Impact of Percutaneous Cryoablation on Renal Function in Patients with Stage I Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the effect of cryoablation on renal function (measured by eGFR or serum creatinine) for treating Stage I renal cancer. MATERIALS AND METHODS: MEDLINE, EMBASE, and the CENTRAL databases were systematically searched from inception to May 1, 2023. Cohort studies that included data on change of estimated glomerular filtration rate (eGFR) and serum creatinine increase were included. Meta-analysis was performed by measuring the weighted mean difference and by fitting random-effect models. RESULTS: Overall, 38 studies were included, comprising of 3,202 participants. Percutaneous cryoablation was associated with an absolute eGFFR reduction of -3.06 ml/min/1.73 m2 (95% CI: -4.12 to -2.01; p-value < 0.001) and serum creatinine increase of 0.05 mg/dl (95% CI: -0.02 to 0.11; p-value> 0.05). The weighted absolute mean difference of percutaneous cryoablation for treating stage T1b renal cell carcinoma was estimated at -5.19 ml/min/1.73 m2 (95% CI: -11.1 to 0.72; p-value > 0.05). Lastly, when analyzing studies that included cohorts with solitary kidneys, the pooled weighted mean difference was estimated as -3.27 ml/min/1.73 m2 (95% CI: -6.79 to 0.25; pvalue >0.05). CONCLUSIONS: Percutaneous cryoablation for Stage 1 renal cell carcinoma has minimal significant impact on renal function (measured by eGFR or serum creatinine). The same outcome was observed in patients with larger tumors (T1b) and those with solitary kidneys.

Outcomes of Repeat Conventional Transarterial Chemoembolization in Patients with Liver Metastases.

INTRODUCTION AND OBJECTIVES: Although unlimited sessions of conventional transarterial chemoembolization (cTACE) may be performed for liver metastases, there is no data indicating when treatment becomes ineffective. This study aimed to determine the optimal number of repeat cTACE sessions for nonresponding patients before abandoning cTACE in patients with liver metastases. MATERIALS AND METHODS: In this retrospective, single-institutional analysis, patients with liver metastases from neuroendocrine tumors (NET), colorectal carcinoma (CRC), and lung cancer who underwent consecutive cTACE sessions from 2001 to 2015 were studied. Quantitative European Association for Study of the Liver (qEASL) criteria were utilized for response assessment. The association between the number of cTACE and 2-year, 5-year, and overall survival was evaluated to estimate the optimal number of cTACE for each survival outcome. RESULTS: Eighty-five patients underwent a total of 186 cTACE sessions for 117 liver metastases, of which 30.7% responded to the first cTACE. For the target lesions that did not respond to the first, second, and third cTACE sessions, response rates after the second, third, and fourth cTACE sessions were 33.3%, 23%, and 25%, respectively. The fourth cTACE session was the optimal number for 2-year survival (HR 0.40; 95%CI: 0.16-0.97; p=0.04), 5-year survival (HR 0.31; 95%CI: 0.11-0.87; p=0.02), and overall survival (HR 0.35; 95%CI: 0.13-0.89; p=0.02). CONCLUSIONS: Repeat cTACE in the management of liver metastases from NET, CRC, and lung cancer was associated with improved patient survival. We recommend at least four cTACE sessions before switching to another treatment for nonresponding metastatic liver lesions.

Quaternary nanoparticles enable sustained release of bortezomib for hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related mortality in the world. Over the past two decades, there has been minimal improvement in therapies as well as clinical outcomes for patients with Barcelona Clinic Liver Cancer (BCLC)-B. These patients are treated with local interventions, including transarterial chemoembolization. Current methodologies only allow sustained intratumoral release measured in hours. Methodologies to allow sustained local release of the drug cargo over days to weeks are acutely needed. We hypothesize that tumor response as well as outcomes of patients with BCLC-B can be improved through utilization of a highly cytotoxic agent delivered with a sustained release platform. APPROACH AND RESULTS: High-throughput drug screening across 40 HCC patient-derived organoids identified bortezomib (BTZ) as a highly cytotoxic small molecule for HCC. We designed and manufactured sustained release BTZ nanoparticles (BTZ-NP) using a flash nanocomplexation/nanoprecipitation process. We quantified the release profile and tested the anti-tumoral effects in vivo. The BTZ-NP formulation demonstrated a sustained release of BTZ of 30 days. This BTZ-NP formulation was highly effective in controlling tumor size and improved survival in vivo in three animal models of HCC, including when delivered via the hepatic artery, as we envision its delivery in patients. In addition, the BTZ-NP formulation was superior to treatment with doxorubicin-drug eluting beads. CONCLUSIONS: The BTZ-NP formulation provides a potent and safe treatment of HCC via a localized delivery approach. These results warrant additional preclinical studies to advance this technology to human clinical trials.

Optimization of the BCLC Staging System for Locoregional Therapy for Hepatocellular Carcinoma by Using Quantitative Tumor Burden Imaging Biomarkers at MRI.

Background Patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC) represent a highly heterogeneous patient collective with substantial differences in overall survival. Purpose To evaluate enhancing tumor volume (ETV) and enhancing tumor burden (ETB) as new criteria within the Barcelona Clinic Liver Cancer (BCLC) staging system for optimized allocation of patients with intermediate- and advanced-stage HCC to undergo transarterial chemoembolization (TACE). Materials and Methods In this retrospective study, 682 patients with HCC who underwent conventional TACE or TACE with drug-eluting beads from January 2000 to December 2014 were evaluated. Quantitative three-dimensional analysis of contrast-enhanced MRI was performed to determine thresholds of ETV and ETB (ratio of ETV to normal liver volume). Patients with ETV below 65 cm3 or ETB below 4% were reassigned to BCLC Bn, whereas patients with ETV or ETB above the determined cutoffs were restratified or remained in BCLC Cn by means of stepwise verification of the median overall survival (mOS). Results This study included 494 patients (median age, 62 years [IQR, 56-71 years]; 401 men). Originally, 123 patients were classified as BCLC B with mOS of 24.3 months (95% CI: 21.4, 32.9) and 371 patients as BCLC C with mOS of 11.9 months (95% CI: 10.5, 14.8). The mOS of all included patients (including the BCLC B and C groups) was 15 months (95% CI: 12.3, 17.2). A total of 152 patients with BCLC C tumors were restratified into a new BCLC Bn class, in which the mOS was then 25.1 months (95% CI: 21.8, 29.7; P < .001). The mOS of the remaining patients (ie, BCLC Cn group) (n = 222; ETV ≥65 cm3 or ETB ≥4%) was 8.4 months (95% CI: 6.1, 11.2). Conclusion Substratification of patients with intermediate- and advanced-stage hepatocellular carcinoma according to three-dimensional quantitative tumor burden identified patients with a survival benefit from transarterial chemoembolization before therapy. © RSNA, 2022 Online supplemental material is available for this article.

CT-Guided Celiac Ganglion Block for Neurogenic Gastrointestinal Dysmotility.

PURPOSE: To determine whether celiac ganglion block can serve as a diagnostic test for dysautonomia as the cause of gastrointestinal dysmotility-related symptoms. MATERIALS AND METHODS: This was an institutional review board-approved, prospective, single-arm, registered study, from January 2020 to May 2021, and included patients aged 14-85 years with gastrointestinal symptoms of food intolerance, abdominal pain, or angina. Patients with nonneurogenic causes (ie, chronic cholecystitis, peptic ulcer disease, gastroesophageal reflux, and malabsorption syndrome) were excluded. All 15 patients underwent computed tomography-guided celiac ganglion block with 100 mg of liposomal bupivacaine. Patients filled out the dysautonomia-validated questionnaire Composite Autonomic Symptom Score 31 (COMPASS-31) before and after intervention. Differences (before vs after) were compared with the exact permutation method. RESULTS: Fifteen women (median age, 17 years; range, 14-41 years) were included. Average COMPASS-31 score improved significantly, from baseline 11 (SD ± 2.8) to 4 (SD ± 1.9) (improvement, 7 points ± 2.8; P < .001). All patients reported significant reduction in abdominal angina. Fourteen of the 15 patients (93%) reported complete resolution, and 14 of 15 (93%) reported a significant reduction in non-postprandial abdominal pain (P < .01). Only 1 patient reported no improvement. Eight of those 14 patients (57%) reported complete resolution of abdominal pain. There was a significant improvement in functional scores (vomiting, P = .01; constipation frequency, P = .02; constipation severity, P < .01; and nausea, P < .01). The rate of minor and major adverse events was 13% and 0%, respectively, per the Society of Interventional Radiology adverse event classification. CONCLUSIONS: Celiac ganglion block is a safe diagnostic tool for confirming dysautonomia as the underlying condition in patients with gastrointestinal dysmotility-related symptoms. It could provide early diagnosis, lead to definitive treatment (ganglionectomy) earlier, or obviate unnecessary surgery.

Radiofrequency Ablation versus Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: An Analysis of the Scientific Registry of Transplant Recipients.

PURPOSE: To evaluate differences in waitlist mortality and dropout in liver transplant candidates with hepatocellular carcinoma (HCC) who undergo radiofrequency (RF) ablation versus transarterial chemoembolization (TACE). MATERIAL AND METHODS: From 2004 to 2013, 11,824 patients with HCC in the Scientific Registry of Transplant Recipients who underwent RF ablation or TACE were included and followed until December 31, 2019, or 5 years, whichever came first, and were stratified by the Milan criteria. Competing risk and Cox regression analyses to compare waitlist mortality and dropout were performed using adjusted hazard ratios (asHRs, with RF ablation group as reference). Regression models were adjusted for age, race, sex, calculated Model for End-Stage Liver Disease score, tumor size, and number. RESULTS: There was no difference in waitlist mortality and dropout for patients outside the Milan criteria (n = 1,226) who underwent TACE (19.2%) or RF ablation (19.0%) (asHR, 0.91; 95% CI, 0.79-1.03). There was also no difference for patients inside the Milan criteria (n = 10,598) in waitlist mortality/dropout (TACE 13.4% vs RF ablation 12.9%) (asHR, 1.29; 95% CI, 0.79-2.09). A subgroup analysis within the Milan criteria demonstrated no difference between TACE and RF ablation treatments in patients with a single tumor of ≤3 cm (asHR, 0.92; 95% CI, 0.77-1.10), with a single tumor of >3 cm (asHR, 1.03; 95% CI, 0.79-1.34), or with >1 tumor (asHR, 0.89; 95% CI, 0.72-1.09). CONCLUSIONS: Using the national registry data, no difference was found in waitlist mortality and dropout for transplant candidates with HCC who received TACE versus RF ablation.

Incidence and Contemporary Management of Delayed Bleeding Following Pancreaticoduodenectomy.

BACKGROUND: Delayed bleeding after pancreaticoduodenectomy (PD) is a life-threatening complication. However, the optimal management remains unclear. We summarize our experience of the management of delayed bleeding after PD and define the outcomes associated with different types of management. METHODS: All patients who underwent a PD between January 1987 and June 2020 at Johns Hopkins University were retrospectively reviewed. Delayed bleeding was defined as bleeding on or after postoperative day 5 following PD. Incidence, outcomes, and trends were reported. RESULTS: Among the 6201 patients that underwent PD, delayed bleeding occurred in 130 (2.1%) at a median of 12 days (IQR: 9, 24) postoperation. The pattern of bleeding was classified as intraluminal (51.5%), extraluminal (40.8%), and mixed (7.7%). A clinically relevant postoperative pancreatic fistula and an intraabdominal abscess preceded the delayed bleeding in 43.1% and 31.5% of cases, respectively. Arterial pseudoaneurysm or bleeding from peripancreatic vessels was the most common reason (54.6%) with the gastroduodenal artery being the most common source (18.5%). Endoscopy, angiography, and reoperation were performed as a first-line approach in 35.4%, 52.3%, and 6.2% of patients, respectively. The overall mortality was 16.2% and decreased over the study period (p < 0.01). CONCLUSIONS: Delayed bleeding following PD remains a life-threatening complication. The most common location of delayed bleeding is from the gastroduodenal artery. Angiography with embolization should be the initial approach for urgent bleeding with surgical re-exploration reserved for unstable patients or failed control of bleeding after interventional angiography or endoscopy.

Development, Practice Patterns, and Early Clinical Outcomes of a Multidisciplinary Liver Cancer Clinic.

Multidisciplinary care has been associated with improved survival in patients with primary liver cancers. We report the practice patterns and real world clinical outcomes for patients presenting to the Johns Hopkins Hospital (JHH) multidisciplinary liver clinic (MDLC). We analyzed hepatocellular carcinoma (HCC, n = 100) and biliary tract cancer (BTC, n = 76) patients evaluated at the JHH MDLC in 2019. We describe the conduct of the clinic, consensus decisions for patient management based on stage categories, and describe treatment approaches and outcomes based on these categories. We describe subclassification of BCLC stage C into 2 parts, and subclassification of cholangiocarcinoma into 4 stages. A treatment consensus was finalized on the day of MDLC for the majority of patients (89% in HCC, 87% in BTC), with high adherence to MDLC recommendations (91% in HCC, 100% in BTC). Among patients presenting for a second opinion regarding management, 28% of HCC and 31% of BTC patients were given new therapeutic recommendations. For HCC patients, at a median follow up of 11.7 months (0.7-19.4 months), median OS was not reached in BCLC A and B patients. In BTC patients, at a median follow up of 14.2 months (0.9-21.1 months) the median OS was not reached in patients with resectable or borderline resectable disease, and was 11.9 months in patients with unresectable or metastatic disease. Coordinated expert multidisciplinary care is feasible for primary liver cancers with high adherence to recommendations and a change in treatment for a sizeable minority of patients.

Identifying enhancement-based staging markers on baseline MRI in patients with colorectal cancer liver metastases undergoing intra-arterial tumor therapy.

OBJECTIVES: To determine if three-dimensional whole liver and baseline tumor enhancement features on MRI can serve as staging biomarkers and help predict survival of patients with colorectal cancer liver metastases (CRCLM) more accurately than one-dimensional and non-enhancement-based features. METHODS: This retrospective study included 88 patients with CRCLM, treated with transarterial chemoembolization or Y90 transarterial radioembolization between 2001 and 2014. Semi-automated segmentations of up to three dominant lesions were performed on pre-treatment MRI to calculate total tumor volume (TTV) and total liver volumes (TLV). Quantitative 3D analysis was performed to calculate enhancing tumor volume (ETV), enhancing tumor burden (ETB, calculated as ETV/TLV), enhancing liver volume (ELV), and enhancing liver burden (ELB, calculated as ELV/TLV). Overall and enhancing tumor diameters were also measured. A modified Kaplan-Meier method was used to determine appropriate cutoff values for each metric. The predictive value of each parameter was assessed by Kaplan-Meier survival curves and univariable and multivariable cox proportional hazard models. RESULTS: All methods except whole liver (ELB, ELV) and one-dimensional/non-enhancement-based methods were independent predictors of survival. Multivariable analysis showed a HR of 2.1 (95% CI 1.3-3.4, p = 0.004) for enhancing tumor diameter, HR 1.7 (95% CI 1.1-2.8, p = 0.04) for TTV, HR 2.3 (95% CI 1.4-3.9, p < 0.001) for ETV, and HR 2.4 (95% CI 1.4-4.0, p = 0.001) for ETB. CONCLUSIONS: Tumor enhancement of CRCLM on baseline MRI is strongly associated with patient survival after intra-arterial therapy, suggesting that enhancing tumor volume and enhancing tumor burden are better prognostic indicators than non-enhancement-based and one-dimensional-based markers. KEY POINTS: • Tumor enhancement of colorectal cancer liver metastases on MRI prior to treatment with intra-arterial therapies is strongly associated with patient survival. • Three-dimensional, enhancement-based imaging biomarkers such as enhancing tumor volume and enhancing tumor burden may serve as the basis of a novel prognostic staging system for patients with liver-dominant colorectal cancer metastases.

Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma with Intra-atrial Tumor Extension: Imaging Response and Oncologic Outcomes.

To evaluate outcomes in patients with right atrial (RA) hepatocellular carcinoma extension treated with transarterial chemoembolization. Eight patients were retrospectively reviewed. Follow-up visits occurred at 4-6 weeks; transarterial chemoembolization was repeated if residual tumor persisted. After transarterial chemoembolization, RA tumor volume reduction was 86% ± 19; α-fetoprotein level showed a reduction of 95%. From RA tumor diagnosis, 3-, 6-, and 12-month overall survival was 100% ± 0, 100% ± 0, and 67% ± 29, respectively. In patients with hepatocellular carcinoma invading the right atrium, transarterial chemoembolization alone or in combination with systemic therapy yields an improved imaging response and may be associated with improved survival.

Percutaneous Cryoablation for Stage 1 Renal Cell Carcinoma: Outcomes from a 10-year Prospective Study and Comparison with Matched Cohorts from the National Cancer Database.

Background Percutaneous cryoablation (PCA) is an increasingly utilized treatment for stage I renal cell carcinoma (RCC), albeit without supportive level I evidence. Purpose Primary objective was to determine the 10-year oncologic outcomes of PCA for stage I RCC in a prospective manner. Secondary objectives were to compare outcomes after partial nephrectomy (PN) and radical nephrectomy (RN) from the National Cancer Database (NCDB), to determine long-term renal function, and to determine the risk of metachronous disease. Materials and Methods In this institutional review board-approved prospective observational study (2006-2013), study participants with single, sporadic, biopsy-proven RCC were included to calculate the 10-year overall survival, recurrence-free survival, and disease-specific survival after PCA. Results were compared with matched PN and RN NCDB cohorts. Overall and recurrence-free survival probabilities were estimated by using nonparametric maximum likelihood estimator. Disease-specific survival was estimated by using the redistribution-to-right method. Age at diagnosis was stratified as a risk for survival. The effect on estimated glomerular filtration rate, serum creatinine level, and the risk for hemodialysis and metachronous disease were calculated. Results One hundred thirty-four patients (46% men) with single, sporadic, biopsy-proven RCC (median size ± standard deviation, 2.8 cm ± 1.4) were included. Overall survival was 86% (95% confidence interval [CI]: 80%, 93%) and 72% (95% CI: 62%, 83%), recurrence-free survival was 85% (95% CI: 79%, 91%) and 69% (95% CI: 59%, 79%) (improved over surgery), and disease-specific survival was 94% (95% CI: 90%, 98%) at both 5 years and 10 years (similar to surgery), respectively. The 10-year risk of hemodialysis was 2.3%. Risk of metachronous RCC was 6%. Charlson/Deyo Combined Comorbidity score analysis showed decreasing overall survival with increasing comorbidity index. The PCA cohort outperformed both RN- and PN-matched subgroups in all Charlson/Deyo Combined Comorbidity score categories. Conclusion Percutaneous cryoablation yielded a 10-year disease-specific survival of 94%, equivalent to that reported after radical or partial nephrectomy. Overall survival probability after percutaneous cryoablation at 5 years and 10 years was longer than for radical or partial nephrectomy, especially for patients at higher risk (Charlson/Deyo Combined Comorbidity score ≥2). © RSNA, 2020.

Irinotecan-Eluting 75-150-µm Embolics Lobar Chemoembolization in Patients with Colorectal Cancer Liver Metastases: A Prospective Single-Center Phase I Study.

PURPOSE: The primary end point of this trial was to determine the feasibility and safety of transarterial chemoembolization with the use of 75-150-µm drug-eluting embolics loaded with irinotecan (DEE-IRI) for the treatment of metastatic colorectal cancer (CRC) refractory to systemic chemotherapy. MATERIALS AND METHODS: Fourteen patients (mean age 57.9 years) with liver-dominant metastatic disease (14.3% unilobar, 85.7% bilobar), who had failed at least 1 line of chemotherapy, were enrolled and received up to 4 (mean 2.3) cycles of DEE-IRI lobar transarterial chemoembolization. Technical complications and adverse events were recorded, and response was assessed by means of imaging-based criteria. Levels of irinotecan and angiogenesis biomarkers in the serum were measured at multiple time points. RESULTS: Thirty-two DEE-IRI transarterial chemoembolizations were successfully performed, and the full dose (100 mg) was delivered in all cases. The only grade 3-4 toxicity was abdominal pain (29%). One patient had objective response according to the Response Evaluation Criteria in Solid Tumors and World Health Organization, and 3 patients had objective response according to the European Association for the Study of the Liver. The median overall survival was 18.14 months, and the 1-year survival was 65%. The average plasma Cmax of the active metabolite was 41.5 ± 26.1 ng/mL, with average Tmax of 1.3 ± 0.5 hours. The treatment significantly reduced levels of vascular endothelial growth factor receptor 1 (VEGFR1) at 24 hours. CONCLUSIONS: Lobar transarterial chemoembolization with the use of DEE-IRI is a technically feasible and well tolerated palliative treatment for patients with refractory liver-predominant CRC metastatic disease and has acceptable pharmacokinetics. VEGFR1 is a potential biomarker for predicting treatment efficacy and risk of adverse events.

Clinicopathological Distinction of Low-AFP-Secreting vs. High-AFP-Secreting Hepatocellular Carcinomas.

Ilntroduction and aims. We aimed to investigate the clinical and pathological differences between low-AFP-secreting (AFP < 20 ng/mL) and high-AFP-secreting (AFP ≥ 20 ng/mL) hepatocellular carcinomas in patients who undergo liver transplant (LT). MATERIAL AND METHODS: We evaluated 145 patients who underwent deceased donor LT for HCC from January 1, 2005 until August 1, 2015 at the Johns Hopkins Hospital. RESULTS: Median pre-LT AFP in the entire cohort was 13 ng/mL (IQR 6-59). Using serum AFP cutoff of 20 ng/mL, 61 (42%) patients had high-AFP-secreting tumors and 84 (58%) had low-AFP-secreting tumors. Patients with high-AFP-secreting tumors had larger lesions (3 cm vs. 2.4 cm, p = 0.024), and were more likely to have microvascular-invasion (36.1% vs. 20.2%, p = 0.02) and poor-differentiation (18% vs. 4.8%, p = 0.01), and tumor recurrence following LT (28% vs. 6%, p < 0.001). The 1-year, 3-year, and 5-year recurrence-free survival for patients in the low-AFP-secreting group compared to the high-AFP-secreting group were 100%, 92%, 92% vs. 81.3%, 71.3%, 68.5% respectively (p = 0.0003). CONCLUSION: AFP is a suboptimal predictor of tumor recurrence following liver transplant in HCC patients. However, it can have some value in distinguishing more aggressive forms of HCC (high-AFP-secreting) that are associated with higher tumor recurrence. Novel tumor biomarkers are needed that can enhance predicting tumor recurrence following LT based on tumor biology.

Elucidation of Percutaneously Accessible Lymph Nodes in Swine: A Large Animal Model for Interventional Lymphatic Research.

PURPOSE: To define percutaneously accessible, anatomically reproducible swine lymph nodes using magnetic resonance imaging, ultrasound, and ethiodized oil (Lipiodol; Guerbet, Bloomington, Indiana) lymphangiography. MATERIALS AND METHODS: Five adult female swine (Yorkshire, 50-60 kg) were used. Under general anesthesia, T1-weighted and T2-weighted, coronal and axial images of the entire swine were obtained. The animal's extrathoracic, extraperitoneal soft tissues from the neck to the groins were examined with ultrasound. Lymph nodes ≥ 1 cm were marked before the animal was transferred to the angiography suite. Under ultrasound guidance, the nodes were accessed, and lymphangiograms were obtained. The imaging findings between the 3 modalities were correlated, and the lymph node drainage was mapped. RESULTS: Four lymph nodes/lymph node groups were identified that were reproducible in all 5 animals, > 1 cm and percutaneously accessible: submandibular node, superficial cervical lymph node group, subiliac node, and superficial inguinal lymph node group. Drainage of these nodes mirrored human anatomy. The abdominopelvic lymphatics formed a retroperitoneal cisterna chyli and drained cephalad via a thoracic duct. CONCLUSIONS: The swine exhibits reproducible lymphatic anatomy with at least 4 percutaneously accessible lymph nodes/lymph node groups. Based on these results, the swine may be a suitable large animal model for research into lymphatic interventions.