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At least 73 records · Page 4

SU-F-J-225: Histology Study of MR Guided Pulsed Focused Ultrasound On Treatment of Prostate Cancer in Vivo

Purpose: Our previous study demonstrated significant tumor growth delay in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. The temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized at pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level using the DAB analysis software. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality may synergize with PARP inhibitors to achieve better therapeutic result.

60 APPLIED LIFE SCIENCES↗

Can MRI be used to diagnose histologic grade in T1a (< 4 cm) clear cell renal cell carcinomas?

Objective: To assess whether MRI can differentiate low-grade from high-grade T1a cc-RCC. Materials and methods: With IRB approval, 49 consecutive solid < 4 cm cc-RCC (low grade [Grade 1 or 2] N = 38, high grade [Grade 3] N = 11) with pre-operative MRI before nephrectomy were identified between 2013 and 2018. Tumor size, apparent diffusion coefficient (ADC) histogram analysis, enhancement wash-in and wash-out rates, and chemical shift signal intensity index (SI index) were assessed by a blinded radiologist. Subjectively, two blinded Radiologists also assessed for (1) microscopic fat, (2) homogeneity (5-point Likert scale), and (3) ADC signal (relative to renal cortex); discrepancies were resolved by consensus. Outcomes were studied using Chi square, multivariate analysis, logistic regression modeling, and ROC. Inter-observer agreement was assessed using Cohen’s kappa. Results: Tumor size was 24 ± 7 (13–39) mm with no association to grade (p = 0.45). Among quantitative features studied, corticomedullary phase wash-in index (p = 0.015), SI index (p = 0.137), and tenth-centile ADC (p = 0.049) were higher in low-grade tumors. 36.8% (14/38) low-grade tumors versus zero high-grade tumors demonstrated microscopic fat (p = 0.015; Kappa = 0.67). Microscopic fat was specific for low-grade disease (100.0% [71.5–100.0]) with low sensitivity (36.8% [21.8–54.6]). Other subjective features did not differ between groups (p > 0.05). A logistic regression model combining microscopic fat + wash-in index + tenth-centile-ADC yielded area under ROC curve 0.98 (Confidence Intervals 0.94–1.0) with sensitivity/specificity 87.5%/100%. Conclusion: The combination of microscopic fat, higher corticomedullary phase wash-in and higher tenth-centile ADC is highly accurate for diagnosis of low-grade disease among T1a clear cell RCC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Insights into the histology of planarian flatworm Phagocata gracilis based on location specific, intact lipid information provided by GCIB-ToF-SIMS imaging

Planarian flatworms are known as the masters of regeneration, re-growing an entire organism from as little as 1/279th part of their body. While the proteomics of these processes has been studied extensively, the planarian lipodome remains relatively unknown. In this study we investigate the lipid profile of planarian tissue sections with imaging Time-of-Flight – Secondary-Ion-Mass-Spectrometry (ToF-SIMS). ToF-SIMS is a label-free technique capable of gathering intact, location specific lipid information on a cellular scale. Lipid identities are confirmed using LC-MS/MS. Our data shows that different organ structures within planarians have unique lipid profiles. The 22-carbon atom poly unsaturated fatty acids (PUFAs) which occur in unusually high amounts in planarians are found to be mainly located in the testes. Additionally, we observe that planarians contain various odd numbered fatty acid species that are usually found in bacteria, localized in the reproductive and ectodermal structures of the planarian. An abundance of poorly understood ether fatty acids and ether lipids were found in unique areas in planarians as well as a new, yet unidentified class of potential lipids in planarian intestines. Identifying the location of these lipids in the planarian body provides insights into their bodily functions and, in combination with knowledge about their diet and their genome, enables drawing conclusions about planarian fatty acid processing.

Angerer, Tina B.↗

Evaluation of the use of common sculpin (Myoxocephalus scorpius) organ histology as bioindicator for element exposure in the fjord of the mining area Maarmorilik, West Greenland

The former Black Angel lead–zinc mine in Maarmorilik, West Greenland, is a historic example of how mining activity may result in a significant impact on the surrounding fjord system in terms of elevated concentrations of especially lead (Pb) and zinc (Zn) in seawater, sediments and surrounding biota. In order to shed light on the present contamination and possible effects in the fjord we initiated a range of studies including a pilot study on gill and liver morphology of common sculpins (Myoxocephalus scorpius) around Maarmorilik. Sculpins were caught and sampled at five different stations known to represent a gradient of Pb concentrations. Fish livers from all specimens were analyzed for relevant elements in the area: Fe, Zn, As, Cu, Se, Cd, Pb, Ag, Hg, Co and Ni. Lead, As and Hg showed significant differences among the five stations. For 20% of the sculpins, Hg concentrations were in the range of lowest observed effect dose (LOED) of 0.1–0.5 μg/g ww for toxic threshold on reproduction and subclinical endpoints. Likewise LOEDs for tissue lesions, LOEDs for biochemistry, growth, survival and reproduction were exceeded for Cd (0.42–1.8 μg/g ww) and for As (11.6 μg/g ww) in 28% and 85% of the sculpins, respectively. Similar to this, the no observed effect dose (NOED) for biochemistry was exceeded for Pb (0.32 μg/g ww) and for growth, mortality and reproduction for Zn (60–68 μg/g ww) in 33% and 24% of the sculpins, respectively. For all sculpins, females were significantly larger than males and for five of the elements (Fe, Co, Ni, Cu, Se) females had higher concentrations. The chronic lesions observed in liver (mononuclear cell infiltrates, necrosis, vacuolar hepatocytes, portal fibrosis, bile duct hyperplasia, active melanomacrophage centers) and gills (fusion and edema of secondary lamellae, laminar telangiectasis, mononuclear cell infiltrates, blebs) were similar to those in the literature studies for both wild and laboratory exposed sculpins and other fish species carrying similar or higher Hg concentrations. Ignoring sex and size, specimens with hepatic cell infiltrates had the highest concentrations of most elements, a relation that was also found for gill telangiectasis and Hg (all p<0.05). When controlling for sex and size, the prevalence of vacuolar hepatocytes and endoparasites was significantly highest at the three most contaminated stations and similar differences were found for liver necrosis. We suggest that beside exposure to mining-related elements, other environmental factors, such as parasites, might be co-factors in the development of the observed liver and gill lesions. Therefore, sculpin liver and gill pathology are likely to be suitable health indicators when biomonitoring gradients of mining and other element related activity effects; while a larger study is required to fully evaluate the relationships. - Highlights: • Black Angel Pb–Zn mine in West Greenland has led to significant metal pollution. • Gill and liver morphology of common sculpins was evaluated as bioindicators. • Significant pathologies were found and were related to metal concentrations. • Sculpin pathology may be suitable health indicators for mining activity effects. • These should be enrolled in EIAs of raw material industrialization in the Arctic.

54 ENVIRONMENTAL SCIENCES↗

Is Routine Splenectomy Justified for All Left-Sided Pancreatic Cancers? Histological Reappraisal of Splenic Hilar Lymphadenectomy

Background: Although splenectomy is recommended during resection for left-sided resectable pancreatic ductal adenocarcinoma (PDAC) to perform lymphadenectomy of station 10 (splenic hilum), no level I evidence justifies this procedure. This study aims to evaluate the rate of lymph node (LN) and contiguous involvement of the splenic hilum in resectable distal PDAC. Methods: We retrospectively reviewed all patients who underwent splenopancreatectomy for PDAC in the past 10 years. Station 10 LN were routinely isolated, and all corresponding microscopic slides were reinterpreted by a pathologist. The computed tomography (CT) results of patients with tumoral involvement of the spleen or splenic hilum by contiguity (TISOSH) and ≤ 10 mm between the tumor and spleen on pathology were blindly reviewed by two radiologists to evaluate CT for diagnosis of TISOSH. Results: We included 110 consecutive patients, including 104 with analyzable station 10 LN. The tumor was N+ in 58 (53%) patients. The median number of LN identified at station 10 was 2.0 ± 3.0. No station 10 LNs were detected in 42 (40%) patients. No patients had tumor-positive LN at station 10. TISOSH was found in nine (8%) patients, and was significantly associated with tail location (p = 0.001), tumor size (p = 0.005), and multivisceral involvement (p = 0.015). For diagnosis of TISOSH, the sensitivity and specificity of CT were respectively 89% and 95% for radiologist 1 and 89% and 100% for radiologist 2. Conclusions: Splenic preservation during resection of distal PDAC may be an option in selected patients with body tumors and no suspected splenic or splenic hilum involvement on preoperative CT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Microbiological and experimental-histological investigations of lunar samples returned by the Lunar 16 automatic station

Lunar surface material was studied for its content of viable microorganisms (aerobic and anaerobic, fungi, and viruses); the effect of the lunar surface material on the growth of microorganisms and its interaction with somatic cells of mammals was also observed. No viable microorganisms were detected; the samples exhibited neither stimulant or inhibitory action on the growth of microorganisms, and also showed no cytopathogenic action on tissue cultures. A suspension of lunar surface material particles was not toxic when parenterally administered to certain laboratory animals. The particles were subjected to intense phagocytosis by connective tissue cells in vivo and in vitro.

Kaulen, D. R.↗