Microwave ablation for hepatic malignancies: a systematic review of the technology and differences in devices.

BACKGROUND: Microwave ablation (MWA) has become the standard thermal-based treatment for hepatic malignancies in patients who have unresectable disease based on the biology of the tumor, the patients' comorbidities, and certain disease sites. The technical effectiveness, ablation success, local recurrence rates of hepatic malignancies treated with the various commercial microwave ablation devices has not been previously published in the peer reviewed literature. The aim of this systematic review is to summarize the clinical outcomes for the various MWA devices in the use of a hepatic malignancies to best educate hepatic surgeons as well as interventional radiologists. METHODS: A comprehensive review of the literature and instructions for use of each device that was published from 1/2013 to 12/2020 was performed. The main outcomes extracted were technical success, ablation success, major complications, local and new recurrence rates, recurrence-free survival, ablation volumes, time, and the number of antennas required. A qualitative review of the literature was performed. RESULTS: In total, 29 studies reporting data on 3250 patients and 4500 tumors were included in this review. Median patient age was 60.5 years (range 3-91). 76.3% (2420 M/753 F) of patients were male. Hepatocellular carcinoma (55%) was the most common tumor pathology followed by colorectal liver metastasis (10%) and cholangiocarcinoma (4%). A majority of studies reported technical success (range, 91.6-100%) and ablation success (range, 73.1-100%), as well as major complications (range, 0-9.1%). Local recurrence (range, 0-50%) was reported by 21 of the studies; however, new recurrence (range, 12.2-64%) was reported less frequently (6 studies) and were further specified in 12, six, and four studies as intrahepatic distant recurrence (11.3-54.2%), extrahepatic distant recurrence (3.6-20%), and metastasis (1.1-36%). A total of three, six, and five studies report disease, progression, and recurrence-free survival rates, respectively. CONCLUSION: Microwave ablation is frequently used for the treatment of hepatic malignancies. A thorough understanding of the clinical outcomes associated with different pathologies and MWA devices can improve surgeon awareness and help prepare for operative planning and patient management. More consistent reporting of key outcomes in the literature is needed to achieve such an understanding.

Preventing Futile Liver Resection: A Risk-Based Approach to Surgical Selection in Major Hepatectomy for Colorectal Cancer.

BACKGROUND: Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy. METHODS: Sequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy). RESULTS: Of 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1-16.2) for the futile resection cohort versus 45.6 (95% CI 39.1-52.1) for non-futile hepatectomies (p < 0.001). CONCLUSIONS: Futile hepatic resection can be predicted based on preoperative factors and carries a poor prognosis. Improved risk stratification for futility will aid in patient selection and treatment discussions.

The Weight of Nutrition on Post-Resection Oncologic Morbidity and Mortality: A Systematic Review and Meta-Analysis of Nutritional Indices.

CONTEXT: Nutritional status is a critical factor in the selection of patients for solid tumor resection. A variety of indices have been developed to quantify nutritional status, and they have differing degrees of predictive power for various postoperative outcomes. OBJECTIVE: This study aimed to comprehensively evaluate the predictive ability of commonly used nutritional indices in relation to postoperative complications (POCs), recurrence-free survival (RFS), and OS. DATA SOURCES: We performed a systematic review of 14 established nutritional indices from January 2015 to July 2022. DATA EXTRACTION: The primary end point was OS, while the secondary end points were POCs and RFS. A subsequent meta-analysis was performed to further assess the predictive ability of these indices for OS based on general index type, primary tumor site, and the patient's index status. DATA ANALYSIS: In this evaluation, 38 articles reporting data on 23 970 patients were analyzed, focusing on 14 nutritional indices. The indices were categorized into phenotypic, metabolic, immunologic, and combined types. Patients within the cut-off range of any index were predicted to have lower OS (hazard ratio [HR] 2.14, 95% CI 1.84-2.49, P < .01). Lower gastrointestinal (GI) and "other" sites were less predictive than upper GI primary tumors (HR 1.63, HR 1.82, and HR 2.54, respectively; all with P < .01). Phenotypic indices were less predictive than combined indices (HR 1.73 vs HR 2.47, P < .01). Within the combined category, there was no significant difference in the predictive ability of Prognostic Nutritional Index (PNI) vs Geriatric Nutritional Risk Index (GNRI) vs Controlling Nutritional Index (CONUT) (HR 2.63 vs HR 2.42 vs HR 2.07, P = .07). CONCLUSION: The predictive efficacy of a nutritional index was found to be highly dependent on the index type, the primary tumor site, and the outcome of interest. In the context of upper GI resections, nutritional status appeared to be more of a significant predictor of OS, compared with cases involving lower GI and hepatic malignancies. Indices that integrate phenotypic, metabolic, and immunologic patient factors potentially offer greater clinical utility in forecasting OS.

Consensus Guidelines of Irreversible Electroporation for Pancreatic Tumors: Protocol Standardization Using the Modified Delphi Technique.

Since no uniform treatment protocol for pancreatic irreversible electroporation (IRE) exists, the heterogeneity throughout literature complicates the comparison of results. To reach agreement among experts, a consensus study was performed. Eleven experts, recruited according to predefined criteria regarding previous IRE publications, participated anonymously in three rounds of questionnaires according to a modified Delphi technique. Consensus was defined as having reached ≥80% agreement. Response rates were 100, 64, and 64% in rounds 1 to 3, respectively; consensus was reached in 93%. Pancreatic IRE should be considered for stage III pancreatic cancer and inoperable recurrent disease after previous local treatment. Absolute contraindications are ventricular arrhythmias, implantable stimulation devices, congestive heart failure NYHA class 4, and severe ascites. The inter-electrode distance should be 10 to 20 mm and the exposure length should be 15 mm. After 10 test pulses, 90 treatment pulses of 1,500 V/cm should be delivered continuously, with a 90-µs pulse length. The first postprocedural contrast-enhanced computed tomography should take place 1 month post-IRE, and then every 3 months. This article provides expert recommendations regarding patient selection, procedure, and follow-up for IRE treatment in pancreatic malignancies through a modified Delphi consensus study. Future studies should define the maximum tumor diameter, response evaluation criteria, and the optimal number of preoperative FOLFIRINOX cycles.

The induction of peripheral trained immunity in the pancreas incites anti-tumor activity to control pancreatic cancer progression.

Despite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate ß-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, ß-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer.

Drug-eluting bead therapy in primary and metastatic disease of the liver.

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) is a novel therapy for the treatment of hypervascuarized tumours. Through the intra-arterial delivery of microspheres, DEB-TACE allows for embolization as well as local release of chemotherapy in the treatment of hepatic malignancy, providing an alternative therapeutic option in unresectable tumours. Its role as an adjunct to surgical resection or radiofrequency ablation (RFA) is less clear. The purpose of this review is to summarize recent studies investigating DEB-TACE in order to better define safety, efficacy and outcomes associated with its use. METHODS: A systematic review of all published articles and trials identified nine clinical trials and 23 abstracts. These were reviewed for tumour histology, stage of treatment, delivery technique, outcome at follow-up, complications and mortality rates. RESULTS: Publications involved treatment of hepatocellular carcinoma (HCC), metastatic colorectal carcinoma (MCRC), metastatic neuroendocrine (MNE) disease and cholangiocarcinoma (CCA). Using Response Evaluation Criteria in Solid Tumours (RECIST) or European Association for the Study of the Liver (EASL) criteria, studies treating HCC reported complete response (CR) rates of 5% (5/101) at 1 month, 9% (8/91) at 4 months, 14% (19/138) at 6 months and 25% (2/8) at 10 months. Partial response (PR) was reported as 58% (76/131) at 1 month, 50% (67/119) at 4 months, 57% (62/108) at 6-7 months and 63% (5/8) at 10 months. Studies involving MCRC, CCA and MNE disease were less valuable in terms of response rate because there is a lack of comparative data. The most common procedure-associated complications included fever (46-72%), nausea and vomiting (42-47%), abdominal pain (44-80%) and liver abscess (2-3%). Rather than reporting individual symptoms, two studies reported rates of post-embolic syndrome (PES), consisting of fever, abdominal pain, and nausea and vomiting, at 82% (75/91). Six of eight studies reported length of hospital stay, which averaged 2.3 days per procedure. Mortality was reported as occurring in 10 of 456 (2%) procedures, or 10 of 214 (5%) patients. CONCLUSIONS: Drug-eluting bead TACE is becoming more widely utilized in primary and liver-dominant metastatic disease of the liver. Outcomes of success must be expanded beyond response rates because these are not a reliable surrogate for progression-free survival or overall survival. Ongoing clinical trials will further clarify the optimal timing and strategy of this technology.