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.

Student-Authored Autopsy Reports of Anatomical Donors: Their First Patients.

The preparation of student-authored autopsy reports of anatomical donors was added to the Gross Anatomy course to integrate the basic and clinical sciences and determine whether students considered this early clinical exposure to be a valuable experience. All donors were scanned using computerized tomography (CT) and student groups received the scan of their donor and a report written by a radiologist. As students dissected, they took photographs and biopsies of pathological findings that were processed for microscopic evaluation. Following consultation with pathologists and radiologists, each group prepared an autopsy report that proposed a cause of death supported with macroscopic, microscopic, and CT images. Cardiovascular events and cancer were the most common. Autopsy reports were evaluated by the faculty and each student group received feedback with respect to content, accuracy, and completeness and whether faculty agreed with students' proposed cause of death. A majority of students answering an anonymous survey indicated that this exercise was valuable or somewhat valuable, but did not agree that preparation of the autopsy report resulted in their being more engaged during the course. Students agreed or somewhat agreed that the exercise should be repeated next year, that they gained insight into the clinical manifestations of disease, that they were able to interpret the CT scan themselves, that meeting with a pathologist was interesting, and that the time required to prepare the report was adequate. Since autopsy reports prepared by students are feasible and students found it to be a valuable experience, we suggest that medical schools add this to Gross Anatomy courses to introduce clinical material and increase clinical relevance.

Practical Considerations Relating to Routine Clinical Biomarker Testing for Non-small Cell Lung Cancer: Focus on Testing for RET Fusions.

For patients with advanced non-small cell lung cancer, genomic profiling of tumors to identify potentially targetable alterations and thereby inform treatment selection is now part of standard care. While molecular analyses are primarily focused on actionable biomarkers associated with regulatory agency-approved therapies, there are a number of emerging biomarkers linked to investigational agents in advanced stages of clinical development will become approved agents. A particularly timely example is the reported data and US Food and Drug Administration approval of highly specific small molecule inhibitors of the proto-oncogene tyrosine-protein kinase receptor RET indicate that testing for tumor RET gene fusions in patients with NSCLC has become clinically important. As the number of biomarkers to be tested in NSCLC grows, it becomes increasingly important to optimize and prioritize the use of biopsy tissue, in order to both continue to allow accurate histopathological diagnosis and also to support concurrent genomic profiling to identify perhaps relatively uncommon genetic events. In order to provide practical expert consensus guidance to optimize processes facilitating genomic testing in NSCLC and to overcome barriers to access and implementation, a multidisciplinary advisory board was held in New York, on January 30, 2019. The panel comprised physicians involved in sample procurement (interventional radiologists and a thoracic surgeon), surgical pathologists specializing in the lung, molecular pathologists, and thoracic oncologists. Particular consideration was given to the key barriers faced by these experts in establishing institutional genomic screening programs for NSCLC. Potential solutions have been devised in the form of consensus opinions that might be used to help resolve such issues.

Single-Institution Experience with Irreversible Electroporation for T4 Pancreatic Cancer: First 50 Patients.

BACKGROUND: Irreversible electroporation (IRE) for treatment of locally advanced pancreatic tumors is garnering increasing attention. This study was conducted to determine perioperative morbidity and mortality for locally advanced pancreatic cancer. METHODS: Prospective data of 50 consecutive patients receiving IRE for T4 lesions at a single tertiary center were analyzed. The primary end point was Clavien-Dindo complications at 90 days, and the secondary outcomes were survival and recurrence. RESULTS: A total of 50 patients underwent 53 IRE procedures for primary treatment (n = 29) or margin extension (n = 24), and 47 patients had adenocarcinoma. Six patients died within 90 days after the procedure (5 in the primary control group). Mortality occurred a median of 26 days (range, 8-42 days) after the procedure. Five patients in both the margin-extension and primary control groups experienced grade 3 or 4 morbidity (p = 0.739). The incidences of grades 3 to 5 complications did not differ significantly based on the adjustable parameters of IRE, tumor size, or primary treatment versus margin extension. After a median follow-up period of 8.69 months [interquartile range (IQR), 0.26-16.26 months], the median overall survival period for the primary control group was 7.71 months [95 % confidence interval (CI), 6.03-12.0 months) and was not reached in the margin-extension group (p = 0.01, log-rank). CONCLUSIONS: At the authors' center, the mortality rate after IRE was higher than reported in other series, with the majority occurring in the primary control group. Major morbidity trended around upper gastrointestinal bleeding, visceral ulcerations/perforations, and portal vein thromboses. This favors further investigation of the safety and efficacy of IRE.

An evaluation of the sensitivity of MRI at detecting hepatocellular carcinoma in cirrhotic patients utilizing an explant reference standard.

OBJECTIVE: To evaluate the sensitivity of magnetic resonance imaging (MRI) at detecting hepatocellular carcinoma (HCC). MATERIALS AND METHODS: MRIs performed within 120 days of transplant, and pathology, were reviewed. RESULTS: Of the 87 patients included in the final analysis, 58 had HCC at explant (106 total HCCs). The per-patient and per-lesion sensitivity was 74.1% (43/58) and 81.1% (86/106), respectively. The sensitivity based on size <1cm, 1-2 cm, and >2 cm was 80.0% (28/35), 77.2% (44/57), and 100% (14/14). CONCLUSION: MRI accurately detects HCC, including HCCs <2 cm. In our study population, the imaging disease staging was concordant with pathological staging in 80% of patients.

Bland embolization versus chemoembolization of hepatocellular carcinoma before transplantation.

There is conflicting literature regarding the superiority of transarterial chemoembolization (TACE) versus bland transarterial embolization (TAE), and this has not been well studied before transplantation. Twenty-five TAE patients were matched in a 1:2 ratio with TACE patients by the initial radiographic tumor size and number in a retrospective, case-controlled study. The patients were otherwise treated according to the same protocols. The method of embolization was chosen on the basis of interventionalist practices at 2 sites within the program. Kaplan-Meier survival analyses at 1 and 3 years were the primary endpoints. There were no significant demographic differences between the groups. The mean adjusted Model for End-Stage Liver Disease scores at transplantation and waiting times were not significantly different between the TAE and TACE patients (MELD scores: 26 ± 3 versus 24 ± 3 points, P = 0.12; waiting times: 13 ± 8 versus 11 ± 10 months, P = 0.43). TAE patients (16%) were less likely than TACE patients (40%) to require 2 procedures (P = 0.04). Explant tumors were completely necrotic for 36% of the TAE patients and for 26% of the TACE patients. The 3-year overall survival rates were 78% for the TAE patients and 74% for the TACE patients (P = 0.66), and the 3-year recurrence-free survival rates were 72% for the TAE patients and 68% for the TACE patients (P = 0.67). On an intention-to-treat basis, there was no significant risk of wait-list dropout associated with TAE or TACE (P = 0.83). In conclusion, there were no significant differences in wait-list dropout or in overall or recurrence-free survival between HCC patients undergoing TAE and HCC patients undergoing TACE before transplantation.

Electromagnetic navigation with multimodality image fusion for image-guided percutaneous interventions.

Percutaneous image-guided interventions are performed for a variety of clinical indications: to obtain tissue biopsies, to alleviate pain, and to treat diseases including a variety of malignancies. The efficacy of all of the above is directly related to accurate positioning of the procedural device using imaging guidance. The ability to achieve accurate positioning can be limited by a variety of technical factors including small lesion size, a lesion that is best seen on an imaging modality that is impractical for guiding intervention, and a lesion that is difficult to access or in a tenuous location. Electromagnetic navigation with image fusion has the ability to improve the speed and accuracy of percutaneous image-guided interventions by providing real-time feedback and allowing image overlay of diagnostic-imaging modalities with the guiding modality. The article discusses the technical aspects of electromagnetic navigation including potential clinical applications, procedures that may be facilitated by navigation, and inherent limitations of the technology.

Interventional radiology in the multidisciplinary management of liver lesions: pre- and postoperative roles.

The management algorithm for patents with liver lesions, most often hepatocellular carcinoma (HCC) or colorectal cancer metastasis, are complex, ever-changing, and involve multiple treatment modalities including chemotherapy, external-beam radiation, surgery, and locoregional therapies (LRTs). This complexity necessitates a multidisciplinary approach including hepatologists, oncologists, hepatobiliary surgeons, radiation oncologists, and interventional radiologists to coordinate and deliver the complex care that these patients need in a timely manner. The interventional radiologist and hepatobiliary surgeon work closely together in both the pre- and postoperative setting. Preoperative roles include delivering LRTs to patients with HCC and interventions aimed at hepatic optimization prior to resection or transplantation. LRT in this setting is performed either to bridge the patient to transplant or to downstage the initially nontransplant candidate so appropriate transplant criteria are met. Postoperative roles include the management of biliary and vascular complications that may occur after resection or transplantation.

Treatment of hepatocellular carcinoma combining sorafenib and transarterial locoregional therapy: state of the science.

The potential for increased efficacy with combined transarterial chemoembolization and sorafenib is a topic of increased interest to specialists who care for patients with unresectable hepatocellular carcinoma. There is strong scientific rationale for combination therapy: transarterial chemoembolization produces ischemia and stimulates hypoxia-inducible factor-1α, resulting in a local and systemic upregulation of vascular endothelial growth factor (VEGF), which can increase tumor angiogenesis. This upregulation can theoretically be counteracted with the multikinase inhibitor sorafenib, which is thought to act directly on platelet-derived growth factor, Raf kinase, and VEGF receptors. The potential of this approach has not yet been fully realized in clinical trials, and many unanswered questions remain. This review article discusses the state of the science of arterial locoregional therapies and sorafenib.

Emergent embolization of arterial bleeding after vacuum-assisted breast biopsy.

Vacuum-assisted core breast biopsy has become important in evaluating patients with suspicious breast lesions. It has proven to be a relatively safe procedure that in rare cases can result in vascular complications. These are the first reported cases of transcatheter embolization of uncontrolled breast hemorrhage after vacuum-assisted breast biopsy. With increased use of biopsy and larger-gauge devices, breast imaging groups may consider embolotherapy as a safe alternative for treatment of hemorrhage in a select group of patients.

Gastroduodenal ulceration associated with radioembolization for the treatment of hepatic tumors: an institutional experience and review of the literature.

BACKGROUND: Microsphere radioembolization is a method of delivering radiation therapy directly to tumors, thereby minimizing toxicity to adjacent structures. Despite the relatively high precision of this modality, numerous adverse effects have been recognized. One particularly untoward complication is the development of severe gastroduodenal ulceration. METHODS: In order to further characterize gastroduodenal ulceration associated with radioembolization, our institutional experience as well as the reported literature were reviewed. RESULTS: The current evidence suggests that radioembolization-associated gastroduodenal ulceration results from inadvertent delivery of microspheres to the microvasculature of the gastrointestinal tract, leading to direct radiation toxicity. The reported incidence of this entity ranges between 2.9% and 4.8%. Most patients with this complication present with abdominal pain, often associated with nausea, vomiting, and anorexia. Symptoms can arise from hours to months after radioembolization treatment; diagnosis is made by endoscopic biopsy and histopathologic evaluation of the ulcer specimen. Radiation-induced ulcers have proven to be extremely difficult to treat. Current therapy based on acid suppression has had limited success, and the evidence for the addition of antioxidants and anti-inflammatory agents is still sparse. CONCLUSIONS: The increasing utilization of radioembolization will lead to adverse events including gastroduodenal ulceration. This entity must be considered in any patient treated with radioactive microspheres presenting with symptoms of dyspepsia. Accurate diagnosis and aggressive treatment are necessary to improve patient outcomes.

Intra-arterial methylprednisolone infusion in treatment-resistant graft-versus-host disease.

Acute graft-versus-host disease (GVHD) is a potentially fatal complication following allogeneic hematopoietic stem cell transplant. Standard primary therapy for acute GVHD includes systemic steroids, often in combination with other agents. Unfortunately, primary treatment failure is common and carries a high mortality. There is no generally accepted secondary therapy for acute GVHD. Although few data on localized therapy for GVHD have been published, intra-arterial injection of high-dose corticosteroids may be a viable option. We treated 11 patients with steroid-resistant GVHD using a single administration of intra-arterial high-dose methylprednisolone. Three patients (27%) died periprocedurally. Four patients (36%) had a partial response to intra-arterial treatment and were discharged on total parenteral nutrition and oral medication. Four patients (36%) had a complete response and were discharged on oral diet and oral medication. No immediate treatment or procedure-related complications were noted. Twenty-seven percent of patients survived long-term. Our preliminary results suggest that regional intra-arterial treatment of steroid-resistant GVHD is a safe and potentially viable secondary therapy in primary treatment-resistant GVHD.

Transarterial chemoembolization for primary hepatocellular carcinoma in patients at high risk.

PURPOSE: Transarterial chemoembolization (TACE) has become a standard treatment option for patients with unresectable hepatocellular carcinoma (HCC). This retrospective study evaluated the safety and efficacy of TACE in patients at high risk with increased serum bilirubin level, low serum albumin level, poor hepatic reserve, or compromised hepatopetal flow in the portal vein (PV). MATERIALS AND METHODS: A total of 52 patients underwent 65 high-risk procedures. Thirty patients treated with 38 procedures (57.7% of patients and 58.5% of procedures) had serum bilirubin levels of 2-3 mg/dL (ie, moderate elevation) and 22 patients treated with 27 procedures (42.3% and 41.5%) had a serum bilirubin level of at least 3 mg/dL (ie, considerable elevation). Forty patients (76.9%) had serum albumin levels less than 3.5 mg/dL. Thirteen recipients of 15 procedures (25% and 20%) had portal diversion or obstruction. Twenty-four patients (46.2%) had a Child-Pugh (CP) score of 8 or less and 28 patients (53.8%) had a CP score of at least 9 at the time of TACE. Thirty patients (57.7%) had focal tumors and 22 patients (42.3%) had multifocal or infiltrative disease. Superselective chemoembolization could be performed in 37 procedures (56.9%); lobar chemoembolization was performed in the remaining 28 (43.1%). RESULTS: The 30-day mortality rate was 7.7% and the procedure-related morbidity rate was 10.8%. Patients with multifocal disease and lobar embolization had significantly higher mortality rates (P=.03). Individual factors such as serum bilirubin, serum albumin, and PV flow did not affect outcomes significantly. The 1- and 2-year survival rates in patients with focal disease were 67.9% and 37.7%, respectively, compared with 19.6% and 0% in patients with multifocal disease (P<.0001). CONCLUSIONS: TACE in patients considered at high risk does not necessarily incur a higher incidence of morbidity or mortality. Patient selection should be based on extent of disease, and these tumors should be treated selectively at a segmental level if possible.

Treatment of a biliary-venous fistula following percutaneous biopsy in a pediatric living related liver transplant patient.

Liver biopsy is a common study performed after hepatic transplantation. Most centers routinely perform a biopsy 1 week after surgery to evaluate for the possibility of acute rejection. Subsequent biopsies are based on clinical symptoms and routine hepatic function laboratory testing. We report the clinical presentation and treatment of a biliary-venous fistula resulting in sepsis and bilhemia (elevated serum bilirubin levels caused by a biliary-venous fistula) in a 2(1/2)-year-old patient 4 months after partial left lateral segment living related liver transplantation. This case is unusual in that the fistula is the reversal of the more common venous-biliary fistula. The fistula developed after a percutaneous liver biopsy was performed.

Preoperative angiography with embolization and radiofrequency ablation as novel adjuncts to safe surgical resection of a large, vascular sacrococcygeal teratoma.

Sacrococcygeal teratomas (SCTs) can present a challenging problem and can be associated with significant perinatal morbidity and mortality. A female child was born at 36 weeks' gestation with a large, vascular Type 1 SCT originally identified by prenatal ultrasound. A CT scan showed two large feeding vessels arising from both internal iliac arteries that were successfully embolized during angiography. A radiofrequency probe was then used to ablate a zone between normal tissue and the tumor. The SCT was subsequently surgically excised with minimal blood loss. This case is presented to illustrate two useful and previously unreported postnatal adjuncts to the surgical treatment of massive, hypervascular sacrococcygeal tumors.

Uterine artery embolization: sonographic imaging findings.

OBJECTIVE: To examine the sonographic and angiographic imaging findings before and after uterine fibroid embolization for symptomatic leiomyoma. METHODS: This prospective study involved 14 premenopausal women who underwent uterine fibroid embolization for symptomatic leiomyoma. Preprocedure sonography with color Doppler imaging was performed. Bilateral uterine artery embolization was successfully performed with the use of polyvinyl alcohol. Follow-up sonographic examinations were performed between 1 and 3 months after the procedure. The correlation between the sonographic appearance before and after embolization and the degree of decrease in uterine size was evaluated by using the Jonckheere-Terpstra 2-sided P test. RESULTS: Preprocedure sonographic imaging showed a varied appearance to the fibroids. Color Doppler imaging primarily showed the fibroids to be vascular with marked peripheral blood flow. Postprocedure sonographic imaging showed decreased uterine size and echogenicity. Color Doppler imaging showed a marked decrease in the blood flow to the leiomyoma. There was no statistical significance in the relationship between echogenicity and vascularity shown before the procedure and the percent decrease in the size of the uterus. CONCLUSIONS: Although sonography is an efficient method for identifying leiomyomata and determining the reduction in size after uterine artery embolization, we were unable to identify any predictive characteristics of success for aiding the preprocedural assessment.

Radiofrequency ablation for hemobilia secondary to hepatocellular carcinoma.

Hemobilia is a rare manifestation of hepatic malignancies. The current treatment of choice for hemobilia is transcatheter hepatic arterial embolization. However, there have been only two published reports that describe the use of hepatic arterial embolization for hemobilia caused by hepatic neoplasms. In addition, this procedure is occasionally unsuccessful in the treatment of hemobilia. A case in which hemobilia caused by hepatocellular carcinoma was successfully treated with percutaneous radiofrequency tumor ablation after several failed hepatic arterial embolizations is described in this report.