Intensive locoregional therapy before liver transplantation for colorectal cancer liver metastasis: A novel pretransplant protocol.

We describe a novel pre-liver transplant (LT) approach in colorectal liver metastasis, allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. Patients undergoing LT for colorectal liver metastasis at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by positron emission tomography scan and carcinoembryonic Ag. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. Nine patients received liver transplant out of 27 who were evaluated (33.3%). The median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease, and 4 had treatment-induced cirrhosis. Pretransplant management included chemotherapy (n = 9) +/- bevacizumab (n = 6) and/or anti-EGFR (n = 6). The median number of pre-LT cycles of chemotherapy was 16 (range 10-40). Liver-directed therapy included Yttrium-90 (n = 5), ablation (n = 4), resection (n = 4), and hepatic artery infusion pump (n = 3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n = 6/8) and 60% (n = 3/5). Recurrence occurred in the lungs (n = 1), liver graft (n = 1), and lungs+para-aortic nodes (n = 1). Patients with pre-LT detectable disease had reduced RFS ( p = 0.04). All patients with recurrence had histologically viable tumors in the liver explant. Patients treated in our protocol (n = 16) demonstrated improved survival versus those who were not candidates (n = 11) regardless of transplant status ( p = 0.01). A protocol defined by aggressive pretransplant liver-directed treatment and transplant for patients with the undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.

Emerging and Clinically Accepted Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.

Comparison of Perioperative Outcomes in Patients with Graves' Disease Undergoing Total Thyroidectomy With or Without Near Infrared Autofluorescence Imaging.

Background: The impact of near-infrared autofluorescence (NIRAF) imaging on postthyroidectomy hypocalcemia is controversial. As patients with Graves' disease are at increased risk, our aim was to compare postoperative parathyroid function in these patients undergoing total thyroidectomy (TT) with or without NIRAF imaging. Methods: This was a retrospective "before and after" study, comparing outcomes of patients who underwent TT without or with NIRAF imaging at a single center. Primary outcome was the incidence of temporary hypocalcemia and secondary outcomes, rates of incidental parathyroidectomy on final specimens and permanent hypocalcemia. Analyses were performed using Mann-Whitney U and chi-Square tests. Continuous data are expressed as median (interquartile range). Results: There were 85 patients in NIRAF and 100 patients in non-NIRAF group. Groups were comparable regarding age, gender, body-mass index, and thyroid weight. Number of parathyroid glands identified intraoperatively was 3 in both groups (p = 0.47). Intraoperative parathyroid implantation rate was 16.5% in NIRAF and 6% in non-NIRAF group (p = 0.02). Incidental parathyroidectomy rate on final pathology was 12.9% in NIRAF and 32% in non-NIRAF group (p = 0.002). The rates of temporary (11.7% vs. 16%) and permanent hypocalcemia (2.4% vs. 2%) were similar between the two groups, respectively (p = 0.66). Conclusion: To our knowledge, this is the first comparative study investigating the impact of NIRAF on postoperative parathyroid function after thyroidectomy for Graves' disease. The rate of incidental parathyroidectomy on final pathology was lower with use of NIRAF, without an impact on temporary or permanent hypocalcemia rates compared to conventional technique.

The utility of fluorescence imaging in detecting primary and metastatic small bowel carcinoid tumors.

BACKGROUND: Our aim was to investigate utility of indocyanine green (ICG) and autofluorescence (AF) imaging in detection of small bowel primary and metastatic carcinoids. METHODS: Using Institutional Review Board approval, ICG and AF imaging of small bowel carcinoids was performed. Imaging findings were prospectively recorded in operating room and compared with conventional imaging, surgical exploration and pathologic findings. RESULTS: There were 16 patients with 23 primary small bowel tumors, 27 mesenteric lymph nodes, 36 liver metastases and 2 peritoneal nodules. Carcinoid tumors exhibited brighter AF signals compared to background. AF imaging was superior to both DOTATATE PET and surgeon inspection/palpation in demonstrating small bowel primaries. Utility for metastatic lymph nodes and peritoneal metastases was limited. Superficial liver metastases exhibited brighter fluorescence compared to background on both ICG and AF imaging. CONCLUSIONS: This is the largest study assessing utility of near-infrared fluorescence imaging in detection of small bowel carcinoids. Our results show promise in the utilization fluorescence imaging to detect occult primary tumors and superficial liver metastases.

Effects of thiamethoxam on brain structure of Bombus terrestris (Hymenoptera: Apidae) workers.

Neonicotinoids are the most widely used pesticide compared to other major insecticide classes known worldwide and have the fastest growing market share. Many studies showed that neonicotinoid pesticides harm honeybee learning and farming activities, negatively affect colony adaptation and reduce pollination abilities. Bumblebees are heavily preferred species all over the world in order to ensure pollination in plant production. In this study, sublethal effects of the neonicotinoid insecticide thiamethoxam on the brain of Bombus terrestris workers were analyzed. Suspensions (1/1000, 1/100, 1/10) of the maximum recommended dose of thiamethoxam were applied to the workers. 48 h after spraying, morphological effects on the brains of workers were studied. According to area measurements of ICC's of Kenyon cells, there was a significant difference between 1/10 dose and all groups. On the other hand, areas of INC's of Kenyon cells showed a significant difference between the control group and all dose groups. Neuropil disorganization in the calyces increased gradually and differed significantly between the groups and was mostly detected at the highest dose (1/10). Apart from optic lobes, pycnotic nuclei were also observed in the middle region of calyces of mushroom bodies in the high dose group. Also, the width of the lamina, medulla and lobula parts of the optic lobes of each group and the areas of the antennal lobes were measured and significant differences were determined between the groups. The results of the study revealed that sublethal doses of thiamethoxam caused some negative impacts on brain morphology of B. terrestris workers.

Sublethal effects of thiamethoxam on immune system cells in the workers of Bombus terrestris (Hymenoptera: Apidae).

Neonicotinoids harm especially bumblebees and other species in agricultural areas all over the world. The toxic effect of thiamethoxam from the neonicotinoid group has been little studied especially on bees. This research aimed to evaluate the effects of thiamethoxam on the immune system cells of Bombus terrestris workers. Different ratios of 1/1000, 1/100 and 1/10 of the recommended maximum application dose of thiamethoxam formed the experimental groups. Ten foraging workers were used for each dose and control groups. Contamination was ensured by spraying the prepared suspensions at different ratios to the bees for 20 s at a pressure of 1 atm. The effects of thiamethoxam on the structures of immune system cells of bumblebees and the amount of these cells were investigated after 48 h of exposure. In general, anomalies such as vacuolization, cell membrane irregularities and cell shape changes were detected in prohemocyte, plasmatocyte, granulocyte, spherulocyte and oenocytoid in each dose group. Hemocyte area measurements in all groups were examined comparatively between groups. In general, granulocyte and plasmatocyte sizes were decreased, while spherulocyte and oenocytoid were increased. It was also determined that there was a significant decrease in the amount of hemocytes in the 1 mm3 hemolymph as dose increased. The results of the study revealed that sublethal doses of thiamethoxam negatively affected hemocytes and their amounts of B. terrestris workers.