Susan Ellis

Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures

Irreversible electroporation (IRE) has shown promise for ablation of lesions in proximity to vital structures in the preclinical setting. This study aims to evaluate the safety and efficacy of IRE for hepatic tumors in the clinical setting.

Irreversible Electroporation Therapy in the Management of Locally Advanced Pancreatic Adenocarcinoma

BACKGROUND Locally advanced pancreatic cancer patients have limited options for disease control. Local ablation technologies based on thermal damage have been used but are associated with major complications in this region of the pancreas. Irreversible electroporation (IRE) is a nonthermal ablation technology that we have shown is safe near vital vascular and ductal structures. The aim of this study was to evaluate the safety and efficacy of IRE as a therapy in the treatment of locally advanced pancreatic cancer. STUDY DESIGN We performed a prospective multi-institutional pilot evaluation of patients undergoing IRE for locally advanced pancreatic cancer from December 2009 to March 2011. These patients were evaluated for 90-day morbidity, mortality, and local disease control. RESULTS Twenty-seven patients (13 women and 14 men) underwent IRE, with median age of 61 years (range 45 to 80 years). Eight patients underwent margin accentuation with IRE in combination with left-sided resection (n = 4) or pancreatic head resection (n = 4). Nineteen patients had in situ IRE. All patients underwent successful IRE, with intraoperative imaging confirming effective delivery of therapy. All 27 patients demonstrated nonclinically relevant elevation of their amylase and lipase, which peaked at 48 hours and returned to normal at 72 hour postprocedure. There has been one 90-day mortality. No patient has shown evidence of clinical pancreatitis or fistula formation. After all patients have completed 90-day follow-up, there has been 100% ablation success. CONCLUSIONS IRE ablation of locally advanced pancreatic cancer tumors is a safe and feasible primary local treatment in unresectable, locally advanced disease. Confirming these early results must occur in a planned phase II investigational device exemption (IDE) study to be initiated in 2012.

Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis

BACKGROUND The goal of this study was to examine the safety and efficacy of selective internal radioembolization (SIR) for hepatocellular carcinoma (HCC) with portal vein or caval thrombosis (VT), or both. Recent reports have demonstrated that SIR is safe for patients with HCC, but the impact on efficacy of venous thrombosis is unknown. STUDY DESIGN Prospective single-arm study of the use of Therasphere in patients with unresectable HCC enrolled from January 2004 to June 2007. Patients were categorized into three groups based on VT status and therapy. RESULTS Fifty-two patients were enrolled: 20 patients without VT who received SIR, 15 patients with VT who were treated, and 17 patients (10 with VT) who were not treated because of preprocedure screening failure. Fifty-eight treatments were administered, with a median of two treatments per patient (range of one to three treatments). Childs score was different between groups. Of the VT patients treated, 67% had portal VT, 7% had cava VT, and 26% had both. There were no treatment-related deaths. There was no difference in complications among groups (p = 0.34). Treated patients without thrombosis had a median overall survival of 13.9 months versus 2.7 months for those treated with thrombosis and 5.2 months for the untreated group given best supportive care only (p = 0.01). CONCLUSIONS SIR is safe in patients with HCC. Although SIR can be delivered with minimal morbidity, there might be no benefit for patients with VT. Continued emphasis on multimodality therapy in this population is needed to improve survival.

A Prospective Phase II Evaluation of Esophageal Stenting for Neoadjuvant Therapy for Esophageal Cancer: Optimal Performance and Surgical Safety

BACKGROUND Many surgeons are reluctant to use esophageal stents during neoadjuvant therapy for esophageal cancer because of concerns about nutritional status, stent-related complications, or added difficulties during esophagogastrectomy. We hypothesized that esophageal stenting during neoadjuvant therapy allows for optimal nutritional intake without adversely affecting perioperative outcomes. STUDY DESIGN This study is a prospective, dual-institution, single-arm, phase II evaluation of esophageal cancer patients undergoing neoadjuvant therapy before resection. All patients had a self-expanding polymer stent placed before neoadjuvant therapy. We monitored dysphagia symptoms, nutritional status, stent-related complications, and perioperative complications during the course of therapy and 90 days postoperatively. RESULTS We enrolled 32 patients with dysphagia and weight loss who were eligible for neoadjuvant therapy. After stent placement, 2 patients had stent migrations requiring replacement. No erosive complications were observed. During the course of neoadjuvant therapy, we noted improvement in dysphagia, mild weight loss, and maintenance of performance status. At a median of 50 days (range 18 to 92 days) after completion of neoadjuvant therapy, 20 patients underwent margin-negative esophagogastrectomy (16 Ivor Lewis, 4 minimally invasive) without problems with stent removal or difficulty in surgical dissection. Twelve patients did not undergo resection due to development of metastases (n = 8) or rapid decline in functional status (n = 4). Major perioperative complications included pulmonary embolism (n = 2), chyle leak (n = 1), and bronchial injury (n = 1). No surgical complications were attributed to stent placement. CONCLUSIONS Use of esophageal stents during neoadjuvant therapy is safe and results in resolution of dysphagia, mild weight loss, and maintenance of performance status without an effect on intraoperative dissection, perioperative complications, or delay in resection after neoadjuvant therapy.

Safety of Hepatic Resection in Metastatic Disease to the Liver After Yttrium-90 Therapy

BACKGROUND Unresectable hepatic metastases from aerodigestive cancers are common and in most cases herald a poor prognosis. A small percentage of patients maybe amenable to surgical resection or ablation once the biology of the disease and the burden of hepatic disease are better understood. The use of hepatic arterial resin microspheres containing the β emitter, yttrium-90, has been reported in the treatment of unresectable hepatic metastases. The goal of this review was to evaluate the use of yttrium-90 hepatic arterial therapy in the management of hepatic metastases and surgical downstaging. METHODS We reviewed our prospective hepatic arterial therapy registry and found 44 patients who had received Sir Sphere treatment for unresectable hepatic malignancies from 11/06 to 7/08. Response was assessed by using CT-imaging and characterized using modified response evaluation criteria in solid tumors (RECIST). All patients were managed in a multidisciplinary tertiary referral center specializing in hepatic malignancies. RESULTS A total of 44 patients, 34 men and 10 women, with a median age of 60 y (range 44-8), received 67 treatments. The disease types treated were one adenosquamous tongue, one adrenal, nine carcinoid, three cholangiocarcinoma, four esophageal, one gastric, one gastrinoma, one GIST, four HCC, 15 colorectal, one melanoma, one non-small-cell lung, one occular, and one sarcoma. Four patients treated proceeded to resection because of downstaging of disease or no evidence of extrahepatic progression. The median age in these patients was 61 y (range 49-62). All of the patients had less than 25% tumor burden in the liver. Surgical therapy consisted of two patients undergoing right hepatic lobectomy, one patient who also underwent two wedge resections of segment 3, and one patient who had a left lateral hepatectomy with right lobe microwave ablation. The median length of postoperative stay was 7 d. There was no evidence of liver dysfunction following resection in any of the patients. None of the patients show evidence of recurrence in the liver following resection. One patient has had progression of disease in the lungs following resection, histologically confirmed as metastatic rectal carcinoma. All of the patients are currently alive with a median survival of 2 y. CONCLUSION Hepatic directed yttrium-90 is a minimally invasive, highly effective therapy that can be utilized to downstage the hepatic burden and/or assess the biology of the disease to allow for appropriate treatment. The use of yttrium-90 microspheres for radio-embolization of metastases in the liver can successfully downstage the lesions to allow for surgical resection in patients with amenable predictors, and can provide a significantly better prognosis in these patients. This form of therapy for the purposes of downstaging tumors for resection merits more extensive study in order to provide the best possible outcomes for patients with metastatic liver disease.

Assessment of symptom experience in patients undergoing hepatic resection or ablation

Quality of life (QOL) currently is considered both clinically meaningful and biologically important for patient outcome and is considered as important as disease‐free and overall survival. Thus, the objective of the current study was to evaluate the QOL symptoms of patients who underwent major hepatic resection, minor hepatic resection, and ablation for primary or metastatic cancer to the liver.

A Novel External Esophageal Perfusion Model for Reflux Esophageal Injury

The current animal models of esophagitis and Barrett’s esophagus consist of surgeries that divert the gastroduodenal contents to the esophagus. The limitations of these models are the inability to control the amount and concentration of the refluxate and the causing of significant postoperative stress and morbidity. Eighteen adult rats were cannulated at the upper esophagus and connected to a subcutaneous osmotic micropump to perfuse the esophageal lumen with bile and acid. Animals were sacrificed after 7 days of perfusion. Histological changes were determined. Cell proliferation, apoptosis, lipid peroxidation, and glutathione were measured. Histopathological changes in the bile- or acid-perfused esophagus were consistent with the findings associated with reflux esophagitis. Enhanced proliferation and apoptosis were seen, along with increased oxidative stress. The external esophageal perfusion model enabled precise control of the injurious agent. It induced the histologic and cellular injurreflux esophagitis after 7 days.

Evaluation of Quality of Life Following Placement of Self-Expanding Plastic Stents as a Bridge to Surgery in Patients Receiving Neoadjuvant Therapy for Esophageal Cancer

PURPOSE To determine whether self-expanding plastic stent (SEPS) placement significantly improves quality of life and maintains optimal nutrition while allowing full-dose neoadjuvant therapy (NAT) in patients with esophageal cancer. PATIENTS AND METHODS A prospective, dual-institution, single-arm, phase II (http://ClinicalTrials.gov: NCT00727376) evaluation of esophageal cancer patients undergoing NAT prior to resection. All patients had a self-expanding polymer stent placed prior to NAT. The European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25, Functional Assessment of Cancer Therapy-Anorexia, and Functional Assessment of Cancer Therapy-General surveys were administered prior to stenting, within 1 week post-stent placement, and at the completion of neoadjuvant therapy. RESULTS Fifty-two patients were enrolled; 3 (5.8%) had stent migrations requiring replacement. There were no instances of esophageal erosion or perforation. All patients received some form of neoadjuvant therapy. Thirty-six (69%) received chemoradiation; 34 (93%) of these patients received the planned dose of chemotherapy, and 27 (75%) received the full planned dose of radiotherapy. There were 16 (31%) patients receiving chemotherapy alone; 12 (74%) of patients in the chemotherapy-alone group completed the planned dose of therapy. CONCLUSION Placement of SEPS appears to provide significant improvement in quality of life related to dysphagia and eating restriction in patients with esophageal cancer undergoing neoadjuvant therapy. Consideration of SEPS instead of percutaneous feeding tube should be initiated as a first line in dysphagia palliation and NAT nutritional support.

Impact of Post-Operative Complications on Quality of Life After Pancreatectomy

CONTEXT Pancreatectomies for malignant and benign diseases are increasingly being performed worldwide. Recent studies, that have evaluated quality of life in pancreatectomy, have reported conflicting outcomes. OBJECTIVE This study was undertaken to analyze the quality of life changes reported by patients with pancreatic cancer undergoing pancreatectomy. DESIGN Post-hoc analysis was performed of a clinical trial examining the safety of intraoperative autotransfusion during oncologic resections. MAIN OUTCOME MEASURES Perioperative (90-day) complications were graded prospectively using a validated 5-point scale. Quality of life parameters were recorded prospectively by a single trained interviewer preoperatively, at the first post-operative outpatient visit, and at 6 weeks, 3 months, and 6 months follow-up using the EORTC QLQ-C30 and FACT-An instruments. RESULTS Pancreatectomy for adenocarcinoma was performed in 34 patients with a median follow-up of 2 years (range: 1-1.5 years). Major (grade≥3) complications occurred in 12 (35.3%) of patients. Early (<6 month) recurrence was noted in 2 patients (5.9%). Increased severity of fatigue, pain, dyspnea, and loss of appetite over baseline were noted at initial follow-up (P<0.05); however, symptom scores normalized at 6-week follow-up, and remained stable at 6 months. No significant difference was noted in quality of life metrics between patients with or without major complications (P>0.11). A significant (P=0.023) decline in cognitive function vs. baseline was noted at 6-month follow-up after pancreatectomy. Using a repeated-measures generalized linear model, neither age, nor complication occurrence, nor adjuvant therapy, nor early recurrence accounted for this cognitive decline (P>0.10). CONCLUSION Quality of life metrics tend to normalize to preoperative levels after pancreatectomy at 6 weeks post-operatively. The occurrence of major complications does not predict a decreased quality of life. The decrease in self-reported cognitive function at six months in this cohort merits further study.