Prejesh Philips

Irreversible Electroporation Ablation (IRE) of Unresectable Soft Tissue Tumors: Learning Curve Evaluation in the First 150 Patients Treated

Background Irreversible electroporation (IRE) is a novel technology that uses peri-target discrete probes to deliver high-voltage localized electric current to induce cell death without thermal-induced coagulative necrosis. “Learnability” and consistently effective results by novice practitioners is essential for determining acceptance of novel techniques. This multi-center prospectively-collected database study evaluates the learning curve of IRE. Methods Analysis of 150 consecutive patients over 7 institutions from 9/2010-7/2012 was performed with patients treated divided into 3 groups A (1st 50 patients treated), B (2nd 50) and C (3rd 50 patients treated) chronologically and analyzed for outcomes. Results A total of 167 IRE procedures were performed, with a majority being liver(39.5%) and pancreatic(35.5%) lesions. The three groups were similar with respect to co-morbidities and demographics. Group C had larger lesions (3.9vs3cm,p=0.001), more numerous lesions (3.2vs2.2,p=0.07), more vascular invasion(p=0.001), underwent more associated procedures(p=0.001) and had longer operative times(p<0.001). Despite this, they had similar complication and high-grade complication rates(p=0.24). Attributable morbidity rate was 13.3%(total 29.3%) and high-grade complications were seen in 4.19%(total 12.6%). Pancreatic lesions(p=0.001) and laparotomy(p=0.001) were associated with complications. Conclusion The review represents that single largest review of IRE soft tissue ablation demonstrating initial patient selection and safety. Over time, complex treatments of larger lesions and lesions with greater vascular involvement were performed without a significant increase in adverse effects or impact on local relapse free survival. This evolution demonstrates the safety profile of IRE and speed of graduation to more complex lesions, which was greater than 5 cases by institution. IRE is a safe and effective alternative to conventional ablation with a demonstrable learning curve of at least 5 cases to become proficient.

Evaluation of resistance as a measure of successful tumor ablation during irreversible electroporation of the pancreas.

BACKGROUND Intraoperative evaluation of successful pancreatic tumor ablation using irreversible electroporation (IRE) is difficult secondary to lack of visual confirmation. The IRE generator provides feedback by reporting current (amperage), which can be used to calculate changes in tumor tissue resistance. The purpose of the study was to determine if resistance can be used to predict successful tumor ablation during IRE for pancreatic cancers. STUDY DESIGN All patients undergoing pancreatic IRE from March 2010 to December 2012 were evaluated using a prospective database. Intraoperative information, including change in tumor resistance during ablation and slope of the resistance curve, were used to evaluate effectiveness of tumor ablation in terms of local failure or recurrence (LFR) and disease-free survival (DFS). RESULTS A total of 65 patients underwent IRE for locally advanced pancreatic cancer. Median follow-up was 23 months. Local failure or recurrence was seen in 17 patients at 3, 6, or 9 months post IRE. Change in tumor tissue resistance and the slope of the resistance curve were both significant in predicting LFR (p = 0.02 and p = 0.01, respectively). The median local disease-free survival was 5.5 months in patients who had recurrence compared with 12.6 months in patients who did not recur (p = 0.03). Neither mean change in tumor tissue resistance nor the slope of the resistance curve significantly predicted overall DFS. CONCLUSIONS Mean change in tumor tissue resistance and the slope of the resistance curve could be used intraoperatively to assess successful tumor ablation during IRE. Larger sample size and longer follow-up are needed to determine if these parameters can be used to predict DFS.

Evaluation of thermal injury to liver, pancreas and kidney during irreversible electroporation in an in vivo experimental model.

Irreversible electroporation (IRE) is a new technique for tumour cell ablation that is reported to involve non‐thermal‐based energy using high voltage at short microsecond pulse lengths. In vivo assessment of the thermal energy generated during IRE has not been performed. Thermal injury can be predicted using a critical temperature model. The aim of this study was to assess the potential for thermal injury during IRE in an in vivo porcine model.

Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model.

Irreversible electroporation (IRE) is a promising cell membrane ablative modality for pancreatic cancer. There have been recent concerns regarding local recurrence and the potential use of IRE as a debulking (partial ablation) modality. We hypothesize that incomplete ablation leads to early recurrence and a more aggressive biology. We created the first ever heterotopic murine model by inoculating BALB/c nude mice in the hindlimb with a subcutaneous injection of Panc-1 cells, an immortalized human pancreatic adenocarcinoma cell line. Tumors were allowed to grow from 0.75 to 1.5 cm and then treated with the goal of complete ablation or partial ablation using standard IRE settings. Animals were recovered and survived for 2 days (n = 6), 7 (n = 6), 14 (n = 6), 21 (n = 6), 30 (n = 8), and 60 (n = 8) days. All 40 animals/tumors underwent successful IRE under general anesthesia with muscle paralysis. The mean tumor volume of the animals undergoing ablation was 1,447.6 mm3 ± 884). Histologically, in the 14-, 21-, 30-, and 60-day survival groups the entire tumor was nonviable, with a persistent tumor nodule completely replaced fibrosis. In the group treated with partial ablation, incomplete electroporation/recurrences (N = 10 animals) were seen, of which 66% had confluent tumors and this was a significant predictor of recurrence (P < 0.001). Recurrent tumors were also significantly larger (mean 4,578 mm3 ± SD 877 versus completed electroporated tumors 925.8 ± 277, P < 0.001). Recurrent tumors had a steeper growth curve (slope = 0.73) compared with primary tumors (0.60, P = 0.02). Recurrent tumors also had a significantly higher percentage of EpCAM expression, suggestive of stem cell activation. Tumors that recur after incomplete electroporation demonstrate a biologically aggressive tumor that could be more resistant to standard of care chemotherapy. Clinical correlation of this data is limited, but should be considered when IRE of pancreatic cancer is being considered.

Caudate lobe resections: a single-center experience and evaluation of factors predictive of outcomes

BackgroundDespite the increasing frequency of liver resection for multiple types of disease, caudate lobe resection remains a rare surgical event. The goal of this study is to review our experience and evaluate possible predictors of adverse outcomes in patients undergoing caudate lobectomy.MethodsWe reviewed a 1,900-patient prospective hepato-pancreatico-biliary database from January 2000 to December 2011, identifying 36 hepatectomy patients undergoing caudate lobe resection. Clinicopathologic characteristic and outcome data were compared using chi-square, T-test, ANOVA, Kaplan-Meier, and Cox regression analysis. Primary endpoints were the incidence and severity of complications, and secondary endpoints were blood loss, hospital stay, and transfusion requirements. Patients were also divided in two groups with group A being patients operated on before December 2007 and group B after 2007. We compared the demographics, risk factors, complication rates, and operative details between the two groups.ResultsThirty-six patients underwent caudate lobe resection for cholangiocarcinoma (47.2%), metastatic colorectal cancer (36.1%), hepatocellular carcinoma (8.3%), or benign disease (8.3%). Nine patients (29%) had additional liver resection. Median overall survival (OS) was 21 months. Complications occurred in 52.7% (19/36) of patients with a median grade of 2. Tobacco abuse was associated with an increased risk of operative complications (73.3% vs. 38.9%, p = 0.03). Prior history of cardiac disease was associated with a higher complication rate (87% vs. 42%, p = 0.03). Neoadjuvant chemotherapy, biliary procedures, hepatitis, and prior major abdominal surgery were not predictive of complications. Major complication was also predicted by the volume of RBC transfusion (2.7 vs. 4.1 units, p = 0.003). In our subgroup analysis of the patients undergoing surgery before and after 2007, the two groups were well matched based on age, comorbidities, and risk factors. The complication rates and rates of high-grade complications were similar, but blood loss (600 ml vs. 400 ml, p = 0.03), inflow occlusion time (Pringle time 12.6 vs. 6, p = 0.00), and hospital stay (9.5 vs. 7 days, p = 0.01) were significantly lower in group B.ConclusionsWith appropriate patient selection, caudate lobe resection is an effective component of surgery for hepatic disease. Tobacco use and prior cardiac history increase the risk of complications.

Gastric-Esophageal Stenting for Malignant Dysphagia: Results of Prospective Clinical Trial Evaluation of Long-Term Gastroesophageal Reflux and Quality of Life-Related Symptoms

BACKGROUND Stenting across the gastroesophageal (GE) junction for adenocarcinoma has historically been contraindicated secondary to the concerns for severe GE reflux (GER) symptoms. The aim of this study was to assess reflux symptoms and quality of life (QOL) effects in patients undergoing esophageal stenting across the GE junction. STUDY DESIGN We performed a prospective single arm QOL clinical trial evaluating patients with stage 2/3 GE junction adenocarcinoma, undergoing neoadjuvant therapy (from baseline to 10 weeks post-stenting) after stenting across the GE junction, for GER symptoms and QOL-GER assessments (EORTC-QLQ-O25 and Functional Assessment of Cancer Therapy-Esophageal [FACT-E]). RESULTS Forty consecutive patients were enrolled in this clinical trial. The median age was 62 years (range 47 to 83 years); 84% were male and 19% were female patients. Median dysphagia score of 3 (only liquids tolerated) pre-stent was significantly improved to a score of 0 (ability to eat all foods) post-stent (p = 0.01). There was a significantly improved and sustained swallowing QOL from 2 weeks up to 10 weeks post-stent. The GER-QOL scores were similar 2 weeks post-stent, but were significantly improved throughout the rest of the study. Proton pump inhibitors were being used in 58% of patients pre-stent and in 85% of patients at 2- to 10-week follow-up. Planned chemotherapy and/or chemo-radiation therapy was completed in 95% of all patients. Stent migration (radiologic and/or complete) was seen in 63% of patients at some time during their therapy and corresponded to pathologic response in 85% of those patients. CONCLUSIONS Esophageal stenting across the GE junction remains the optimal therapy for dysphagia relief in esophageal malignancies and does not adversely affect a patients GER-QOL. Esophageal stenting across the GE junction is not contraindicated and should be the initial therapy in patient management.

Incidence and risk factors for deep venous thrombosis and pulmonary embolus after liver transplantation

BACKGROUND Omitting chemical venous thromboembolism prophylaxis in liver transplant recipients may lead to an increase incidence of deep venous thrombosis (DVT) and/or pulmonary embolus (PE). METHODS A retrospective comparison of liver transplant recipients who developed postoperative DVT/PE to an age-matched population. RESULTS Forty-three of eight hundred sixty-seven patients developed a DVT/PE. Study group patients received higher amounts of cryoprecipitate and fresh frozen plasma. Study group international normalized ratio (INR) was significantly higher, as was the incidence of postoperative complications. High-grade complication rates (bleeding, respiratory failure, and renal insufficiency) were increased in the study group at 16% vs 0%. CONCLUSIONS The present study demonstrates that the rate of DVT/PE after liver transplantation is similar to the rate after other major operations. Patients were more likely to develop DVT/PE if they received increased amounts of intraoperative cryoprecipitate/fresh frozen plasma (FFP) or had an elevated postoperative INR. Furthermore, patients with a complicated postoperative course have the highest risk of venous thromboembolism.

Impact of surgical margin clearance for resection of secondary hepatic malignancies.

Over the past several decades, there has been increasing discussion regarding the optimal management of secondary liver malignancies. Traditionally, resection has only been recommended if it could be accomplished with negative microscopic margins of at least 10 mm. However, many investigators have pushed this limit to offer resection to patients with narrower margins. We review the data regarding the impact of margin clearance on outcomes for patients undergoing hepatic metastasectomy. J. Surg. Oncol. 2016;113:289–295.

Low-energy DC current ablation in a mouse tumor model.

Irreversible electroporation has recently been applied to tissue and tumor ablation. This animal model was developed to evaluate optimal parameters for subcutaneous tumor ablation. The immortalized Panc1 tumor cell line was used for generating tumors via subcutaneous injection in mice. Under general anesthesia with complete muscle relaxation, electroporation was performed with the NanoKnife device. Post-procedure tumors were recovered and studied at specified time intervals to assess the efficacy.

Restrictive blood transfusion protocol in malignant upper gastrointestinal and pancreatic resections patients reduces blood transfusions with no increase in patient morbidity.

BACKGROUND The purpose of this study was to determine the impact of a restrictive blood transfusion protocol on the number of transfusions performed and the related effect on patient morbidity. METHODS A cohort study was performed using our prospective database with information from January 1, 2000, to June 1, 2013. The restrictive blood transfusion protocol was implemented in September 2011, so this date served as the separation point for the date of operation criteria. RESULTS For the study, 415 patients undergoing operation for an abdominal malignancy were reviewed. After the restrictive blood transfusion protocol, the percentage of patients who received blood dropped from 35.6% to 28.3%. The percentage of patients who experienced perioperative complication was significantly higher in transfused patients compared with those who did not receive blood (P = .0001). There was no statistical significance observed between the 5 groups for the length of stay at the hospital after their procedure. CONCLUSIONS The restrictive blood transfusion protocol resulted in a reduction of the percentage of patients transfused, and there was no evidence to suggest that it negatively affected the outcomes of patients in this group.