Safety and effectiveness of portal vein embolization after hepatic arterial infusion therapy.

Portal vein embolization (PVE) is a potential tool useful for inducing future liver remnant (FLR) hypertrophy in patients with advanced hepatic malignancies who are at high risk of hepatic insufficiency if treated by surgical resection. However, the safety and effectiveness of PVE in the context of patients who have undergone hepatic arterial infusion (HAI) is unknown. This retrospective, single-center study identified nine patients who underwent PVE after HAI between January 2015 and December 2022. There were no major adverse events, including biliary, or high-grade liver failure. Analysis showed an increase in standardized FLR from 21.1 ± 2.4% to 34.8 ± 2.1% over 9.8 ± 1.2 weeks, with a mean kinetic growth rate of 2.2 ± 0.6%. The study suggested compatibility of PVE after HAI. Patients who have undergone HAI therapy should not be excluded from consideration of PVE as part of their operative clearance strategy.

Clinician overconfidence in visual estimation of the posthepatectomy liver remnant volume: A proximal source of liver failure after major hepatic resection?

BACKGROUND: Post-hepatectomy liver failure is a source of morbidity and mortality after major hepatectomy and is related to the volume of the future liver remnant. The accuracy of a clinician's ability to visually estimate the future liver remnant without formal computed tomography liver volumetry is unknown. METHODS: Twenty physicians in diagnostic radiology, interventional radiology, and hepatopancreatobiliary surgery reviewed 20 computed tomography scans of patients without underlying liver pathology who were not scheduled for liver resection. We evaluated clinician accuracy to estimate the future liver remnant for 3 hypothetical major hepatic resections: left hepatectomy, right hepatectomy, and right trisectionectomy. The percent-difference between the mean and actual computed tomography liver volumetry (mean percent difference) was tested along with specialty differences using mixed-effects regression analysis. RESULTS: The actual future liver remnant (computed tomography liver volumetry) remaining after a hypothetical left hepatectomy ranged from 59% to 75% (physician estimated range: 50%-85%), 23% to 40% right hepatectomy (15%-50%), and 13% to 29% right trisectionectomy (8%-39%). For right hepatectomy, the mean future liver remnant was overestimated by 95% of clinicians with a mean percent difference of 22% (6%-45%; P < .001). For right trisectionectomy, 90% overestimated the future liver remnant by a mean percent difference of 25% (6%-50%; P < .001). Hepatopancreatobiliary surgeons overestimated the future liver remnant for proposed right hepatectomy and right trisectionectomy by a mean percent difference of 25% and 34%, respectively. Based on years of experience, providers with <10 years of experience had a greater mean percent difference than providers with 10+ years of experience for hypothetical major hepatic resections, but was only significantly higher for left hepatectomy (9% vs 6%, P = .002). CONCLUSION: A clinician's ability to visually estimate the future liver remnant volume is inaccurate when compared to computed tomography liver volumetry. Clinicians tend to overestimate the future liver remnant volume, especially in patients with a small future liver remnant where the risk of posthepatectomy liver failure is greatest.

Referral and treatment patterns in pancreatic acinar cell carcinoma: A regional population-level analysis.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas. We evaluated the effect disease stage, surgical intervention, and institutional volume status plays in survival. METHODS: We queried the Oregon State Cancer Registry for patients with PACC from 1997 to 2018. Treatment and referral patterns were analyzed, and overall survival (OS) was evaluated with Kaplan-Meier and Cox-proportional hazard analysis. RESULTS: 43 patients were identified. Median OS was 33.1 and 7.1 months in those with locoregional and metastatic disease respectively (p â€‹= â€‹0.008). Surgical intervention was associated with improved OS (hazard ratio 0.28, p â€‹< â€‹0.0001). High volume center (HVC) care trended towards improving OS. While the majority of cases were diagnosed at low volume centers (74%), referral to HVCs was rare (n â€‹= â€‹4) and limited to advanced (stage III/IV) disease. CONCLUSION: Stage and surgical resection influence survival outcomes in PACC, more data is needed to delineate the impact of institutional volume status.

Metastasectomy for metastatic melanoma in the era of effective systemic therapy.

INTRODUCTION: Effective systemic therapy (EST) in patients with metachronous metastatic melanoma (MMM) improves survival and alters surgical decision-making. Surgical metastasectomy is another treatment option, however, it is unclear if metastasectomy confers survival benefit. This study seeks to identify any survival benefit associated with surgical management of MMM. METHODS: Patients with MMM from 2009 to 2021 were grouped by receipt of metastasectomy and treatment era (pre-versus post-EST). Overall survival (OS) was calculated from date of metastasis and evaluated with Kaplan-Meier analysis. RESULTS: Our dataset identified 226 patients with MMM; 32% were diagnosed pre-EST. On Kaplan-Meier analysis, OS was improved for patients undergoing treatment post-versus pre-EST (p < 0.001). In the post-EST era, metastasectomy was associated with an increase in OS compared to no resection (p = 0.022). CONCLUSIONS: In the post-EST group, EST paired with metastasectomy was associated with improved OS compared to the pre-EST group, suggesting persistent evidence of a survival benefit from metastasectomy.

Updated Management of Colorectal Cancer Liver Metastases: Scientific Advances Driving Modern Therapeutic Innovations.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States and accounts for an estimated 1 million deaths annually worldwide. The liver is the most common site of metastatic spread from colorectal cancer, significantly driving both morbidity and mortality. Although remarkable advances have been made in recent years in the management for patients with colorectal cancer liver metastases, significant challenges remain in early detection, prevention of progression and recurrence, and in the development of more effective therapeutics. In 2017, our group held a multidisciplinary state-of-the-science symposium to discuss the rapidly evolving clinical and scientific advances in the field of colorectal liver metastases, including novel early detection and prognostic liquid biomarkers, identification of high-risk cohorts, advances in tumor-immune therapy, and different regional and systemic therapeutic strategies. Since that time, there have been scientific discoveries translating into therapeutic innovations addressing the current management challenges. These innovations are currently reshaping the treatment paradigms and spurring further scientific discovery. Herein, we present an updated discussion of both the scientific and clinical advances and future directions in the management of colorectal liver metastases, including adoptive T-cell therapies, novel blood-based biomarkers, and the role of the tumor microbiome. In addition, we provide a comprehensive overview detailing the role of modern multidisciplinary clinical approaches used in the management of patients with colorectal liver metastases, including considerations toward specific molecular tumor profiles identified on next generation sequencing, as well as quality of life implications for these innovative treatments.

The genomics of liver metastases from colon and rectal cancer: An Invited Commentary (invitation from Lee Ocuin, MD and Kevin Behrns, MD) for the special issue of "Management of Advanced Primary and Secondary Liver Malignancies".

Over the past two decades, the treatment of patients with cancer has become increasingly structured around the identification of cancer mutations genetically driving the disease. Upfront knowledge of these data has implications for both the selection and omission of certain cytotoxic and targeted therapies. For patients with colon or rectal cancer metastatic to the liver, next-generation sequencing to identify these key mutational drivers should be done at the outset of diagnosis to understand the full spectrum of treatment options available to a patient. Mutational profiling for patients with colorectal liver metastasis initially led to the recognition of treatment resistance to epidermal growth factor inhibitors in patients with a KRAS mutation and now has expanded to include other targeted options. As the treatment options for patients with colorectal liver metastasis continue to evolve, it is increasingly important to integrate genomic data into selecting patients who will benefit from hepatic resection, ablative techniques, and liver-directed therapy. Herein, we review the most common mutations encountered in treating patients with colorectal liver metastasis, focusing specifically on epidermal growth factor receptor, KRAS/NRAS, BRAF, and the mismatch repair pathway with resultant implications to the medical and surgical treatment for these patients.

Neoadjuvant therapy does not impact the biliary microbiome in patients with pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) often impinges on the biliary tree and obstruction necessitates stent placement increasing the risk of surgical site infections (SSIs). We sought to explore the impact of neoadjuvant therapy on the biliary microbiome and SSI risk in patients undergoing resection. METHODS: A retrospective analysis was performed on 346 patients with PDAC who underwent resection at our institution from 2008 to 2021. Univariate and multivariate methods were utilized for analysis. RESULTS: Biliary stenting rates were similar between groups but resulted in increased bile culture positivity (97% vs. 15%, p < 0.001). Culture positivity did not differ between upfront resection or neoadjuvant chemotherapy (NAC) (77% vs. 80%, p = 0.60). NAC-alone versus neoadjuvant chemoradiotherapy did not impact biliary positivity (80% vs. 79%, p = 0.91), nor did 5-fluorouracil versus gemcitabine-based regimens (73% vs. 85%, p = 0.19). While biliary stenting increased incisional SSI risk (odds ratios [OR]: 3.87, p = 0.001), NAC did not (OR: 0.83, p = 0.54). Upfront resection, NAC, and chemoradiotherapy were not associated with biliary organism-specific changes or antibiotic resistance patterns. CONCLUSIONS: Biliary stenting is the greatest predictor for positive biliary cultures and SSIs in resected PDAC patients. Neither NAC nor radiotherapy impact bile culture positivity, speciation, rates, or antibiotic resistance patterns, and perioperative antibiotic prophylaxis should not differ.

High-volume centers are associated with higher receipt of combined therapy in stage III pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at a locally advanced stage with vascular involvement which was previously viewed as a contraindication to resection. However, high-volume centers are increasingly capable of resecting complex tumors. We aimed to explore patterns of treatment that are uncharacterized on a population level. METHODS: A statewide registry was queried from 2003 to 2018 for stage III PDAC. Stepwise logistic regression and Kaplan-Meier were used for statistical analysis. RESULTS: We identified 424 eligible patients. 348 (82%) received chemotherapy, 17 (4.0%) received resection, and 59 (13.9%) received both; median survival was 10.7, 8.7, and 22.7 months, respectively (P < 0.001). High-volume centers (≥20 cases per year; OR 5.40 [95% CI: 2.76, 10.58], P < 0.001) and later year of diagnosis (OR 1.12/year [95% CI: 1.04, 1.20], P = 0.004) were associated with higher odds of receiving combined therapy. CONCLUSION: PDAC patients with vascular involvement who receive both systemic chemotherapy and surgical resection have improved overall survival. High-volume centers are independently associated with higher odds of receiving combined systemic therapy and surgical resection.

Care at high-volume centers is associated with improved outcomes for patients with pancreatic neuroendocrine tumors: A population-level analysis.

BACKGROUND AND OBJECTIVES: Primary resection and debulking of liver metastases have been associated with improved survival in pancreatic neuroendocrine tumors (PNETs). The treatment patterns and outcomes differences between low-volume (LV) institutions and high-volume (HV) institutions remains unstudied. METHODS: A statewide cancer registry was queried for patients with nonfunctional PNET from 1997 to 2018. LV institutions were defined as treating <5 newly diagnosed patients with PNET per year, while HV institutions treated ≥5. RESULTS: We identified 647 patients: 393 with locoregional (n = 236 HV care, n = 157 LV care) and 254 with metastatic disease (n = 116 HV care, n = 138 LV care). Patients with HV care had improved disease-specific survival (DSS) compared to patients with LV care for both locoregional (median 63 vs. 32 months, p < 0.001) and metastatic disease (median 25 vs. 12 months, p < 0.001). In patients with metastatic disease, primary resection (hazard ratio [HR]: 0.55, p = 0.003) and HV institution (HR: 0.63, p = 0.002) were independently associated with improved DSS. Furthermore, diagnosis at a HV center was independently associated with higher odds of receiving primary site surgery (odds ratio [OR]: 2.59, p = 0.01) and metastasectomy (OR: 2.51, p = 0.03). CONCLUSIONS: Care at HV centers is associated with improved DSS in PNET. We recommend referral of all patients with PNETs to HV centers.

The need for integrated clinical and administrative data models for risk adjustment in assessment of the cost transplant care.

INTRODUCTION: Value-based purchasing requires accurate techniques to appropriately measure both outcomes and cost with robust adjustment for differences in severity of illness. Traditional methods to adjust cost estimates have exclusively used administrative data derived from billing claims to identify comorbidity and complications. Transplantation uniquely has accurate national clinical registry data that can be used to supplement administrative data. METHODS: Administrative claims from the Vizient, Inc, Clinical Data Base (CDB) were linked with clinical records from the Scientific Registry for Transplant Recipients for 76 liver and 109 kidney transplant programs. Using either or both datasets, we fitted a regression model to the total direct cost of care for 16,649 kidney and 6058 liver transplants. RESULTS: The proportion of variation explained by these risk-adjustment models increased significantly when combined administrative and clinical data were used for kidney (administrative only R2 = .069, clinical only R2 = .047, combined R2 = .14, p < .0001) and liver (administrative only R2 = .28, clinical only R2 = .25, combined R2 = .33, p < .0001). CONCLUSION: Incorporating accurate clinical data into risk-adjustment methodologies can improve risk adjustment methodologies; however, as majority of variation in cost remains unexplained by these risk-adjustment models further work is needed to accuracy assess transplant value.

Technology-Enabled Care and Artificial Intelligence in Kidney Transplantation.

Purpose of Review: Artificial intelligence (AI), machine learning, and technology-enabled remote patient care have evolved rapidly and have now been incorporated into many aspects of medical care. Transplantation is fortunate to have large data sets upon which machine learning algorithms can be constructed. AI are now available to improve pretransplant management, donor selection, and post-operative management of transplant patients. Recent Findings: Changes in patient and donor characteristics warrant new approaches to listing and organ acceptance practices. Machine learning has been employed to optimize donor selection to identify patients likely to benefit from transplantation of higher risk organs, increasing organ discard and reducing waitlist mortality. These models have greater precisions and predictive ability than currently employed metrics including the Kidney Donor Profile Index and the expected posttransplant survival models. After transplant, AI tools have been developed to optimize immunosuppression management, track patients adherence, and assess graft survival. Summary: AI and technology-enabled management tools are now available throughout the transplant journey. Unfortunately, those are frequently not available at the point of decision (patient listing, organ acceptance, posttransplant clinic), limiting utilization. Incorporation of these tools into the EMR, the Donor Net® organ offer system, and mobile devices is vital to ensure widespread adoption.

A simple risk-based reimbursement system for kidney transplant.

Transplant centers were challenged by the Executive Order on Advancing Kidney health to increase access to kidney transplant (KTx) by accepting higher risk patients and organs. However, Medicare reimbursement for KTx does not include adjustment for major complicating comorbidities (MCCs) like other transplants. The prevalence of MCCs was assessed for KTx performed from 10/15 to 10/19 at a single academic center, using Medicare ICD10 MCC criteria exclusive of end-stage kidney disease. KTx hospital resource utilization and estimated margin, assuming Medicare reimbursement, were determined for cases with and without MCC. Among 260 KTx recipients, 49 (19%) had an MCC. Patients with MCCs had longer wait times (1121 days vs 703 days, P < .001); however, there were no differences in age, gender, race, or diagnosis. Donor characteristics associated with an MCC included greater cold ischemic time (1042 vs 670 minutes, P < .001) and fewer living donor KTx (9% vs 32%, P < .001). KTx cost, exclusive of organ acquisition, was 31% higher (MCC: $38 293 vs No MCC: $29 132) and estimated margin was markedly lower (-$7750 vs -$1001, P = .001). In conclusion, KTx with qualifying MCCs resulted in significant financial losses and modification of KTx payment methodology to align with other organ transplants is needed.