Albert A. Nemcek

A lexicon for endoscopic adverse events: report of an ASGE workshop

Patients and practitioners expect that their endoscopy procedures will go smoothly and according to plan. There are several reasons why they may be disappointed. The procedure may fail technically (eg, incomplete colonoscopy, failed biliary cannulation). It may seem to be successful technically but turn out to be clinically unhelpful (eg, a diagnosis missed, an unsuccessful treatment), or there may be an early relapse (eg, stent dysfunction). In addition, some patients and relatives may be disappointed by a lack of courtesy and poor communication, even when everything otherwise works well. The most feared negative outcome is when something ‘‘goes wrong’’ and the patient experiences a ‘‘complication.’’ This term has unfortunate medicolegal connotations and is perhaps better avoided. Describing these deviations from the plan as ‘‘unplanned events’’ fits nicely

Safety and Efficacy of 90Y Radiotherapy for Hepatocellular Carcinoma With and Without Portal Vein Thrombosis

This study was undertaken to present data from a phase 2 study in which patients with unresectable hepatocellular carcinoma (HCC) with and without portal vein thrombosis underwent radioembolization with Yttrium (90Y) microspheres. Patients treated were stratified by Okuda, Child‐Pugh, baseline bilirubin, tumor burden, Eastern Cooperative Oncology Group (ECOG), presence of cirrhosis and portal vein thrombosis (PVT) (none, branch, and main). Clinical and biochemical data were obtained at baseline and at 4‐week intervals following treatment for up to 6 months. Tumor response was obtained using computed tomography (CT). Patients were followed for survival. One hundred eight patients were treated during the study period. Thirty‐seven (34%) patients had PVT, 12 (32%) of which involved the main PV. The cumulative dose for those with and without PVT was 139.7 Gy and 131.9 Gy, respectively. The partial response rate using world Health Organization (WHO) criteria was 42.2%. Using European Association for the Study of the Liver (EASL), the response rate was 70%. Kaplan‐Meier survival varied depending on location of PVT and presence of cirrhosis. The adverse event (AE) rates were highest in patients with main PVT and cirrhosis. There were no cases of radiation pneumonitis. Conclusion: The use of minimally embolic 90Y glass microspheres to treat patients with HCC complicated by branch/lobar PVT may be clinically indicated and appears to have a favorable toxicity profile. Further investigation is warranted in patients with main PVT. (HEPATOLOGY 2007.)

Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma

BACKGROUND & AIMS Chemoembolization is one of several standards of care treatment for hepatocellular carcinoma (HCC). Radioembolization with Yttrium-90 microspheres is a novel, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. METHODS We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up time points. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multivariate analyses were performed. RESULTS Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P < .05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs 36%, respectively, P = .104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, respectively, P = .046), median survival times were not statistically different (20.5 months vs 17.4 months, respectively, P = .232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P = .42). CONCLUSIONS Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post hoc analyses of sample size indicated that a randomized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies.

Current management of visceral artery aneurysms

BACKGROUND Visceral artery aneurysms are an uncommon but important form of abdominal vascular disease. This study reviews a contemporary experience with special emphasis on newer methods of diagnosis and treatment. METHODS From 1980 to 1994, 37 patients were diagnosed with 46 visceral artery aneurysms. These consisted of 22 splenic, 10 hepatic, 4 superior mesenteric, 2 gastroduodenal, 3 celiac, 2 left gastric, 1 pancreatoduodenal, 1 jejunal-ileal, and 1 inferior mesenteric artery aneurysms. Follow-up was complete for 28 patients, average of 37.7 months. There were 17 asymptomatic and 29 symptomatic aneurysms, including 11 presenting with rupture. RESULTS Seventeen patients were treated surgically, with no surgical deaths. Surgical complications included splenic abscess (two) and failure to thrombose (one). Transcatheter embolization was used in 12 patients. Complications included splenic infarction (one) and recurrence (two), successfully treated with repeat embolization. Nine patients were treated with observation. Eight experienced no complications during follow-up; one died of a ruptured splenic artery aneurysm before treatment was initiated. CONCLUSIONS The widespread use of computed tomography has led to increased detection of asymptomatic visceral artery aneurysms. Although surgery remains necessary in many patients, transcatheter embolization is effective in the treatment of selected visceral artery aneurysms with few complications and low recurrence.

Radioembolization with 90Y Microspheres: Angiographic and Technical Considerations

The anatomy of the mesenteric system and the hepatic arterial bed has been demonstrated to have a high degree of variation. This is important when considering pre-surgical planning, catheterization, and trans-arterial hepatic therapies. Although anatomical variants have been well described, the characterization and understanding of regional hepatic perfusion in the context of radioembolization have not been studied with great depth. The purpose of this review is to provide a thorough discussion and detailed presentation of the angiographic and technical aspects of radioembolization. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. Furthermore, the principles described here apply to all liver-directed transarterial therapies.

Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival.

PURPOSE To prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with yttrium 90 ((90)Y) glass microspheres. MATERIALS AND METHODS Institutional review boards from two institutions approved the HIPAA-compliant study; all patients provided informed consent. One hundred thirty-seven patients underwent 225 administrations of (90)Y microspheres by using intraarterial infusion. Primary sites (origins) included colon, breast, neuroendocrine, pancreas, lung, cholangiocarcinoma, melanoma, renal, esophageal, ovary, adenocarcinoma of unknown primary, lymphoma, gastric, duodenal, bladder, angiosarcoma, squamous cell carcinoma, thyroid, adrenal, and parotid. Patients underwent evaluation of baseline and follow-up liver function and tumor markers and computed tomographic or magnetic resonance imaging. Patients were observed for survival from first treatment. Median survival (in days) and corresponding 95% confidence intervals were computed by using the Kaplan-Meier method. The log-rank statistic was used for statistical significance testing of survival distributions between various subgroups of patients. RESULTS There were 66 men and 71 women. All patients were treated on an outpatient basis. Median age was 61 years. The mean number of treatments was 1.6. The median activity and dose infused were 1.83 GBq and 112.8 Gy, respectively. Clinical toxicities included fatigue (56%), vague abdominal pain (26%), and nausea (23%). At follow-up imaging, according to World Health Organization criteria, there was a 42.8% response rate (2.1% complete response, 40.7% partial response). There was a biologic tumor response (any decrease in tumor size) of 87%. Overall median survival was 300 days. One-year survival was 47.8%, and 2-year survival was 30.9%. Median survival was 457 days for patients with colorectal tumors, 776 days for those with neuroendocrine tumors, and 207 days for those with noncolorectal, nonneuroendocrine tumors. CONCLUSION (90)Y hepatic treatments are well tolerated with acceptable toxicities; tumor response and median survival are promising.

Phase II trial of chemoembolization for the treatment of metastatic colorectal carcinoma to the liver and review of the literature

Hepatic artery chemoembolization represents an alternative treatment for patients whose neoplastic lesions are not amenable or have become refractory to other treatment modalities. This project was designed to test the feasibility of regional chemoembolization for patients with colorectal carcinoma metastasis to the liver who had experienced failure with one or more systemic treatments.

Treatment of Unresectable Primary and Metastatic Liver Cancer with Yttrium-90 Microspheres (TheraSphere®): Assessment of Hepatic Arterial Embolization

In Canada and Europe, yttrium-90 microspheres (TheraSphere®; MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.

Chemoembolization for Hepatocellular Carcinoma: Comprehensive Imaging and Survival Analysis in a 172-Patient Cohort

PURPOSE To determine comprehensive imaging and long-term survival outcome following chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS One hundred seventy-two patients with HCC treated with chemoembolization were studied retrospectively in an institutional review board approved protocol; this study was HIPAA compliant. Baseline laboratory and imaging characteristics were obtained. Clinical and laboratory toxicities following treatment were assessed. Imaging characteristics following chemoembolization were evaluated to determine response rates (size and necrosis) and time to progression (TTP). Survival from the time of first chemoembolization treatment was calculated. Subanalyses were performed by stratifying the population according to Child-Pugh, United Network for Organ Sharing, and Barcelona Clinic for Liver Cancer (BCLC) staging systems. RESULTS Cirrhosis was present in 157 patients (91%); portal hypertension was present in 139 patients (81%). Eleven patients (6%) had metastases at baseline. Portal vein thrombosis was present in 11 patients (6%). Fifty-five percent of patients experienced some form of toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. Post-chemoembolization response was seen in 31% and 64% of patients according to size and necrosis criteria, respectively. Median TTP was 7.9 months (95% confidence interval: 7.1, 9.4) but varied widely by stage. Median survival was significantly different between patients with BCLC stages A, B, and C disease (stage A, 40.0 months; B, 17.4 months; C, 6.3 months; P < .0001). CONCLUSION The determination of TTP and survival in patients with HCC is confounded by tumor biology and background cirrhosis; chemoembolization was shown to be a safe and effective therapy in patients with HCC.

Uterine Arteriovenous Malformations: Primary Treatment with Therapeutic Embolization

Uterine arteriovenous malformations are rare lesions that can cause massive vaginal bleeding and spontaneous abortions. The majority are either congenital or related to gestational trophoblastic disease. Hysterectomy has been the treatment with symptomatic uterine arteriovenous malformations by means of transcatheter embolization; three of the lesions were related to gestational trophoblastic disease and one was congenital. All were supplied by the uterine arteries that were subselectively embolized with particulate material. This resulted in prompt cessation of uterine hemorrhage. There were no complications, and one pregnancy was achieved. The three other women have normal menstruation and no recurrence of bleeding at follow-up 10-48 months after treatment. On the basis of this experience and that of others, embolotherapy should be the treatment of first choice in these lesions, as it appears safe and effective. Additionally, uterine function is preserved in patients who are usually reproductively active.