR 1.63), and SMAD4 mutation (HR 2.06) had shorter post-local therapy survival (all p ≤ 0.04). CONCLUSIONS: While most patients recur after hepatectomy for CLM, local therapy may result in long-term survival despite early recurrence. Somatic mutational profiling may help to guide the multidisciplinary consideration of local therapy after recurrence.

Laparoscopic transverse abdominis plane block: how I do it and a cost efficiency analysis.

PURPOSE: To determine the efficacy and efficiency of laparoscopic transverse abdominis plane block (Lap-TAP) in patients undergoing pancreatoduodenectomy and gastrectomy compared to those of ultrasound-guided TAP (US-TAP). METHODS: We retrospectively analyzed the records of patients who underwent open or minimally invasive (MIS) pancreatoduodenectomy and major gastrectomy with the use of Lap-TAP or US-TAP at our institution between November 1, 2018, and September 30, 2021. We compared the estimated time and cost associated with Lap-TAP and US-TAP. We also compared postoperative opioid use and pain scores between patients who underwent open laparotomy with these TAPs. RESULTS: A total of 194 patients were included. Overall, 114 patients (59%) underwent pancreatectomy, and 80 patients (41%) underwent gastrectomy. Additionally, 138 patients (71%) underwent an open procedure, and 56 patients (29%) underwent MIS. A total of 102 patients (53%) underwent US-TAP, and 92 (47%) underwent Lap-TAP. The median time to skin incision was significantly shorter in the Lap-TAP group (US-TAP, 59 min vs. Lap-TAP, 45 min; P < 0.001), resulting in an estimated reduction in operation cost by $602. Pain scores and postoperative opioid use were similar between Lap-TAP and US-TAP among open surgery patients, indicating equivalent pain control between Lap-TAP and US-TAP. CONCLUSION: Lap-TAP was equally effective in pain control as US-TAP after pancreatectomy and gastrectomy, and Lap-TAP can reduce operation time and cost. Lap-TAP is considered the preferred approach for MIS pancreatectomy and gastrectomy, which occasionally needs conversion to laparotomy.

The Gut Microbiome as a Biomarker and Therapeutic Target in Hepatocellular Carcinoma.

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome's role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy.

Treatment Disparities Partially Mediate Socioeconomic- and Race/Ethnicity-Based Survival Disparities in Stage I-II Hepatocellular Carcinoma.

BACKGROUND: Low socioeconomic status (SES) patients with early-stage hepatocellular carcinoma (HCC) receive procedural treatments less often and have shorter survival. Little is known about the extent to which these survival disparities result from treatment-related disparities versus other causal pathways. We aimed to estimate the proportion of SES-based survival disparities that are mediated by treatment- and facility-related factors among patients with stage I-II HCC. METHODS: We analyzed patients aged 18-75 years diagnosed with stage I-II HCC in 2008-2016 using the National Cancer Database. Inverse odds weighting mediation analysis was used to calculate the proportion mediated by three mediators: procedure type, facility volume, and facility procedural interventions offered. Intersectional analyses were performed to determine whether treatment disparities played a larger role in survival disparities among Black and Hispanic patients. RESULTS: Among 46,003 patients, 15.0% had low SES, 71.6% had middle SES, and 13.4% had high SES. Five-year overall survival was 46.9%, 39.9%, and 35.7% among high, middle, and low SES patients, respectively. Procedure type mediated 45.9% (95% confidence interval [CI] 31.1-60.7%) and 36.7% (95% CI 25.7-47.7%) of overall survival disparities for low and middle SES patients, respectively, which was more than was mediated by the two facility-level mediators. Procedure type mediated a larger proportion of survival disparities among low-middle SES Black (46.6-48.2%) and Hispanic patients (92.9-93.7%) than in White patients (29.5-29.7%). CONCLUSIONS: SES-based disparities in use of procedural interventions mediate a large proportion of survival disparities, particularly among Black and Hispanic patients. Initiatives aimed at attenuating these treatment disparities should be pursued.

Incidence of and Risk Factors for Incisional Hernia After Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: Incisional hernia (IH) is common after major abdominal surgery; however, the incidence after hepatectomy for cancer has not been described. We analyzed incidence of and risk factors for IH after hepatectomy for colorectal liver metastases (CLM). METHODS: Patients who underwent open hepatectomy with midline or reverse-L incision for CLM at a single institution between 2010 and 2018 were retrospectively analyzed. Postoperative CT scans were reviewed to identify IH and the time from hepatectomy to hernia. Cumulative IH incidence was calculated using competing risk analysis. Risk factors were assessed using Cox proportional hazards model analysis. The relationship between IH incidence and preoperative body mass index (BMI) was estimated using a generalized additive model. RESULTS: Among 470 patients (median follow-up: 16.9 months), IH rates at 12, 24, and 60 months were 41.5%, 51.0%, and 59.2%, respectively. Factors independently associated with IH were surgical site infection (HR: 1.54, 95% CI 1.16-2.06, P = 0.003) and BMI > 25 kg/m2 (HR: 1.94, 95% CI 1.45-2.61, P < 0.001). IH incidence was similar in patients undergoing midline and reverse-L incisions and patients who received and did not receive a bevacizumab-containing regimen. The 1-year IH rate increased with increasing number of risk factors (zero: 22.2%; one: 46.8%; two: 60.3%; P < 0.001). Estimated IH incidence was 10% for BMI of 15 kg/m2 and 80% for BMI of 40 kg/m2. CONCLUSION: IH is common after open hepatectomy for CLM, particularly in obese patients and patients with surgical site infection. Surgeons should consider risk-mitigation strategies, including alternative fascial closure techniques.

Definitive Liver Radiotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Metastases.

Introduction: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT. Methods: We reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose was 97.5 Gy (interquartile range 80.5-97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazard modeling. Results: We identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow-up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8-11) and 21 months (CI: 17-26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; p = 0.001). On multivariable propensity score-matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; p = 0.005) and receipt of L-RT (HR: 0.40; p = 0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; p < 0.001). Conclusion: For M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS versus those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted.