Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT

This study aimed to evaluate the clinical use of choline-PET/CT for discriminating viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and evaluating the response of bone metastasis to treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Thirty patients with mCRPC underwent a total of 56 ¹¹C-choline-PET/CT scans for restaging, because 4 patients received 1 scan and 26 had 2 scans. Using 2 (pre- and post-treatment) ¹¹C-choline-PET/CT examinations per patient, treatment response was assessed according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 20 situations, in which only bony metastases were observed on ¹¹C-choline-PET/CT scans. Viable bone metastases and osteoblastic change induced by the treatment effect were identified in 53 (94.6%) and 29 (51.8%) of 56 ¹¹C-choline-PET/CT scans, respectively. In 27 cases (48.2%), ¹¹C-choline-PET/CT scans could discriminate the 2 entities. The mean SUVmax of the metastatic bony lesions was 5.82 ± 3.21, 5.95 ± 3.96, 6.73 ± 5.04, and 7.91 ± 3.25 for the osteoblastic, osteolytic, mixed, and invisible types, respectively. Of the 20 situations analyzed, CMR, PMR, SMD, and PMD, as determined by the EORTC, were seen in 1, 2, 3, and 14 cases, respectively. Of the 13 patients with increasing PSA trend, all 13 showed PMD. Of the 2 patients with PSA response of <50%, both 2 showed SMD. Of the 5 patients with PSA response of ≥50%, 1 showed CMR, 2 showed PMR, 1 showed SMD, and 1 showed PMD. Choline-PET/CT is very useful to discriminate viable progressive osteoblastic bone metastasis from osteoblastic change, and assess treatment response of bone metastases in mCRPC.     

Four types of Ipsilateral Breast Tumor Recurrence (IBTR) after breast‐conserving surgery: Classification of IBTR based on precise pathological examination

We classified ipsilateral breast tumor recurrences (IBTRs) based on strict pathological rules. Ninety‐six women who were surgically treated for IBTR were included. IBTRs were classified according to their origins and were distinguished based on strict pathological rules: relationship between the IBTR and the primary lumpectomy scar, surgical margin status of the primary cancer, and the presence of in situ lesions of IBTR. The prognosis of these subgroups were compared to that of new primary tumors (NP) in the narrow sense (NPn) that occurred far from the scar. Distant‐disease free survival of IBTR that occurred close to the scar with in situ lesions and a negative surgical margin of the primary cancer (NP occurred close to the scar, NPcs) was similar to that of NPn. In contrast, IBTR that occurred close to the scar without in situ lesions (true recurrence (TR) that arose from residual invasive carcinoma foci, TRinv) had significantly poorer prognosis than NPn. IBTR that occurred close to the scar with in situ lesions and a positive surgical margin of the primary cancer (TR arising from a residual in situ lesion, TRis) had more late recurrences than NPcs. Precise pathological examinations indicated four distinct IBTR subtypes with different characteristics.     

苦黄注射液联合复方蛋氨酸胆碱治疗酒精性脂肪肝的疗效及对肝纤维化的影响研究

目的 探究复方蛋氨酸胆碱结合苦黄注射液在酒精性脂肪肝治疗中的疗效及对肝纤维化的影响。方法 按照随机数字表法将2019年1月至2021年12月海安市人民医院收治并确诊的104例酒精性脂肪肝患者分为对照组和观察组,各52例。对照组给予复方蛋氨酸胆碱治疗,观察组苦黄注射液联合复方蛋氨酸胆碱治疗。两组患者均连续治疗1个月。采用全自动生化分析仪检测两组患者治疗前后血清丙氨酸转移酶（alanine transferase,ALT）、天冬氨酸转氨酶（aspartate aminotransferase,AST）、总胆固醇（total cholesterol ,TC）、三酰甘油（triacylglycerol,TG）、总胆红素（total bilirubin,TBil）水平;采用放射免疫法检测两组患者治疗前后血清层粘连蛋白（laminin,LN）、透明质酸（hyaluronic acid,HA）、Ⅲ型前胶原N端肽（type III procollagen N-terminal peptide,PC Ⅲ）及Ⅳ型胶原（type IV collagen,Ⅳ-C）水平。比较两组患者的临床症状改善情况、临床疗效、肝功能指标及肝纤维化指标。结果 观察组治疗后的腹胀、肝区不适、黄疸、痞满等症状消失时间分别为（3.9±0.1） d、（9.8±0.2） d、（11.5±0.7）d、（3.8±0.2） d,均短于对照组分别为（7.5±0.3） d、（14.3±0.4） d、（15.6±0.8） d、（7.4±0.3） d（均P<0.05）。观察组临床总有效率高于对照组（94.2% vs 78.9%）（χ2=5.283,P=0.022）。观察组ALT、AST、TC、TG、TBil水平分别为（31.5±5.3） IU/L、（36.4±3.4） IU/L、（4.1±0.2） mmol/L、（1.4±0.3） mmol/L、（12.6±3.1） μmol/L,低于对照组[分别为（57.4±5.6） IU/L、（54.7±3.5） IU/L、（6.4±0.4） mmol/L、（2.6±0.5） mmol/L、（21.2±5.3） μmol/L]（均P<0.05）。观察组治疗后LN、HA、PC Ⅲ、Ⅳ-C水平分别为（51.6±9.4） μg/L、（32.5±7.4） μg/L、（7.5±1.8） ng/mL、（32.3±4.2） μg/L,均低于对照组[分别为（80.5±10.3） μg/L、（58.7±12.2） μg/L、（16.5±3.6） ng/mL、（71.2±8.6） μg/L]（均P<0.05）。对照组和观察组不良反应发生率分别为7.68%、3.84%,两组比较无明显差异（χ2=0.707,P=0.400）。结论 复方蛋氨酸胆碱结合苦黄注射液在酒精性脂肪肝患者中的治疗疗效显著,可改善患者的临床症状和肝功能,延缓肝纤维化的进程,安全性高。     

Does steatohepatitis impair liver regeneration? A study in a dietary model of non-alcoholic steatohepatitis in rats

BACKGROUND: Impaired liver regeneration is a feature of alcoholic hepatitis, but the relative importance of alcohol, nutritional imbalance and inflammatory mediators in causing this effect is unclear. Non-alcoholic steatohepatitis (NASH) is a form of liver disease with similar morphology to alcoholic hepatitis, but the effect of this disorder on liver regeneration is unclear. We, therefore, examined the status of liver regeneration in a rat nutritional model of hepatic steatosis with inflammation, which is morphologically identical to NASH in humans. Methods: Male Wistar rats received a methionine-choline-deficient diet (MCDD) for 4 weeks before experiments and both isocaloric pair-fed and ad libitum-fed rats were used as controls. Following partial hepatectomy (68%), the extent of hepatic regeneration was determined 24 h later using [3H]-thymidine incorporation and restitution of liver mass. Results: There was no significant difference of [3H]-thymidine incorporation in MCDD-fed, pair-fed and ad libitum-fed rats (80+/-27, 78+/-11 and 80+/-6.3 d.p.m./microg DNA, respectively). Similarly, restituted liver masses in three groups of rats were not significantly different (17+/-3.8, 18+/-1.8 and 17+/-3.1% initial liver weight, respectively). Conclusions: The similarities in hepatic histology and cytochrome P450 2E1 induction between this nutritional model of hepatic steatohepatitis and alcoholic steatohepatitis imply that these two disorders share pathogenetic mechanisms. However, liver regeneration is not altered by NASH in rats, indicating that the nutritional and inflammatory changes that appear similar to those of alcoholic liver disease do not cause impairment of liver regeneration.     

Distinct Localization of Peripheral and Central Types of Choline Acetyltransferase in the Rat Cochlea

We previously discovered a splice variant of choline acetyltransferase (ChAT) mRNA, and designated the variant protein pChAT because of its preferential expression in peripheral neuronal structures. In this study, we examined the immunohistochemical localization of pChAT in rat cochlea and compared the distribution pattern to those of common ChAT (cChAT) and acetylcholinesterase. Some neuronal cell bodies and fibers in the spiral ganglia showed immunoreactivity for pChAT, predominantly the small spiral ganglion cells, indicating outer hair cell type II neurons. In contrast, cChAT- and acetylcholinesterase-positive structures were localized to fibers and not apparent in ganglion cells. After ablation of the cochlear nuclei, many pChAT-positive cochlear nerve fibers became clearly visible, whereas fibers immunopositive for cChAT and acetylcholine esterase disappeared. These results suggested that pChAT and cChAT are localized in different systems of the rat cochlea; pChAT in the afferent and cChAT in the efferent structures.     

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart

Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end-nets and flower-spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double-labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high-resolution maps of the rat subendocardial neural plexus at the cavo-atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo-atrial junction than the mid-atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post-ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower-spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.     

Radioactive choline metabolism in guinea pig gallbladder

Acetylcholine may be released from gallbladder intrinsic nerves in response to cholecystokinin stimulation. This study characterized metabolites of [¹⁴C]choline produced in the gallbladder and released during incubation, with or without cholecystokinin-octapeptide. Radiolabeled [¹⁴C]choline was applied to the mucosal or muscle surface of intact guinea pig gallbladders in an organ bath. After radiolabeling, gallbladders were incubated with or without the contractile agonist cholecystokinin-octapeptide. Metabolites of [¹⁴C]choline were identified in gallbladder tissue and incubation buffers using HPLC and thin-layer chromatography. The major metabolites of [¹⁴C]choline were betaine and phosphocholine. [¹⁴C]Phosphocholine was incorporated slowly into [¹⁴C]phosphatidylcholine. [¹⁴C]Choline was released into buffers during incubation. [¹⁴C]Acetylcholine constituted less than 1% of radiolabel in the gallbladder. There was no identifiable [¹⁴C]acetylcholine released in buffers. Cholecystokinin-octapeptide did not affect choline metabolism. These studies showed that choline in the gallbladder is metabolized along pathways similar to those in the liver. Gallbladders released mostly choline, rather than acetylcholine, even during hormonally induced contraction.This project was supported by the Research and Development Office of the Department of Veterans Affairs.