Safety and efficacy of percutaneous image-guided ablation for soft tissue sarcoma metastases to the liver.

PURPOSE: To evaluate outcomes following percutaneous image-guided ablation of soft tissue sarcoma metastases to the liver. MATERIALS AND METHODS: A single-institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image-guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow-up after ablation were excluded. The primary outcome was local tumor progression-free survival (LPFS). Secondary outcomes included overall survival, liver-specific progression-free survival. and chemotherapy-free survival. RESULTS: Fifty-five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes were leiomyosarcoma (23/55), followed by gastrointestinal stromal tumor (22/55). The median treated liver lesions was 2 (range, 1-8), whereas the median size of metastases were 1.8 cm (0.3-8.7 cm). Complete response at 2 months was achieved in 90.5% of the treated lesions. LPFS was 83% at 1 year and 80% at 2 years. Liver-specific progression-free survival was 66% at 1 year and 40% at 2 years. The overall survival at 1 and 2 years was 98% and 94%. The chemotherapy-free holiday from the start of ablation was 71.2% at 12 months. The complication rate was 3.6% (2/55); one of the complications was Common Terminology Criteria for Adverse Events grade 3 or higher. LPFS subgroup analysis for leiomyosarcoma versus gastrointestinal stromal tumor suggests histology-agnostic outcomes (2 years, 89% vs 82%, p = .35). CONCLUSION: Percutaneous image-guided liver ablation of soft tissue sarcoma metastases is safe and efficacious.

Image-Guided Deployment and Monitoring of a Novel Tungsten Nanoparticle-Infused Radiopaque Absorbable Inferior Vena Cava Filter in a Swine Model.

PURPOSE: To improve radiopacity of radiolucent absorbable poly-p-dioxanone (PPDO) inferior vena cava filters (IVCFs) and demostrate their effectiveness in clot-trapping ability. MATERIALS AND METHODS: Tungsten nanoparticles (WNPs) were incorporated along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of WNPs. The physicochemical and in vitro and in vivo imaging properties of PPDO IVCFs with WNPs with single-polymer PHB (W-P) were compared with those of WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). RESULTS: In vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physicomechanical properties of the PPDO sutures. W-P- and W-PB-coated IVCFs were deployed successfully into the inferior vena cava of pig models with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring of in vivo IVCFs over a 12-week period showed a drastic decrease in radiopacity at Week 3 for both filters. CONCLUSIONS: The results highlight the utility of nanoparticles (NPs) and polymers for enhancing radiopacity of medical devices. Different methods of incorporating NPs and polymers can still be explored to improve the effectiveness, safety, and quality of absorbable IVCFs.

Gold Nanoparticles for Monitoring of Mesenchymal Stem-Cell-Loaded Bioresorbable Polymeric Wraps for Arteriovenous Fistula Maturation.

Mesenchymal stem cell (MSC)-seeded polymeric perivascular wraps have been shown to enhance arteriovenous fistula (AVF) maturation. However, the wraps' radiolucency makes their placement and integrity difficult to monitor. Through electrospinning, we infused gold nanoparticles (AuNPs) into polycaprolactone (PCL) wraps to improve their radiopacity and tested whether infusion affects the previously reported beneficial effects of the wraps on the AVF's outflow vein. Sprague Dawley rat MSCs were seeded on the surface of the wraps. We then compared the effects of five AVF treatments-no perivascular wrap (i.e., control), PCL wrap, PCL + MSC wrap, PCL-Au wrap, and PCL-Au + MSC wrap-on AVF maturation in a Sprague Dawley rat model of chronic kidney disease (n = 3 per group). Via micro-CT, AuNP-infused wraps demonstrated a significantly higher radiopacity compared to that of the wraps without AuNPs. Wraps with and without AuNPs equally reduced vascular stenoses, as seen via ultrasonography and histomorphometry. In the immunofluorescence analysis, representative MSC-seeded wraps demonstrated reduced neointimal staining for markers of infiltration with smooth muscle cells (α-SMA), inflammatory cells (CD45), and fibroblasts (vimentin) compared to that of the control and wraps without MSCs. In conclusion, AuNP infusion allows in vivo monitoring via micro-CT of MSC-seeded polymeric wraps over time, without compromising the benefits of the wrap for AVF maturation.

Comprehensive Complication Index Validates Improved Outcomes Over Time Despite Increased Complexity in 3707 Consecutive Hepatectomies.

OBJECTIVE: The aim of this study was to evaluate trends over time in perioperative outcomes for patients undergoing hepatectomy. BACKGROUND: As perioperative care and surgical technique for hepatectomy have improved, the indications for and complexity of liver resections have evolved. However, the resulting effect on the short-term outcomes over time has not been well described. METHODS: Consecutive patients undergoing hepatectomy during 1998 to 2015 at 1 institution were analyzed. Perioperative outcomes, including the comprehensive complication index (CCI), were compared between patients who underwent hepatectomy in the eras 1998 to 2003, 2004 to 2009, and 2010 to 2015. RESULTS: The study included 3707 hepatic resections. The number of hepatectomies increased in each era (794 in 1998 to 2003, 1402 in 2004 to 2009, and 1511 in 2010 to 2015). Technical complexity increased over time as evidenced by increases in the rates of major hepatectomy (20%, 23%, 30%, P < 0.0001), 2-stage hepatectomy (0%, 3%, 4%, P < 0.001), need for portal vein embolization (5%, 9%, 9%, P = 0.001), preoperative chemotherapy for colorectal liver metastases (70%, 82%, 89%, P < 0.001) and median operative time (180, 175, 225 minutes, P < 0.001). Significant decreases over time were observed in median blood loss (300, 250, 200 mL, P < 0.001), transfusion rate (19%, 15%, 5%, P < 0.001), median length of hospitalization (7, 7, 6 days, P < 0.001), rates of CCI ≥26.2 (20%, 22%, 16%, P < 0.001) and 90-day mortality (3.1%, 2.6%, 1.3%, P < 0.01). On multivariable analysis, hepatectomy in the most recent era 2010 to 2015 was associated with a lower incidence of CCI ≥26.2 (odds ratio 0.7, 95% confidence interval 0.6-0.8, P < 0.0001). CONCLUSION: Despite increases in complexity over an 18-year period, continued improvements in surgical technique and perioperative outcomes yielded a resultant decrease in CCI in the most current era.

Hepatic vein embolization after portal vein embolization to induce additional liver hypertrophy in patients with metastatic colorectal carcinoma.

OBJECTIVES: To assess the effect of salvage hepatic vein embolization (HVE) on the volume of the future liver remnant (FLR) for patients with metastatic colorectal cancer (mCRC) and inadequate hypertrophy following initial portal vein embolization (PVE). METHODS: From April 2011 to October 2018, 9 patients with mCRC underwent HVE following PVE. The right or middle hepatic vein was embolized with coils and/or vascular plugs. Liver volumes were calculated at baseline, following PVE, and following HVE, in order to assess the hypertrophic effect of PVE and HVE on the FLR. RESULTS: Nine patients underwent HVE (n = 3, right HVE; n = 6, middle HVE) because of inadequate FLR hypertrophy following PVE. The standardized FLR increased from 0.16 (median, range 0.08-0.24) at baseline to 0.22 (median, range 0.13-0.29) following PVE (p = 0.0005) to 0.26 (median, range 0.19-0.37) following HVE (p = 0.0050). HVE was performed 40 days (median, range 19-128 days) following PVE, and assessment of FLR hypertrophy was performed 41 days (median, range 19-92 days) following HVE. Four of nine patients underwent hepatectomy; 5 patients failed to undergo hepatectomy (n = 3, inadequate hypertrophy; n = 1, disease progression; n = 1, portal hypertension). One patient required repeat HVE due to a patent accessory vein. CONCLUSIONS: Salvage HVE is an effective technique to induce additional FLR hypertrophy in patients with mCRC and inadequate FLR after initial PVE. KEY POINTS: • Hepatic vein embolization is effective to induce additional liver hypertrophy in surgical patients with metastatic colorectal carcinoma and inadequate hypertrophy after portal vein embolization. • Increases in future liver remnant volume are feasible in patients who receive hepatotoxic neoadjuvant systemic therapy for metastatic colorectal carcinoma. • Sequential portal vein embolization and hepatic vein embolization can be a viable technique to induce liver hypertrophy in patients with small baseline future liver remnant volumes (< 20%).

Transjugular Intrahepatic Portosystemic Shunts Reduce Variceal Bleeding and Improve Survival in Patients with Cirrhosis: A Population-Based Analysis.

PURPOSE: To investigate from a population health perspective the effects of transjugular intrahepatic portosystemic shunt (TIPS) creation on recurrent variceal bleeding and survival in patients with cirrhosis. MATERIALS AND METHODS: Patients with cirrhosis who presented to outpatient and acute-care hospitals in California (2005-2011) and Florida (2005-2014) with variceal bleeding comprised the study cohort. Patients entered the study cohort at their first presentation for variceal bleeding; all subsequent hospital encounters were then evaluated to determine subsequent interventions, complications, and mortality data. RESULTS: A total of 655,577 patients with cirrhosis were identified, of whom 42,708 (6.5%) had at least 1 episode of variceal bleeding and comprised the study cohort. The median follow-up time was 2.61 years. A TIPS was created in 4,201 (9.8%) of these patients. There were significantly greater incidences of coagulopathy (83.9% vs 72.8%; P < .001), diabetes (45.5% vs 38.8%; P < .001), and hepatorenal syndrome (15.3% vs 12.5%; P < .001) in TIPS recipients vs those without a TIPS. Following propensity-score matching, TIPS recipients were found to have improved overall survival (82% vs 77% at 12 mo; P < .001) and a lower rate of recurrent variceal bleeding (88% vs 83% recurrent bleeding-free survival at 12 months,; P < .001) than patients without a TIPS. Patients with a TIPS had a significant increase in encounters for hepatic encephalopathy vs those without (1.01 vs 0.49 per year; P < .001). CONCLUSIONS: TIPS improves recurrent variceal bleeding rates and survival in patients with cirrhosis complicated by variceal bleeding. However, TIPS creation is also associated with a significant increase in hepatic encephalopathy.

Portomesenteric Venous Stenting for Palliation of Ascites and Variceal Bleeding Caused by Prehepatic Portal Hypertension.

BACKGROUND: The purpose of this study was to evaluate percutaneous transhepatic portal vein stenting (PVS) for palliation of refractory ascites and/or variceal bleeding caused by extrahepatic portomesenteric venous stenosis in patients with pancreaticobiliary cancer. MATERIALS AND METHODS: A single-institution, retrospective review of patients who underwent PVS between January 2007 and July 2015 was performed. A total of 38 patients were identified, of whom 28 met the inclusion criterion of PVS performed primarily for refractory ascites or variceal bleeding. In addition to technical success and overall survival, clinical success was measured by fraction of remaining life palliated. The palliative effect of PVS was also quantified by measuring changes in liver and ascites volumes after the procedure. RESULTS: Technical success was 93% (26/28). Stent deployment involved more than one portomesenteric vessel in most patients (20/26). The cumulative probability of symptom recurrence at 6, 12, 18, and 24 months was 12%, 16%, 26%, and 40%, respectively. There was a significant difference (p < .001) in the probability of symptom recurrence, recurrence of abdominal ascites, and increase in liver volume between patients whose stents remained patent and those whose stents demonstrated partial or complete occlusion. The mean fraction of remaining life palliated was 87%. All but two patients were found to have improvement in clinical symptoms for the majority of their lives after the procedure. There were no major or minor complications. CONCLUSION: As a low-risk procedure with a high clinical success rate, PVS can play a substantial role in improving quality of life in patients with portomesenteric stenoses. IMPLICATIONS FOR PRACTICE: Portomesenteric venous stenosis is a challenging complication of pancreaticobiliary malignancy. Portomesenteric stenoses can lead to esophageal, gastric, and mesenteric variceal bleeding, as well as abdominal ascites. The purpose of this study was to evaluate the safety and efficacy of portal vein stenting (PVS) in patients with cancer who have symptomatic portal hypertension caused by portomesenteric venous compression. As a low-risk procedure with a high clinical success rate, PVS can play a substantial role in improving quality of life in patients with portomesenteric stenoses.

Impact of Prior Hepatectomy History on Local Tumor Progression after Percutaneous Ablation of Colorectal Liver Metastases.

PURPOSE: To test the hypothesis that, given the current resection eligibility criteria for colorectal liver metastasis (CLM), prior hepatectomy would be associated with improved local tumor control and survival after percutaneous ablation of CLMs. MATERIALS AND METHODS: This single-institution retrospective study included 82 consecutive patients with 97 CLMs treated with ablation (radiofrequency ablation, microwave ablation, or cryoablation) from January 2005 to December 2014. Local tumor progression-free survival (LTPFS), recurrence-free survival (RFS) at any organ, and overall survival (OS) were calculated using the Kaplan-Meier method from the time of ablation and compared between patients with (n = 49) and without (n = 33) prior hepatectomy. Cox regression models were used to identify LTPFS predictors. RESULTS: Median overall follow-up period was 28 months (range, 4.5-132 months). Three-year actuarial LTPFS (patient level: 73% vs 34%, P < .001) was significantly higher in patients with than without prior hepatectomy, respectively. Similarly, 3-year RFS (23% vs 9.1%, P = .026) and OS (78% vs 48%, P = .003) were improved in patients with prior hepatectomy. At multivariate analysis, predictors of worse LTPFS were: no prior hepatectomy (hazard ratio [HR] 2.35, 95% confidence interval [CI] 1.02-5.45; P = .045), minimal ablation margin < 5 mm (HR 2.4, 95% CI 1.18-4.87; P = .016), and RAS-mutant tumor (HR 2.65, 95% CI 1.18-5.94; P = .019). CONCLUSIONS: Prior hepatectomy for CLMs is associated with improved local tumor control after percutaneous ablation of post-resection-developed CLMs.

Safety and Efficacy of an Absorbable Filter in the Inferior Vena Cava to Prevent Pulmonary Embolism in Swine.

Purpose To evaluate the immediate and long-term safety as well as thrombus-capturing efficacy for 5 weeks after implantation of an absorbable inferior vena cava (IVC) filter in a swine model. Materials and Methods This study was approved by the institutional animal care and use committee. Eleven absorbable IVC filters made from polydioxanone suture were deployed via a catheter in the IVC of 11 swine. Filters remained in situ for 2 weeks (n = 2), 5 weeks (n = 2), 12 weeks (n = 2), 24 weeks (n = 2), and 32 weeks (n = 3). Autologous thrombus was administered from below the filter in seven swine from 0 to 35 days after filter placement. Fluoroscopy and computed tomography follow-up was performed after filter deployment from weeks 1-6 (weekly), weeks 7-20 (biweekly), and weeks 21-32 (monthly). The infrarenal IVC, lungs, heart, liver, kidneys, and spleen were harvested at necropsy. Continuous variables were evaluated with a Student t test. Results There was no evidence of IVC thrombosis, device migration, caval penetration, or pulmonary embolism. Gross pathologic analysis showed gradual device resorption until 32 weeks after deployment. Histologic assessment demonstrated neointimal hyperplasia around the IVC filter within 2 weeks after IVC filter deployment with residual microscopic fragments of polydioxanone suture within the caval wall at 32 weeks. Each iatrogenic-administered thrombus was successfully captured by the filter until resorbed (range, 1-4 weeks). Conclusion An absorbable IVC filter can be safely deployed in swine and resorbs gradually over the 32-week testing period. The device is effective for the prevention of pulmonary embolism for at least 5 weeks after placement in swine. © RSNA, 2017.

Development of a predictive model for 6 month survival in patients with venous thromboembolism and solid malignancy requiring IVC filter placement.

PURPOSE: Our purpose was to develop a predictive model for short-term survival (i.e. <6 months) following inferior vena cava filter placement in patients with venous thromboembolism (VTE) and solid malignancy. METHODS: Clinical and laboratory parameters were retrospectively reviewed for patients with solid malignancy who received a filter between January 2009 and December 2011 at a tertiary care cancer center. Multivariate Cox proportional hazards modeling was used to assess variables associated with 6 month survival following filter placement in patients with VTE and solid malignancy. Significant variables were used to generate a predictive model. RESULTS: 397 patients with solid malignancy received a filter during the study period. Three variables were associated with 6 month survival: (1) serum albumin [hazard ratio (HR) 0.496, P < 0.0001], (2) recent or planned surgery (<30 days) (HR 0.409, P < 0.0001), (3) TNM staging (stage 1 or 2 vs. stage 4, HR 0.177, P = 0.0001; stage 3 vs. stage 4, HR 0.367, P = 0.0002). These variables were used to develop a predictive model to estimate 6 month survival with an area under the receiver operating characteristic curve of 0.815, sensitivity of 0.782, and specificity of 0.715. CONCLUSIONS: Six month survival in patients with VTE and solid malignancy requiring filter placement can be predicted from three patient variables. Our predictive model could be used to help physicians decide whether a permanent or retrievable filter may be more appropriate as well as to assess the risks and benefits for filter retrieval within the context of survival longevity in patients with cancer.

Safety and diagnostic accuracy of percutaneous biopsy in upper tract urothelial carcinoma.

OBJECTIVE: To assess the diagnostic accuracy and safety of percutaneous biopsy for upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: From 2002 to 2013, 26 upper tract lesions in 24 patients (20 men; median [range] age 67.8 [51.7-85.9] years) were percutaneously biopsied. Analysis was separated based on lesion appearance: (i) mass infiltrating renal parenchyma, (ii) filling defect in the collecting system, (iii) urothelial wall thickening. We tracked immediate complications and tract seeding on follow-up imaging. RESULTS: Of the 26 upper tract lesions, 15 (58%) were masses infiltrating the renal parenchyma (mean [range] size 5.4 [1.1-14.0] cm), six (23%) were urothelial wall thickenings (mean [range] size 0.8 [0.4-1.1] cm), and five (19%) were filling defects within the renal pelvis or calyx (mean [range] size 2.7 [1.0-4.6] cm). Definitive diagnosis of UTUC was made by biopsy in 22 of 26 lesions (85%). Biopsy characterised 14 of 15 infiltrative masses and five of five filling defects; biopsy characterised three of six cases of urothelial wall thickening. CT follow-up was available for 19 patients (73%) at a median (range) of 13.6 (1.0-98.9) months. Three patients (11%) developed recurrence in the nephrectomy bed at 5.6, 9.7, and 29.0 months after biopsy; none were attributed to tract seeding after independent review, because recurrence was remote from the biopsy site. CONCLUSION: Percutaneous biopsy is effective for diagnosis of UTUC, providing tissue diagnosis in 85% of cases. While case reports cite a risk of tract seeding, no cases of recurrence were definitely attributable to percutaneous biopsy. Thus, for upper tract urothelial lesions, which are not amenable to endoscopic biopsy, percutaneous biopsy is a safe and effective technique.

JOURNAL CLUB: Standardizing CT-Guided Biopsy Procedures: Patient Dose and Image Noise.

OBJECTIVE: The objective of this study was to standardize our image acquisition protocol for CT-guided biopsy procedures. MATERIALS AND METHODS: The records of consecutive patients who underwent CT-guided biopsy 3 months before (n = 598 biopsies) and 3 months after (n = 540 biopsies) standardization of our image acquisition protocol were retrospectively reviewed. CT technical parameters were individualized on the basis of the sum of the anteroposterior and transverse dimensions of the patient. Information on patient demographic characteristics, biopsy site, complications associated with the procedure, and diagnostic yield was collected. The radiation dose metrics that were evaluated included the volume CT dose index, dose-length product, and size-specific dose estimate. Image noise was quantified using the SD of the CT number measured in subcutaneous fat. Fisher exact test and one-way ANOVA were used to evaluate statistical significance. RESULTS: The mean dose-length product decreased by 72.3% (from 699.7 to 193.9 mGy × cm; p < 0.0001), and statistically significant decreases in dose-length product were observed when data were stratified according to biopsy site (i.e., lung, solid organ, lymph node, or bone; for all sites, p < 0.0001). The mean size-specific dose estimate decreased by 58.9% (from 125 to 51.4 mGy), which was statistically significant (p < 0.001). Image noise increased during the study period, but this increase was not statistically significantly different among the four biopsy sites (p = 0.46). CONCLUSION: Standardization of the image acquisition protocol used in CT-guided biopsy procedures significantly reduced patient radiation dose and decreased variability in image noise.

Evaluation of liver fibrosis and hepatic venous pressure gradient with MR elastography in a novel swine model of cirrhosis.

PURPOSE: To assess the correlation among MR elastography (MRE) measured liver stiffness (LS), liver fibrosis, and hepatic venous pressure gradient (HVPG) in a swine model of cirrhosis. MATERIALS AND METHODS: Three swine served as controls, and liver fibrosis was induced in eight swine by transarterial embolization. LS and HVPG were obtained at baseline and 4 weeks (prenecropsy) following induction of liver fibrosis. RESULTS: Four weeks following the induction of liver cirrhosis, experimental animals developed an increase in HVPG of 8.0±6.4 mmHg compared with 0.3±1.2 mmHg for controls (P=0.08). Over the same timeframe, mean MRE-measured LS increased 0.82±0.39 kPa for experimental swine and 0.1±0.05 kPa for controls (P=0.01). A positive correlation was observed between increases in HVPG and LS (ρ=0.682; P=0.02). Liver fibrosis was measured on explanted livers at 4 weeks and yielded mean fibrosis scores of 2.8 for experimental animals and 0 for controls (P=0.0016). A positive correlation was observed between higher LS and liver fibrosis (ρ=0.884; P=0.0003). CONCLUSION: MRE is a reliable noninvasive technique to measure LS in a swine model of cirrhosis. Significant positive correlations were observed between LS and HVPG as well as LS and fibrosis.

Efficacy and safety of portal vein embolization for two-stage hepatectomy in patients with colorectal liver metastasis.

PURPOSE: To examine the efficacy and safety of portal vein embolization (PVE) when used during two-stage hepatectomy for bilobar colorectal liver metastases (CLM). MATERIALS AND METHODS: PVE was performed as an adjunct to two-stage hepatectomy in 56 patients with CLM. Absolute future liver remnant (FLR) volumes, standardized FLR ratios, degree of hypertrophy (DH), and complications were analyzed. Segment II and III volumes and DH were also measured separately. All volumetric measurements were compared with a cohort of 96 patients (n = 37 right portal vein embolization [RPVE], n = 59 right portal vein embolization extended to segment IV portal veins [RPVE+4]) in whom PVE was performed before single-stage hepatectomy. RESULTS: For patients who completed RPVE during two-stage hepatectomy (n = 17 of 17), mean absolute FLR volume increased from 272.1 cm(3) to 427.0 cm(3) (P < .0001), mean standardized FLR ratio increased from 0.17 to 0.26 (P < .0001), and mean DH was 0.094. For patients who completed RPVE+4 during two-stage hepatectomy (n = 38 of 39), mean FLR volume increased from 288.7 cm(3) to 424.8 cm(3) (P < .0001), mean standardized FLR increased from 0.18 to 0.26 (P < .0001), and mean DH was 0.083. DH of the FLR was not significantly different between two-stage hepatectomy and single-stage hepatectomy. Complications after PVE occurred in five (8.9%) patients undergoing two-stage hepatectomy. CONCLUSIONS: PVE effectively and safely induced a significant DH in the FLR during two-stage hepatectomy in patients with CLM.

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.

Liver volumetry and liver-regenerative interventions: history, rationale, and emerging tools.

BACKGROUND: Postoperative hepatic insufficiency (PHI) is the most feared complication after hepatectomy. Volume of the future liver remnant (FLR) is one objectively measurable indicator to identify patients at risk of PHI. In this review, we summarized the development and rationale for the use of liver volumetry and liver-regenerative interventions and highlighted emerging tools that could yield new advancements in liver volumetry. METHODS: A review of MEDLINE/PubMed, Embase, and Cochrane Library databases was conducted to identify literature related to liver volumetry. The references of relevant articles were reviewed to identify additional publications. RESULTS: Liver volumetry based on radiologic imaging was developed in the 1980s to identify patients at risk of PHI and later used in the 1990s to evaluate grafts for living donor living transplantation. The field evolved in the 2000s by the introduction of standardized FLR based on the hepatic metabolic demands and in the 2010s by the introduction of the degree of hypertrophy and kinetic growth rate as measures of the FLR regenerative and functional capacity. Several liver-regenerative interventions, most notably portal vein embolization, are used to increase resectability and reduce the risk of PHI. In parallel with the increase in automation and machine assistance to physicians, many semi- and fully automated tools are being developed to facilitate liver volumetry. CONCLUSION: Liver volumetry is the most reliable tool to detect patients at risk of PHI. Advances in imaging analysis technologies, newly developed functional measures, and liver-regenerative interventions have been improving our ability to perform safe hepatectomy.

Pre-procedural and intra-procedural computerized tomography: providing a roadmap for successful adrenal venous sampling procedures.

BACKGROUND AND PURPOSE: Adrenal venous sampling (AVS) is used for the diagnosis of primary hyperaldosteronism. Technical difficulties with right adrenal vein (RAV) catheterization can lead to erroneous results. Our purpose was to delineate the location of the RAV on pre-procedural CT imaging in relation to the location identified during AVS and to report on the impact of successful RAV cannulation with and without the use of intra-procedural CT scanning. METHODS: Retrospective case series including patients who underwent AVS from October 2000 to September 2022. Clinical and laboratory values were abstracted from the electronic medical record. Successful cannulation of the RAV was defined as a selectivity index > 3. RESULTS: 110 patients underwent 124 AVS procedures. Pre-AVS CT imaging was available for 118 AVS procedures. The RAV was identified in 61 (51.7%) CT datasets. Biochemical confirmation of successful RAV cannulation occurred in 98 (79.0%) of 124 AVS procedures. There were 52 (85.2%) procedures in which the RAV was identified on pre-AVS CT and there was biochemical confirmation of successful RAV sampling. Among these 52 procedures, the RAV was localized during AVS at the same anatomic level or within 1 vertebral body level cranial to the level identified on pre-AVS CT in 98.1% of cases. The rate of successful RAV cannulation was higher in patients who underwent intra-procedural CT (93.8% versus 63.9%), P < 0.01. CONCLUSIONS: Pre-AVS and intra-procedural CT images provide an invaluable roadmap that resulted in a higher rate of accurate identification of the RAV and successful AVS procedures; in particular, search for the RAV orifice during AVS can be limited to 1 vertebral body cranial to the level identified on pre-AVS CT imaging and successful cannulation can be confidently verified with intra-procedural CT.

Intraprocedural Versus Initial Follow-up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?

OBJECTIVES: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation. MATERIALS AND METHODS: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation CT and ablation zones on intraprocedural postablation and initial follow-up CT. Prognostic value of MAM to predict LTP was tested using area under the curve and competing-risk regression model. RESULTS: A total of 68 patients (mean age ± standard deviation, 57 ± 12 years; 43 men) with 133 CLMs were included. During a median follow-up of 30.3 months, LTP rate was 17% (22/133). The median volume of ablation zone was 27 mL and 16 mL segmented on intraprocedural and initial follow-up CT, respectively ( P < 0.001), with corresponding median MAM of 4.7 mm and 0 mm, respectively ( P < 0.001). The area under the curve was higher for MAM quantified on intraprocedural CT (0.89; 95% confidence interval [CI], 0.83-0.94) compared with initial follow-up CT (0.66; 95% CI, 0.54-0.76) in predicting 1-year LTP ( P < 0.001). An MAM of 0 mm on intraprocedural CT was an independent predictor of LTP with a subdistribution hazards ratio of 11.9 (95% CI, 4.9-28.9; P < 0.001), compared with 2.4 (95% CI, 0.9-6.0; P = 0.07) on initial follow-up CT. CONCLUSIONS: Ablative margin quantified on intraprocedural CT significantly outperformed initial follow-up CT in predicting LTP and should be used for ablation endpoint assessment.

Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis.

BACKGROUND: Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity. METHODS: In this phase 1b study, registered at Clinical. TRIALS: gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). FINDINGS: The trial enrolled 23 patients: 18 with ovarian cancer, 2 with uterine cancer, and 3 with cervical cancer. Study evaluable patients (n = 16) received a median of 2 prior lines of therapy (range: 1-8). Partial response was observed in 2 patients (12.5%; 1 ovarian, 1 uterine), and complete response was observed in 1 patient (6.3%) with cervical cancer, for an ORR of 18.8% (95% confidence interval: 4.0%-45.6%). The median duration of response was 14.8 months (range: 4.1-20.8), with one complete response ongoing. Median PFS and OS were 2.7 months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. CONCLUSIONS: i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3 mg/kg i.p. nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks. FUNDING: This work was funded by Bristol Myers Squibb (CA209-9C7), an MD Anderson Cancer Center Support Grant (CA016672), the Ovarian Cancer Moon Shots Program, the Emerson Collective Fund, and a T32 training grant (CA101642).

Controlled Delivery of Rosuvastatin or Rapamycin through Electrospun Bismuth Nanoparticle-Infused Perivascular Wraps Promotes Arteriovenous Fistula Maturation.

In the context of arteriovenous fistula (AVF) failure, local delivery enables the release of higher concentrations of drugs that can suppress neointimal hyperplasia (NIH) while reducing systemic adverse effects. However, the radiolucency of polymeric delivery systems hinders long-term in vivo surveillance of safety and efficacy. We hypothesize that using a radiopaque perivascular wrap to deliver anti-NIH drugs could enhance AVF maturation. Through electrospinning, we fabricated multifunctional perivascular polycaprolactone (PCL) wraps loaded with bismuth nanoparticles (BiNPs) for enhanced radiologic visibility and drugs that can attenuate NIH─rosuvastatin (Rosu) and rapamycin (Rapa). The following groups were tested on the AVFs of a total of 24 Sprague-Dawley rats with induced chronic kidney disease: control (i.e., without wrap), PCL-Bi (i.e., wrap with BiNPs), PCL-Bi-Rosu, and PCL-Bi-Rapa. We found that BiNPs significantly improved the wraps' radiopacity without affecting biocompatibility. The drug release profiles of Rosu (hydrophilic drug) and Rapa (hydrophobic drug) differed significantly. Rosu demonstrated a burst release followed by gradual tapering over 8 weeks, while Rapa demonstrated a gradual release similar to that of the hydrophobic BiNPs. In vivo investigations revealed that both drug-loaded wraps can reduce vascular stenosis on ultrasonography and histomorphometry, as well as reduce [18F]Fluorodeoxyglucose uptake on positron emission tomography. Immunohistochemical studies revealed that PCL-Bi-Rosu primarily attenuated endothelial dysfunction and hypoxia in the neointimal layer, while PCL-Bi-Rapa modulated hypoxia, inflammation, and cellular proliferation across the whole outflow vein. In summary, the controlled delivery of drugs with different properties and mechanisms of action against NIH through a multifunctional, radiopaque perivascular wrap can improve imaging and histologic parameters of AVF maturation.