Safety and Efficacy of Percutaneous Cryoablation for Recurrent or Metastatic Soft Tissue Sarcoma in Adult Patients.

Background: Treatment options are limited in patients with recurrent or metastatic disease after initial treatment of soft tissue sarcoma (STS) by surgical resection, radiation, or systemic therapy. Percutaneous cryoablation may provide a complementary minimally invasive option in this setting. Objective: To assess the safety and efficacy of percutaneous cryoablation performed for local control of treatment-refractory recurrent or metastatic STS. Methods: This single-institution retrospective study included adult patients who underwent percutaneous cryoablation from March 2016 to April 2023 to achieve local control of recurrent or metastatic STS after earlier treatment (surgery, radiation, or chemotherapy). For each treated lesion, a single interventional radiologist re-reviewed intraprocedural images to assess for adequate coverage by the ice ball of the entire lesion and a ≥5-mm margin in all dimensions. Complications and outcomes were extracted from medical records. The primary endpoint for procedure efficacy was 1-year local progression-free survival. Results: The study included 141 patients (median age, 66 years; 90 female, 51 male) who underwent 217 cryoablation procedures to treat 250 recurrent or metastatic STS lesions. The most common STS histologic types were leiomyosarcoma (56/141) and liposarcoma (39/141). Lesions had a mean long-axis diameter of 2.0 cm (range, 0.4-11.0 cm). Adequate ice-ball coverage was achieved for 82% (204/250) of lesions. The complication rate was 2% (4/217), entailing three major complications and one minor complication. Patients' median post-ablation follow-up was 25 months (range, 3-80 months). Local progression-free survival was 86% at 1 year and 79% at 2 years. Chemotherapy-free survival was 45% at 1 year and 31% at 2 years. Overall survival (OS) was 89% at 1 year and 80% at 2 years. In Kaplan-Meier analysis, leiomyosarcoma, in comparison with liposarcoma, had significantly higher local progression-free survival, but no significant difference in OS. In multivariable analysis, factors independently associated with an increased risk for local progression included inadequate ice-ball coverage (HR=7.73) and a lesion location of peritoneum (HR=3.63) or retroperitoneum (HR=3.71) relative to lung. Conclusion: Percutaneous cryoablation has a favorable safety and efficacy profile in patients with recurrent or metastatic STS after earlier treatments. Clinical Impact: Percutaneous cryoablation should be considered for local control of treatment-refractory STS.

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.

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.

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).

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.

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.

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.

Bioresorbable Mesenchymal Stem Cell-Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia Following Arteriovenous Fistula Formation in a Rat Model of Chronic Kidney Disease.

Bioresorbable perivascular scaffolds loaded with antiproliferative agents have been shown to enhance arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). These scaffolds, which can mimic the three-dimensional architecture of the vascular extracellular matrix, also have an untapped potential for the local delivery of cell therapies against NIH. Hence, an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein is fabricated. Chronic kidney disease (CKD) in Sprague-Dawley rats is induced by performing 5/6th nephrectomy, then AVFs for scaffold application are created. The following groups of CKD rats are compared: no perivascular scaffold (i.e., control), PCL alone, and PCL+MSC scaffold. PCL and PCL+MSC significantly improve ultrasonographic (i.e., luminal diameter, wall-to-lumen ratio, and flow rate) and histologic (i.e., neointima-to-lumen ratio, neointima-to-media ratio) parameters compared to control, with PCL+MSC demonstrating further improvement in these parameters compared to PCL alone. Moreover, only PCL+MSC significantly reduces 18 F-fluorodeoxyglucose uptake on positron emission tomography. These findings suggest that adding MSCs promotes greater luminal expansion and potentially reduces the inflammatory process underlying NIH. The results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.

A novel method for predicting hepatocellular carcinoma response to chemoembolization using an intraprocedural CT hepatic arteriography-based enhancement mapping: a proof-of-concept analysis.

BACKGROUND: To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method. METHODS: This three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (TPost/pre-RE) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (TPost-RE > 1) versus non-residual (TPost-RE ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries. RESULTS: CTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on TPost-RE (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0-99.9) and specificity of 100% (95% CI, 87.2-100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE). CONCLUSION: CTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.

Fast-track two-stage hepatectomy by concurrent portal vein embolization at first-stage hepatectomy in hybrid interventional radiology / operating suite.

OBJECTIVES: In two-stage hepatectomy for bilateral liver metastases, patient dropout between stages is a major issue. We recently proposed a novel approach of fast-track two-staged hepatectomy (FT-TSH), in which patients undergo concurrent first-stage hepatectomy (FSH) with portal vein embolization (PVE) in a hybrid interventional radiology surgical suite. However, its efficacy remains unclear. METHODS: Patients with bilateral liver metastases scheduled for FT-TSH at MD Anderson Cancer Center between October 2017 and December 2020 were included on a prospective registry. The effectiveness and feasibility were evaluated. RESULTS: Nineteen patients were scheduled for FT-TSH. Primary site of tumor was colon/rectum in 18 patients and ovary in one patient. Median number of tumors was 10 and median size of largest tumor before surgery was 2.4 cm. Two (11%) patients did not undergo PVE and seventeen patients (89%) completed FSH + PVE. None of the patients had a major complication (Clavien-Dindo grade ≥ III) after FSH + PVE. Median kinetic growth rate after FSH + PVE was 2.9%/week (range 0.8-5.6). Twelve patients (71%) among the seventeen who underwent FSH + PVE proceeded to second-stage hepatectomy, and ten patients (59%) finally completed second-stage hepatectomy. Median interval between stages was 5.6 weeks (4.0-20.1). One patient (10%) had a major morbidity after SSH, and there was no 90-day mortality. CONCLUSIONS: FT-TSH is safe and allows for short intervals between hepatectomy stages while achieving favorable liver hypertrophy. Further investigation is needed to evaluate the true efficacy of FT-TSH.

Safety and efficacy of percutaneous transabdominal and transesophageal decompression gastric catheters for palliation of malignant bowel obstruction.

PURPOSE: To evaluate the safety and primary technical success rate of gastric decompression via percutaneous transabdominal gastrostomy (PTAG) or percutaneous transesophageal gastric (PTEG) catheter placement for management of malignant bowel obstruction (MBO). A secondary purpose was to evaluate the safety and success rate for PTAG catheter placement in patients with both MBO and ascites. METHODS: A single-institution retrospective review of 385 patients who underwent attempted decompression gastric catheter placement from March 2013 to August 2018 was performed. Medical records and imaging studies were reviewed. A subgroup of patients with concomitant MBO and ascites were identified. The primary outcome measures were procedural technical success and procedural complications. RESULTS: 394 decompression gastrostomy catheters were attempted from 2013 to 2018, n = 353 PTAG and n = 41 PTEG. The success rate was 95.5% (n = 337 of 353) for PTAG and 97.6% (n = 40 of 41) for PTEG. There were 63 total complications involving 47 (13.9%) patients following PTAG and 13 total complications involving 9 (22.5%) patients following PTEG, P = 0.16. For the subgroup of patients with MBO and ascites, the success rate was 94.8% (n = 182 of 192 patients), and there were 20 complications involving 17 (12.9%) of 132 patients. CONCLUSION: Gastric decompression for patients with MBO via PTAG or PTEG catheter placement is associated with high success rates and low complications.

Overall Body Composition and Sarcopenia Are Associated with Poor Liver Hypertrophy Following Portal Vein Embolization.

PURPOSE: To explore whether body composition and/or sarcopenia are associated with liver hypertrophy following portal vein embolization (PVE) in patients with colorectal liver metastases (CLM). METHODS: Patients with CLM who underwent right PVE prior to a planned right hepatectomy were identified from the institutional liver database from 2004 to 2014. Patients were excluded due to previous liver-directed therapy/hepatectomy, right PVE + segment IV embolization, or planned 2-stage hepatectomy. Advanced imaging software was used to measure body compartment volumes (cm2), which were standardized to height (m2) to create an index: skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). SMI, gender, and body mass index (BMI) were used to define sarcopenia. The main outcome of interest was hypertrophy of the future liver remnant (FLR) following PVE, which was reported as degree of hypertrophy (DH) and kinetic growth rate (KGR). RESULTS: Patients were evenly divided into three KGR groups: lower third (KGR:0.7-2.0%), middle third (KGR:2.0-4.1%), and upper third (KGR:4.2-12.3%). Patients in the lower third KGR group had a lower VAI (31.0 vs 53.0 vs 54.5 cm2/m2, p = 0.042) and were more commonly sarcopenic (60%) compared to the upper third (20%, p = 0.025). Eighteen patients (40%) met criteria for sarcopenia. Sarcopenic patients had a lower VAI (29.1 vs 57.4 cm2/m2, p = 0.004), lesser degree of hypertrophy (8.3% vs 15.2%, p = 0.009), and lower KGR (2.0% vs 4.0%, p = 0.012). CONCLUSION: Sarcopenia and associated body composition indices are strongly associated with clinically relevant impaired liver regeneration, which may result in increased liver-specific complications following hepatectomy for CLM.

Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors.

PURPOSE: Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation. PATIENTS AND METHODS: This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 6 dose cohorts (1 × 104 to 3 × 106 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose. RESULTS: Among 24 patients, a single intratumoral injection of C. novyi-NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses. The cohort 5 dose (1 × 106 spores) was defined as the maximum tolerated dose; DLTs were grade 4 sepsis (n = 2) and grade 4 gas gangrene (n = 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n = 1), limb abscess (n = 1), soft-tissue infection (n = 1), respiratory insufficiency (n = 1), and rash (n = 1), which occurred across four patients. Of 22 evaluable patients, nine (41%) had a decrease in size of the injected tumor and 19 (86%) had stable disease as the best overall response in injected and noninjected lesions combined. C. novyi-NT injection elicited a transient systemic cytokine response and enhanced systemic tumor-specific T-cell responses. CONCLUSIONS: Single intratumoral injection of C. novyi-NT is feasible. Toxicities can be significant but manageable. Signals of antitumor activity and the host immune response support additional studies of C. novyi-NT in humans.

A new sequential treatment strategy for multiple colorectal liver metastases: Planned incomplete resection and postoperative completion ablation for intentionally-untreated tumors under guidance of cross-sectional imaging.

PURPOSE: We retrospectively evaluated outcomes of a new sequential treatment strategy for patients with multiple colorectal liver metastases (CLM): planned incomplete resection and postoperative percutaneous completion ablation for intentionally-untreated lesions under cross-sectional imaging guidance. METHODS: Patients with CLM who underwent curative-intent hepatectomy and ablation during 2007-2018 were analyzed. Complications, local tumor progression (LTP) rates at ablation site(s), and overall survival (OS) estimated using the Kaplan-Meier method were compared between patients who underwent CLM resection and postoperative percutaneous ablation for intentionally-untreated lesions (completion ablation) and patients who underwent CLM resection and concomitant intraoperative CLM ablation under ultrasound guidance. RESULTS: Number and largest diameter of CLM and liver resection complexity did not differ significantly between the completion ablation (n = 23) and intraoperative ablation (n = 92) groups. Microwave (versus radiofrequency) ablation was used more frequently in the completion ablation group than in the intraoperative ablation group (61% [14/23] vs. 6% [6/92], P = 0.001). The complication rate after hepatectomy and ablation was significantly lower in the completion ablation group (21% [5/23] versus 48% [44/92], P = 0.033). No death was observed in either group. The 5-year LTP cumulative incidence was significantly lower in the completion ablation group (31.7% versus 62.4%, P = 0.030). The 5-year OS rate did not differ significantly between groups (53%, completion ablation; 42%, intraoperative ablation; P = 0.407). CONCLUSIONS: Resection and postoperative percutaneous completion ablation under cross-sectional imaging guidance may be a safe and effective treatment pathway in patients with CLM in whom liver resection alone cannot achieve R0 resection.

Association of Inferior Vena Cava Filter Placement With Rates of Pulmonary Embolism in Patients With Cancer and Acute Lower Extremity Deep Venous Thrombosis.

Importance: Venous thromboembolism is the second overall leading cause of death for patients with cancer, and there is an approximately 2-fold increase in fatal pulmonary embolism (PE) in patients with cancer. Inferior vena cava (IVC) filters are designed to prevent PE, but defining the appropriate use of IVC filters in patients with cancer remains a substantial unmet clinical need. Objective: To evaluate the association of IVC filters with the development of PE in patients with cancer and deep venous thrombosis (DVT). Design, Setting, and Participants: A population-based cohort study was conducted using administrative data on 88 585 patients from the state inpatient databases for California (2005-2011) and Florida (2005-2014). Based on diagnostic and procedure codes, patients with cancer and acute lower extremity DVT were identified. All subsequent hospital visits for these patients were evaluated for the placement of an IVC filter, the development of new PE, the development of new DVT, and in-hospital mortality. Data analysis was performed from September 1 to December 1, 2019. Exposures: Placement of an IVC filter. Main Outcomes and Measures: The association of IVC filter placement with rates of new PE and DVT was estimated using a propensity score matching algorithm and competing risk analysis. Results: The study cohort comprised 88 585 patients (45 074 male; median age, 71.0 years [range, 1.0-104.0 years]) with malignant neoplasms who presented to a health care institution with a diagnosis of acute lower extremity DVT. Of these patients, 33 740 (38.1%) underwent IVC filter placement; patients with risk factors such as upper gastrointestinal bleeding (odds ratio, 1.32; 95% CI, 1.29-1.37), intracranial hemorrhage (odds ratio, 1.21; 95% CI, 1.19-1.24), and coagulopathy (odds ratio, 1.09; 95% CI, 1.08-1.10) were more likely to receive an IVC filter. A total of 4492 patients (5.1%) developed a new PE after their initial DVT diagnosis. There was a significant improvement in PE-free survival for these patients compared with those who did not receive IVC filters across the full, unbalanced study cohort as well as after propensity score matching and competing risk analysis (hazard ratio, 0.69; 95% CI, 0.64-0.75; P < .001). Furthermore, IVC filter placement reduced the development of PE in patients with very high-risk malignant neoplasms (eg, pancreaticobiliary cancer), high-risk malignant neoplasms (eg, lung cancer), and low-risk malignant neoplasms (eg, prostate cancer). After accounting for anticoagulation use and imbalanced risk factors, IVC filter placement did not increase the risk of new DVT development. Conclusions and Relevance: This study suggests that, for patients with cancer and DVT and bleeding risk factors, IVC filter placement is associated with an increased rate of PE-free survival.

Durability of partial splenic artery embolization on platelet counts for cancer patients with hypersplenism-related thrombocytopenia.

PURPOSE: Partial splenic artery embolization (PSAE) has shown promise in increasing platelet counts in cancer patients with hypersplenism-related thrombocytopenia. The purpose of this study was to identify response predictors and to longitudinally evaluate PSAE efficacy and durability in a large cohort of cancer patients with hypersplenism-related thrombocytopenia. METHODS: A single-institution, IRB-approved, HIPAA-compliant retrospective review of all PSAEs for thrombocytopenia between 2012 and 2015 was performed. Patients were classified as complete responders (CR, no platelet value < 100 × 109/L following PSAE), partial responders (PR, initial increase in platelets but subsequent decrease in platelets < 100 × 109/L), and non-responders (NR, platelets never > 100 × 109/L following PSAE). RESULTS: Of the 98 patients included in the study, 58 had CR (59%), 28 had PR (29%), and 12 patients had NR (12%). The percent splenic tissue embolized was significantly greater in the CR group compared to the PR group (P = 0.001). The percent volume of splenic tissue embolized was linearly correlated with the magnitude of platelet increase without a minimum threshold. At least one line of chemotherapy was successfully restarted in 97% of patients, and 41% of patients did not experience recurrence of thrombocytopenia for the duration of their survival. The major complication rate was 8%, with readmission following initial hospitalization for persistent "post-embolization syndrome" symptoms the most common. CONCLUSIONS: In cancer patients with hypersplenism-related thrombocytopenia, PSAE is a safe intervention that effects a durable elevation in platelet counts across a range of malignancies and following the re-initiation of chemotherapy.

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%).

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.

Pulmonary Hemorrhage Following Percutaneous Computed Tomography-Guided Lung Biopsy: Retrospective Review of Risk Factors, Including Aspirin Usage.

BACKGROUND: To evaluate the significance of aspirin, as well as, other potential confounding risk factors, on the incidence and volume of pulmonary hemorrhage in patients undergoing percutaneous computed tomography-guided lung biopsy. METHODS: This retrospective study was approved by the institutional review board. Between September 2013 and December 2014, 252 patients taking aspirin underwent transthoracic computed tomography-guided lung biopsy. Patient, technical, and lesion-related risk factors were evaluated. Univariate analysis was performed with a Student's t test, chi-square test, or Fisher's exact test, as appropriate followed by multivariate logistic regression. RESULTS: Of 252 patients, 49 (19.4%) continued or stopped aspirin ≤4 days prior to biopsy and 203 (80.6%) patients stopped aspirin ≥5 days prior to biopsy. Pulmonary hemorrhage occurred in 174 cases (69.0%). The median volume of hemorrhage was 3.74 cm3 (range, 0-163.5 cm3). Multivariate analysis revealed that lesion size (P < 0.0001) and lesion depth (P < 0.0001) were independent risk factors for the incidence of pulmonary hemorrhage, while lesion size (P = 0.0035), transgression of intraparenchymal vessels (P < 0.0001), and lesion depth (P = 0.0047) were independent risk factors for severity of hemorrhage. Aspirin stopped ≤4 days from a percutaneous lung biopsy was not associated with pulmonary hemorrhage. CONCLUSION: Aspirin taken concurrently or stopped within 4 days of transthoracic lung biopsy is not an independent risk factor for pulmonary hemorrhage. The incidence of hemorrhage following lung biopsy is associated with lesion size and depth, while the severity of hemorrhage is associated with lesion size, depth, as well as traversal of intraparenchymal vessels.