Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry.

PURPOSE: To determine overall survival (OS), best response, and toxicities in patients with hepatocellular carcinoma (HCC) previously treated with chemoembolization (TACE+) or yttrium-90 resin transarterial radioembolization (TARE) compared with those of TACE-naïve (T-N) participants. MATERIALS AND METHODS: In this prospective, observational study, 262 adult participants with HCC were divided into TACE+ (n = 93, 35%) or T-N (n = 169, 65%) groups, included from 36 centers in the United States. Overall survival (OS) was assessed using Kaplan-Meier analysis from the date of TARE. Best response at 6 months was evaluated using modified Response Evaluation Criteria in Solid Tumors. Six-month toxicities were reported using Common Terminology Criteria for Adverse Events, version 5. RESULTS: Median OS for patients in the TACE+ and T-N groups was 22.3 months (95% CI: 17.2 to not reachable) and 21.5 months (95% confidence interval [CI]: 14.9-29.9), respectively (P = .6). Imaging at 6 months ± 2 weeks was available in 156 of 262 (60%) participants. Partial or complete response was seen in 27 of 55 patients (49%) in the TACE+ group and 65 of 101 patients (64%) in the T-N group (P = .2). Six-month toxicities were available in 69 of 93 patients (74%) in the TACE+ group and 135 of 167 patients (81%) in the T-N group. Attributable Grade 3 or greater liver function toxicities were similar between the study groups (all P > .05). CONCLUSIONS: OS and imaging response at 6 months in the TACE+ group was similar to that in the T-N group with similar toxicities. Radioembolization is an acceptable treatment option for patients with HCC previously treated with TACE.

Overall survival and toxicity of hepatocellular carcinoma Barcelona Clinic Liver Cancer B patients receiving Y90 radioembolization: analysis of the radiation-emitting SIR-spheres in non-resectable liver tumor (RESiN) registry.

Background: To evaluate overall survival (OS), progression-free survival (PFS) and toxicity after resin Yttrium-90 (Y-90) radioembolization in Barcelona Clinic Liver Cancer B (BCLC B) hepatocellular carcinoma (HCC) patients using the Bolondi subgroup classification. Methods: A total of 144 BCLC B patients were treated between 2015-2020. Patients were broken into 4 subgroups by tumor burden/liver function tests with 54, 59, 8 and 23 in subgroups 1, 2, 3 and 4. OS and PFS were calculated with Kaplan-Meier analysis with 95% confidence intervals. Toxicities were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5. Results: Prior resection and chemoembolization were performed in 19 (13%) and 34 (24%) of patients. There were no deaths within 30 days. Median OS and PFS for the cohort were 21.5 and 12.4 months. Median OS was not reached for subgroup 1 at a mean 28.8 months, and was 24.9, 11.0 and 14.6 months for subgroups 2-4 (χ2=19.8, P=0.0002). PFS by BCLC B subgroup was 13.8, 12.4, 4.5, and 6.6 months (χ2=16.8, P=0.0008). The most common Grade 3 or 4 toxicities were elevated bilirubin (n=16, 13.3%) and decreased albumin (n=15, 12.5%). Grade 3 or greater bilirubin (32% vs. 10%, P=0.03) and albumin (26% vs. 10%, P=0.03) toxicity were more common in the subgroup 4 patients. Conclusions: The Bolondi subgroup classification stratifies OS, PFS and development of toxicity in patients treated with resin Y-90 microspheres. OS in subgroup 1 approaches 2.5 years and Grade 3 or greater hepatic toxicity profile in subgroups 1-3 is low.

Cabozantinib plus durvalumab in advanced gastroesophageal cancer and other gastrointestinal malignancies: Phase Ib CAMILLA trial results.

This is the phase Ib part of the phase I/II CAMILLA trial evaluating cabozantinib plus durvalumab in advanced chemo-refractory proficient mismatch repair or microsatellite stable (pMMR/MSS) gastrointestinal malignancies including gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma, colorectal cancer (CRC), and hepatocellular carcinoma (HCC). Thirty-five patients are enrolled. There are no observed dose-limiting toxicities during dose escalation. The overall grade 3/4 treatment-related adverse event rate is 34%. Among evaluable patients (n = 30), the objective response rate (ORR) is 30%, disease control rate (DCR) 83.3%, 6-month progression-free survival (PFS) 36.7%, median PFS 4.5 months, and median overall survival (OS) 8.7 months. Responses are seen in 4 of 17, 3 of 10, and 2 of 3 patients with CRC, G/GEJ/E adenocarcinoma, and HCC, respectively. Participants with a PD-L1 combined positive score (CPS) ≥5 have numerically higher ORR, PFS, and OS. Cabozantinib plus durvalumab demonstrates a tolerable safety profile and potential efficacy in previously treated advanced pMMR/MSS gastrointestinal malignancies.

Survival and Toxicities after Yttrium-90 Transarterial Radioembolization of Cholangiocarcinoma in the RESiN Registry.

PURPOSE: To report outcomes in patients with intrahepatic cholangiocarcinoma treated with yttrium-90 resin microspheres (transarterial radioembolization [TARE]) from a multicenter, prospective observational registry. MATERIALS AND METHODS: Ninety-five patients (median age, 67 years [interquartile range {IQR}, 59-74]; 50 men) were treated in 27 centers between July 2015 and August 2020. Baseline demographic characteristics included imaging findings, performance status, and previous systemic or locoregional treatments. Dosimetry method was tracked. Overall survival (OS) and progression-free survival were calculated using the Kaplan-Meier method. The best imaging response was calculated using the Response Evaluation Criteria in Solid Tumors v1.1. Grade ≥3 toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox regression analysis was performed. RESULTS: Fifty-two of 86 (60%) patients had multifocal tumors, and 24/89 (27%) had extrahepatic tumors. The median index tumor diameter was 7.0 cm (IQR, 4.9-10 cm). The activity calculation method was reported in 59/95 (62%) patients, with body surface area being the most frequently used method (45/59, 76%). Median OS for the cohort was 14 months (95% confidence interval, 12-22). OS at 3, 6, 12, and 24 months was 94%, 80%, 63%, and 34%, respectively. Median OS was longer in patients without cirrhosis (19.1 vs 12.2 months, P = .05). Cirrhosis, previous chemotherapy (OS, 19.1 vs 10.6 months for treatment-naïve; P = .07), and imaging response at 6 months (OS, 16.4 vs 9.5 months for no response; P = .06) underwent regression analysis. Imaging response predicted OS at regression (hazard ratio, 0.39; P = .008). Grade 3-4 bilirubin toxicities were noted in 5 of 72 (7%) patients. Grade 3 albumin toxicity was noted in 1 of 72 (1.4%) patients. CONCLUSIONS: Objective response at 6 months predicted longer OS after TARE for intrahepatic cholangiocarcinoma. The incidence of liver function toxicity was <10%.

Overall survival and toxicity of Y90 radioembolization for hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C (BCLC-C).

INTRODUCTION: National Comprehensive Cancer Network HCC guidelines recommend Y90 to treat BCLC-C patients only in select cases given the development of systemic regimens. We sought to identify ideal candidates for Y90 by assessing survival and toxicities in this patient group. MATERIALS AND METHODS: The Radiation-Emitting Selective Internal radiation spheres in Non-resectable tumor registry is a prospective observational study (NCT: 02,685,631). Patients with advanced HCC were stratified into 3 groups based on tumor location, Eastern Cooperative Oncology Group (ECOG) performance status, and liver function. Group 1: liver isolated HCC, ECOG 0 and Child Pugh (CP) A (n = 12, 16%), Group 2: liver isolated HCC, ECOG ≥ 1 or CP B/C (n = 37, 49%), and Group 3: extrahepatic HCC with any ECOG or CP score (n = 26, 35%). Patients in any group could have macrovascular invasion. Overall survival (OS) and progression-free survival (PFS) with 95% confidence intervals (95% CI) were calculated. Grade 3 + toxicities were tracked using Common Terminology Criteria for Adverse Events v5. Cox proportional hazard model was performed to determine factors affecting OS. RESULTS: Seventy-five BCLC-C patients treated between 2015 and 2019 were reviewed. The groups were similar in age, sex, race, and ethnicity (all p > 0.05). Bilobar disease was least common in Group 1 (p < 0.001). Median OS of the entire cohort was 13.6 (95% CI 7.5-16.1) months. Median OS of Groups 1-3 were 21.8, 13.1 and 11.5 months respectively (p = 0.6). Median PFS for the cohort was 6.3 (4.8-14.7) months. Median PFS for group 1 was not reached. Mean PFS for Group 1 was 17.3 ± 4.8 months. Median PFS for Groups 2 and 3 was 6.8 and 5.9 months (X2 = 1.5, p = 0.5). Twenty-four Grade 3 or greater toxicities developed, most commonly hyperbilirubinemia (8/75, 11%) and thrombocytopenia (2/75, 3%). The incidence of toxicities between groups was similar (all p > 0.05). Cox Proportional Hazard analysis predicted shorter OS with CP class B/C (X2 = 6.7, p = 0.01), while macrovascular invasion (X2 = 0.5, p = 0.5) and ECOG score of ≥ 1 (X2 = 2.1, p = 0.3) was not associated with OS. CONCLUSIONS: OS of CPA patients with advanced HCC and performance status of 0 was 21.8 months following Y90. CP A cirrhosis is the best predictor of prolonged OS in advanced (BCLC-C) HCC.

Survival and Toxicities after 90Y Transarterial Radioembolization of Metastatic Colorectal Cancer in the RESIN Registry.

Background Patients with unresectable, chemorefractory hepatic metastases from colorectal cancer have considerable mortality. The role of transarterial radioembolization (TARE) with yttrium 90 (90Y) microspheres is not defined because most reports are from a single center with limited patient numbers. Purpose To report outcomes in participants with colorectal cancer metastases treated with resin 90Y microspheres from a prospective multicenter observational registry. Materials and Methods This study treated enrolled adult participants with TARE using resin microspheres for liver-dominant metastatic colorectal cancer at 42 centers, with enrollment from July 2015 through August 2020. TARE was used as the first-, second-, or third-line therapy or beyond. Overall survival (OS), progression-free survival (PFS), and toxicity outcomes were assessed by line of therapy by using Kaplan-Meier analysis for OS and PFS and Common Terminology Criteria for Adverse Events, version 5, for toxicities. Results A total of 498 participants (median age, 60 years [IQR, 52-69 years]; 298 men [60%]) were treated. TARE was used in first-line therapy in 74 of 442 participants (17%), second-line therapy in 180 participants (41%), and third-line therapy or beyond in 188 participants (43%). The median OS of the entire cohort was 15.0 months (95% CI: 13.3, 16.9). The median OS by line of therapy was 13.9 months for first-line therapy, 17.4 months for second-line therapy, and 12.5 months for third-line therapy (χ2 = 9.7; P = .002). Whole-group PFS was 7.4 months (95% CI: 6.4, 9.5). The median PFS by line of therapy was 7.9 months for first-line therapy, 10.0 months for second-line therapy, and 5.9 months for third-line therapy (χ2 = 8.3; P = .004). TARE-attributable grade 3 or 4 hepatic toxicities were 8.4% for bilirubin (29 of 347 participants) and 3.7% for albumin (13 of 347). Grade 3 and higher toxicities were greater with third-line therapy for bilirubin (P = .01) and albumin (P = .008). Conclusion Median overall survival (OS) after transarterial radioembolization (TARE) with yttrium 90 microspheres for liver-dominant metastatic colorectal cancer was 15.0 months. The longest OS was achieved when TARE was part of second-line therapy. Grade 3 or greater hepatic function toxicity rates were less than 10%. Clinical trial registration no. NCT02685631 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Long-term outcomes following 90Y Radioembolization of neuroendocrine liver metastases: evaluation of the radiation-emitting SIR-spheres in non-resectable liver tumor (RESiN) registry.

BACKGROUND: The goal of this study was to evaluate efficacy and safety of 90Y radioembolization for neuroendocrine liver metastases (NELM) in a multicenter registry. METHODS: One hundred-seventy patients with NELM were enrolled in the registry (NCT02685631). Prior treatments included hepatic resection (n = 23, 14%), arterial therapy (n = 62, 36%), octreotide (n = 119, 83%), cytotoxic chemotherapy (n = 58, 41%), biologic therapy (n = 49, 33%) and immunotherapy (n = 10, 6%). Seventy-seven (45%) patients had extrahepatic disease. Seventy-eight (48%), 61 (37%), and 25 (15%) patients were Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or ≥ 2. Tumor grade was known in 81 (48%) patients: 57 (70%) were well-, 12 (15%) moderate-, and 12 (15%) poorly-differentiated. Kaplan-Meier analysis and log rank tests were performed to compare overall and progression-free survival (OS/PFS) by tumor location and grade. Toxicities were reported using Common Terminology Criteria for Adverse Events v.5. Cox Proportional Hazards were calculated for pancreatic primary, performance status, extrahepatic disease at treatment, unilobar treatment, baseline ascites, and > 25% tumor burden. RESULTS: One, 2, and 3-year OS rates were 75, 62 and 46%, respectively. Median OS was 33 months [(95% CI: 25-not reached (NR)]. The longest median OS was in patients with pancreatic (42 months, 95% CI: 33-NR) and hindgut 41 months, 95% CI: 12-NR) primaries. The shortest OS was in foregut primaries (26 months; 95% CI: 23-NR; X2 = 7, p = 0.1). Median OS of well-differentiated tumors was 36 months (95% CI: 10-NR), compared to 44 (95% CI: 7-NR) and 25 (95% CI: 3-NR) months for moderate and poorly differentiated tumors. Median progression-free survival (PFS) was 25 months with 1, 2, and 3-year PFS rates of 70, 54, and 35%, respectively. Thirteen patients (7.6%) developed grade 3 hepatic toxicity, most commonly new ascites (n = 8, 5%) at a median of 5.5 months. Performance status of ≥2 (HR 2.7, p = 0.01) and baseline ascites (HR 2.8, P = 0.049) predicted shorter OS. DISCUSSION: In a population with a high incidence of extrahepatic disease, 90Y was effective and safe in treatment of NELM, with median OS of 41 months for well differentiated tumors. Grade 3 or greater hepatic toxicity was developed in 7.6% of patients. TRIAL REGISTRATION: NCT02685631 .

A case of two shunts in the endovascular treatment of type II Abernethy syndrome.

BACKGROUND: Abernethy malformation is a rare condition defined by a congenital extrahepatic portosystemic shunt, often leading to absence or hypoplasia of the intrahepatic portal venous system. Although there are no consensus treatment guidelines, interventional techniques now offer minimally invasive treatment options for Abernethy malformations. This case report describes a case of Abernethy Syndrome Type II where the patient had two separate extrahepatic portosystemic shunts treated with endovascular occlusion with two Amplatzer plugs and demonstrates the feasibility of this treatment for this rare condition. This case was in a young adult, adding to the scarce literature of treatment for Abernethy syndrome in the adult population. CASE PRESENTATION: We report a case of a 20-year-old female patient with neurocognitive behavioral difficulty, voracious appetite, and chronic encephalopathy secondary to type II Abernethy malformation with not one, but two extrahepatic portosystemic shunts. The patient had failed medical management and was not a liver transplant candidate. Therefore, she presented to us for an endovascular treatment option. The two shunts were treated with endovascular occlusion using Amplatzer vascular plugs. Following embolization, flow into the hypoplastic portal vein improved with near complete occlusion of flow into the portosystemic shunts, thus restoring blood flow into the native portal system. At 3 month follow up, a CT demonstrated complete occlusion of the two portosystemic shunts, and a portal vein diminutive in caliber. The portal vein measured 7 mm in diameter on both pre and post-procedure CT scans. The total volume of the liver was found to be 843 cm3 on pre-procedure CT & 1191 cm3 on post-procedure CT. CONCLUSIONS: This report demonstrates the feasibility of using endovascular embolization to treat Abernethy II malformations. The management strategy of Type II Abernethy Syndrome should be to redirect blood flow into the hypoplastic native portal system, allowing for physiologic hepatic metabolism of splanchnic blood, hypertrophy of the portal system, and growth of the liver from the increased trophic flow.

Do Video Games Predict an Early Advanced Capacity to Learn Interventional Radiology Skills?

PURPOSE: To elucidate the relationship between video game (VG) play and interventional radiology (IR) technical skills in medical students. MATERIALS AND METHODS: Twenty medical students recruited at our institution's IR symposium completed a survey to ascertain demographics and prior VG experience, then participated in a 3-part trial of skills assessing IR and VG skill and visuospatial aptitude (VSA). IR skill was evaluated via an endovascular simulation task, VG skill by performance on three separate VGs, and VSA using the Cube Comparison test. Regression analysis was tested the strength of relationship between IR skill and VG experience, VG skill, and VSA, respectively, and participants were stratified by IR skill to top and bottom halves for survey-response comparison. RESULTS: There was no correlation between either VG skill or visuospatial aptitude and IR skill (r = -0.22, p = 0.35; and r = 0.14, p = 0.57). Greater number of years playing VGs correlated with superior IR skill (Spearman's rho=-0.45, p<0.05). Students who selected IR as their specialty of interest had extensive VG experience, playing for > 15 years (n = 4, 80%), at least 10 hours per week at their peak (n = 3, 60%), and reported being either "skilled" or "highly skilled" at VGs (n = 3, 60%). CONCLUSIONS: In our study, though limited by power, number of years playing VGs correlated positively with IR skills in medical students. Prior VG experience may predict an early advanced capacity to learn IR skills and an interest in the specialty.

Lidocaine Versus Bupivacaine in the Treatment of Headache with Intranasal Sphenopalatine Nerve Block.

BACKGROUND: Intranasal sphenopalatine ganglion (SPG) block has been shown to be an effective treatment for headaches. Multiple therapeutic agents have been studied, although the wide availability and low cost of lidocaine and bupivacaine have made them attractive treatment options. To the authors knowledge, no study has yet demonstrated superiority of one anesthetic over the other. OBJECTIVE: To determine the efficacy of lidocaine versus bupivacaine when performing intranasal sphenopalatine ganglion (SPG) block for the treatment of headaches. STUDY DESIGN: Retrospective cohort study. SETTING: A single tertiary care academic institutionMETHODS: This retrospective study identified patients who underwent SPG block at a single institution from January 1, 2014 to December 20, 2017. Patients were included if they were treated with either lidocaine or bupivacaine and had both pre- and post-procedure pain scores recorded on a 0-10 scale. Patients were excluded if they were less than 18 years of age. RESULTS: 386 total procedures were performed. 303 (78.5%) were lidocaine delivered via the SphenoCath device, and 83 (21.5%) were bupivacaine delivered via the Tx360 device. 90.2% of treatments (n = 348) decreased the patient's pain level. Of the treatments performed with lidocaine, 89.1% (n = 270) resulted in improvement of the patient's pain level with a mean decrease in pain level of 3.1 (SD ± 2.3). Of the treatments performed with bupivacaine, 94.0% (n = 78) resulted in improvement of the patient's pain level, with a mean decrease in pain level of 3.0 (SD ± 1.9). No statistically significant difference was found between the 2 anesthetics. LIMITATIONS: The retrospective study design may introduce selection bias. Both lidocaine and bupivacaine were administered by different devices (Sphenocath and Tx360 respectively) which may account for differences in initial treatment success. There were differences in the size of the two groups, which may also introduce error. CONCLUSIONS: This study demonstrates similar efficacy of SPG block performed with lidocaine or bupivacaine. While no difference was found, the particular advantages and disadvantages of the intranasal delivery device may influence physician choice. KEY WORDS: Sphenopalatine ganglion nerve block, lidocaine, bupivacaine, sphenocath, Tx360, pain intervetnio, headache, miimally invasive therapy.

Successful Percutaneous Treatment of an Arteriovenous Malformation of the Toe.

Arteriovenous malformations (AVMs) of the toe are a rare entity. To the author's knowledge, there are only 2 published case reports, and both patients underwent amputation of the affected digits. Little is known about the optimal treatment of AVMs involving the toe. The authors present the case of a 20-year-old male with a large AVM of the second toe, which was successfully treated with intra-arterial sodium tetradecyl sulfate. Percutaneous treatment of these lesions is possible and should be considered before amputation.

Case report: interventional radiology's potential role for in vitro fertilization post ovarian transposition and pelvic radiation.

INTRODUCTION: Ovarian transposition is a procedure that can help preserve fertility for female patients requiring radiation in the abdominopelvic region. However, the displacement of ovaries from its original anatomic location can make oocyte retrieval challenging. CASE PRESENTATION: A 24-year-old nulligravid patient recently diagnosed with colorectal carcinoma [CRC] underwent ovarian transposition prior to radiation. After radiation and chemotherapy, she began in vitro fertilization [IVF] by reproductive endocrinology and infertility physicians. Right ovary demonstrated nonviability due to failed transposition and radiation. Left ovarian oocytes were not able to be harvested due to risk of left kidney puncture via transvaginal ultrasound [TVUS]. Interventional Radiology [IR] was involved and performed a transabdominal ultrasound guided egg retrieval which led to successful IVF. CONCLUSION: This case highlights the utility of IR-assisted transabdominal ultrasound approach for oocyte retrieval in patients with history of ovarian transposition.

MRI findings of absorbable hydrogel spacer for prostate cancer therapy: a pictorial review.

Prior studies have shown that dose-escalated radiation therapy for prostate cancer improves clinical outcomes. However, this is associated with increased rectal toxicity. Hydrogel spacer for prostate cancer therapy is an effective way of decreasing rectal toxicity in the late post-therapeutic stages. In some occasions, the gel spacer may not be placed symmetrically between the rectum and prostate. There are several forms of a malpositioned spacer, including lateral displacement, rectal wall infiltration, and prostate capsule infiltration. This manuscript is aimed at evaluating appropriately positioned and malpositioned gel spacers, primarily via magnetic resonance imaging. There are limited educational imaging guides that address what radiologists should evaluate on post-spacer placement imaging. This pictorial review will specifically evaluate post-injection pitfalls such as asymmetry, rectal wall infiltration, and subcapsular injection.

The Utility of a Benign Biliary Stricture Protocol in Preventing Symptomatic Recurrence and Surgical Revision.

PURPOSE: To determine whether treating benign biliary strictures via a stricture protocol reduced the probability of developing symptomatic recurrence and requiring surgical revision compared to nonprotocol treatment. MATERIALS AND METHODS: A stricture protocol was designed to include serial upsizing of internal/external biliary drainage catheters to a target maximum dilation of 18-French, optional cholangioplasty at each upsizing, and maintenance of the largest catheter for at least 6 months. Patients were included in this retrospective analysis if they underwent biliary ductal dilation at a single institution from 2005 to 2016. Forty-two patients were included, 25 women and 17 men, with an average age of 51.9 years (standard deviation ± 14.6). Logistic regression models were used to determine the probability of symptomatic recurrence and surgical revision by stricture treatment type. RESULTS: Twenty-two patients received nonprotocol treatment, while 20 received treatment on a stricture protocol. After treatment, 7 (32%) patients in the nonprotocol group experienced clinical or laboratory recurrence of a benign stricture, whereas only 1 patient in the stricture protocol group experienced symptom recurrence. Patients in the protocol group were 8.9 times (95% confidence interval [CI] = 1.4-175.3) more likely to remain symptom free than patients in the nonprotocol group. Moreover, patients in the protocol group had an estimated 89% reduction in the probability of undergoing surgical revision compared to patients receiving nonprotocol treatment (odds ratio = .11, 95% CI = .01-.73). CONCLUSIONS: Establishing a stricture protocol may decrease the risk of stricture recurrence and the need for surgical revision when compared to a nonprotocol treatment approach.

Divergent lactate dehydrogenase isoenzyme profile in cellular compartments of primate forebrain structures.

The compartmentalization and association of lactate dehydrogenase (LDH) with specific cellular structures (e.g., synaptosomal, sarcoplasmic or mitochondrial) may play an important role in brain energy metabolism. Our previous research revealed that LDH in the synaptosomal fraction shifts toward the aerobic isoforms (LDH-B) among the large-brained haplorhine primates compared to strepsirrhines. Here, we further analyzed the subcellular localization of LDH in primate forebrain structures using quantitative Western blotting and ELISA. We show that, in cytosolic and mitochondrial subfractions, LDH-B expression level was relatively elevated and LDH-A declined in haplorhines compared to strepsirrhines. LDH-B expression in mitochondrial fractions of the neocortex was preferentially increased, showing a particularly significant rise in the ratio of LDH-B to LDH-A in chimpanzees and humans. We also found a significant correlation between the protein levels of LDH-B in mitochondrial fractions from haplorhine neocortex and the synaptosomal LDH-B that suggests LDH isoforms shift from a predominance of A-subunits toward B-subunits as part of a system that spatially buffers dynamic energy requirements of brain cells. Our results indicate that there is differential subcellular compartmentalization of LDH isoenzymes that evolved among different primate lineages to meet the energy requirements in neocortical and striatal cells.

Differences in Radiation Activity Between Glass and Resin 90Y Microspheres in Treating Unresectable Hepatic Cancer.

The purpose of this study was to compare the difference in prescribed radiation activity between glass and resin yttrium-90 (Y) microspheres for radioembolization of unresectable hepatocellular carcinoma (HCC) or liver metastases at a tertiary care teaching institution. The authors performed a retrospective analysis on 126 patients with primary HCC and hepatic metastatic disease from extrahepatic primary cancers who underwent radioembolization with glass or resin particles between 2008 and 2013 at their institution. Radiation activity estimates for prescribed treatments, as well as for the alternate embolization particles, were calculated using commonly employed formulae for both glass and resin particles for all treatments. A total of 217 treatments were performed on 126 patients, with 136 (62.7%) using glass particles and 81 (37.3%) using resin particles. Forty-six (36.5%) patients had metastatic colorectal cancer (CRC), 51 (40.5%) had primary HCC, while 11 (8.7%) had neuroendocrine carcinoma, and 18 (14.3%) had metastases from other primary tumors. The average prescribed activity was 2.66 GBq for glass treatments and 1.06 GBq for resin treatments across all cancer types. When the alternative treatment activity was calculated, activities were projected to decrease by an average of 1.52 GBq per treatment if resin microspheres were used instead of glass microspheres (-52.5%), while activities were projected to increase by an average of 1.57 GBq per treatment if glass microspheres were used instead of resin microspheres (148.9%; p < 0.001). Similar results were seen within each malignancy type and all projected changes were statistically significant (p < 0.001). In conclusion, prescribed radiation activity for radioembolization of unresectable hepatic cancer was significantly lower for resin compared to glass microspheres.

Synaptosomal lactate dehydrogenase isoenzyme composition is shifted toward aerobic forms in primate brain evolution.

With the evolution of a relatively large brain size in haplorhine primates (i.e. tarsiers, monkeys, apes, and humans), there have been associated changes in the molecular machinery that delivers energy to the neocortex. Here we investigated variation in lactate dehydrogenase (LDH) expression and isoenzyme composition of the neocortex and striatum in primates using quantitative Western blotting and isoenzyme analysis of total homogenates and synaptosomal fractions. Analysis of isoform expression revealed that LDH in synaptosomal fractions from both forebrain regions shifted towards a predominance of the heart-type, aerobic isoform LDH-B among haplorhines as compared to strepsirrhines (i.e. lorises and lemurs), while in the total homogenate of the neocortex and striatum there was no significant difference in LDH isoenzyme composition between the primate suborders. The largest increase occurred in synapse-associated LDH-B expression in the neocortex, with an especially remarkable elevation in the ratio of LDH-B/LDH-A in humans. The phylogenetic variation in the ratio of LDH-B/LDH-A was correlated with species-typical brain mass but not the encephalization quotient. A significant LDH-B increase in the subneuronal fraction from haplorhine neocortex and striatum suggests a relatively higher rate of aerobic glycolysis that is linked to synaptosomal mitochondrial metabolism. Our results indicate that there is a differential composition of LDH isoenzymes and metabolism in synaptic terminals that evolved in primates to meet increased energy requirements in association with brain enlargement.

Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans.

Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks in mid-childhood, with subsequent pruning through early adulthood, as well as relatively delayed maturation of neuronal arborization in the prefrontal cortex compared with sensorimotor areas. In macaque monkeys, cortical synaptogenesis peaks during early infancy and developmental changes in synapse density and dendritic spines occur synchronously across cortical regions. Thus, relatively prolonged synapse and neuronal maturation in humans might contribute to enhancement of social learning during development and transmission of cultural practices, including language. However, because macaques, which share a last common ancestor with humans ≈ 25 million years ago, have served as the predominant comparative primate model in neurodevelopmental research, the paucity of data from more closely related great apes leaves unresolved when these evolutionary changes in the timing of cortical development became established in the human lineage. To address this question, we used immunohistochemistry, electron microscopy, and Golgi staining to characterize synaptic density and dendritic morphology of pyramidal neurons in primary somatosensory (area 3b), primary motor (area 4), prestriate visual (area 18), and prefrontal (area 10) cortices of developing chimpanzees (Pan troglodytes). We found that synaptogenesis occurs synchronously across cortical areas, with a peak of synapse density during the juvenile period (3-5 y). Moreover, similar to findings in humans, dendrites of prefrontal pyramidal neurons developed later than sensorimotor areas. These results suggest that evolutionary changes to neocortical development promoting greater neuronal plasticity early in postnatal life preceded the divergence of the human and chimpanzee lineages.