内源性一氧化碳对感染性休克大鼠器官保护作用及机制研究

目的探讨内源性一氧化碳（CO）对感染性休克大鼠肺、肝组织的保护作用及其机制。方法采用盲肠结扎穿孔术（CLP）复制感染性休克模型，按随机数字表法将96只大鼠分为假手术对照组、CLP组、CLP＋氯血红素（Hm）组和CLP＋锌原卟啉（ZnPP）组。各组分别在制模后2、4和6h测定出入肺血中碳氧血红蛋白（COHb）水平；肺、肝组织及血液中丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性；光镜下观察肺、肝组织形态学改变；免疫组化分析血红素加氧酶-1（HO-1）在肺、肝组织中的蛋白表达和分布。结果与假手术对照组比较，CLP组大鼠不同时间点的出入肺血中COHb水平以及肺、肝组织和全血中MDA含量均显著增高（P〈0．05或P〈0．01），SOD活性显著下降（P〈0．05或P〈0．01）；光镜下肺、肝组织损伤严重，HO-1蛋白表达增多。给予Hm后不同时间点，出、入肺血中的COHb水平均较CLP组进一步升高，肺、肝组织及全血中MDA含量均显著下降，SOD活性显著增高；光镜下肺、肝组织损伤明显缓解，HO-1蛋白表达进一步增多。结论感染性休克时内源性CO产生增多可能对肺、肝组织发挥了保护作用。     

尿路感染患者病原菌分布特征、免疫功能及相关因子水平检测

目的分析尿路感染患者病原菌分布特征、免疫功能、血红素加氧酶-1(HO-1)及降钙素原(PCT)水平的变化。方法收集2016年8月至2018年8月于咸宁市中心医院就诊的尿路感染患者200例为观察组,收集同期来该院体检的健康志愿者200例为对照组。分析观察组患者病原菌分布情况;检测并比较两组研究对象免疫球蛋白(Ig)A、IgM、IgG、HO-1及PCT水平。结果观察组患者尿液标本共检测出病原微生物158株,其中革兰阴性菌109株(68.99%),以大肠埃希菌76株(48.10%)为主;革兰阳性菌41株(25.95%),以屎肠球菌25株(15.82%)为主;真菌8株(5.06%)。观察组患者血清中IgA、IgM、IgG水平明显低于对照组,血清HO-1、PCT水平均明显高于对照组(P0.05)。结论尿路感染患者病原菌分布广泛,以革兰阴性菌为主。尿路感染可导致患者出现免疫功能下降及炎症状态,临床治疗时应加强对上述指标的检测及干预。     

甲状腺素对大鼠肝脏缺血再灌注后血红素加氧酶-1表达的影响

目的 探讨甲状腺素对大鼠肝脏缺血再灌注后血红素加氧酶-1(HO-1)表达的影响及其对肝脏的保护作用与机制.方法 建立70%大鼠肝脏缺血再灌注损伤模型(缺血1 h,再灌注6 h),将30 只雄性Sprague-Dawley 大鼠随机分为假手术组、对照组、处理组三组,每组10 只.处理方法为于缺血48 h 前0.1 mg/kg 的T3 腹腔注射.测定再灌注末血清ALT、AST 和肝脏组织丙二醛(MDA)、超氧化物歧化酶(SOD)的变化,HE 染色光镜下肝组织学观察.应用Western blot 及RT-PCR检测肝脏HO-1 的表达.结果 与假手术组相比,对照组细胞上清液中ALT、AST 和MDA 含量明显较高(P ＜0.05),SOD 明显较低(P ＜0.05);肝细胞坏死严重,排列紊乱.处理组的ALT、AST 和MDA 显著低于对照组(P ＜0.05),SOD 明显高于对照组(P ＜0.05);肝细胞坏死减轻,排列相对整齐.假手术组有少量HO-1 表达,处理组HO-1 表达高于对照组,差异有统计学意义(P ＜0.05).结论 甲状腺素能上调HO-1 的表达以减少肝细胞坏死,减轻大鼠肝脏缺血再灌注损伤,从而对肝脏有保护作用.     

血红素氧合酶1在百草枯中毒肾脏中的表达及褪黑素对其的影响

目的观察百草枯中毒大鼠肾组织中血红素氧合酶-1（HO-1）的表达,探讨其病理生理机制。方法 SD大鼠126只随机分为空白对照组、中毒组和褪黑素组,各42只。中毒组、褪黑素组予以百草枯（25mg/kg）腹腔注射染毒,对照组予以等量生理盐水腹腔注射,15min后褪黑素组予以褪黑素（10mg/kg）腹腔注射,对照组、中毒组予以等量生理盐水腹腔注射。于1、3、6、12h,1、2、3、5d时各组随机取6只处死。苏木精伊红（HE）染色观察各组肾组织病理学变化,采用免疫组识化学和RT-PCR观察肾组织HO-1蛋白和mRNA表达。结果①与对照组相比,中毒组染毒后3h即可见充血、水肿及空泡变性等病理变化,1d达顶峰,病理损伤评分3.30±0.31（P〈0.05）,其后缓解趋势不明显;而褪黑素组病理变化明显减轻且缓解趋势明显,1d时病理损伤评分2.70±0.26,与中毒组相比差异有统计学意义（P〈0.05）。②与对照组相比,中毒组染毒3h在皮质部肾小管上皮细胞的细胞膜及细胞浆HO-1呈阳性表达,免疫组识化学评分（IHS）3.33±1.75,HO-1mRNA表达增强,与对照组相比差异有统计学意义（P〈0.05）,1d达顶峰,HIS为7.00±2.00,之后减弱,5d仍有阳性表达,但与对照组相比差异无统计学意义（P〉0.05）;褪黑素组HO-1表达较中毒组明显增强,IHS评分6h～3d差异具有统计学意义（P〈0.05）,5d不再有统计学意义（P〉0.05）。结论 HO-1在百草枯中毒大鼠肾组织中呈高表达,褪黑素能明显改善百草枯中毒肾脏病理损伤,增强HO-1表达可能是其作用途径之一,而氧化损伤可能是百草枯中毒肾损伤病理生理机制之一。     

血红素加氧酶1在呼吸系统疾病中的研究进展

血红素加氧酶（heme oxygenase,HO）及其同工酶自20世纪80年代中末期获得分离纯化后,迄今为止发现有HO-1、HO-2、HO-3三种同工酶。     

血红素加氧酶-1在食管癌中的表达及意义

目的:血红素加氧酶-1(heme oxygenase,HO-1)在多种实体肿瘤中高表达,与恶性肿瘤发生、浸润和转移密切相关.本研究旨在研究HO-1在食管癌中的表达及意义.方法:76例食管癌石蜡标本制成组织芯片,以28例癌旁组织、65例正常食管组织为对照,均采用Envision两步法进行免疫组化检测.结果:HO-1在食管组织细胞核、细胞浆及细胞膜中均有表达,正常组织中以细胞核表达为主,食管癌组织中以细胞浆/膜表达为主.在细胞核的表达上,癌组织、癌旁组织及正常组织差异无显著性(P>0.05);在细胞浆及细胞膜表达上,食管癌中的阳性表达率显著高于在癌旁组织和正常食管组织的表达率(P<0.05),其表达水平与淋巴结转移、癌组织浸润程度及组织分化程度相关(P<0.05),与患者性别、年龄、肿块大小、部位等差异无显著性(P>0.05).结论:HO-1在食管癌的细胞浆/膜上具有较高的差异性表达.且与淋巴结转移密切相关,提示食管癌的发生、侵袭和转移可能与HO-1相关,HO-1有可能作为食管癌新的标志物以及评估食管癌进展的客观指标.     

血清HO-1、NBNA评分在早产儿脑损伤中变化分析及对脑发育预后评估的价值

目的 探讨血清血红素加氧酶-1(HO-1)、新生儿神经行为测定(NBNA)评分在早产儿脑损伤中的变化情况,并分析二者对脑发育预后评估的价值。方法 纳入2017年9月至2020年4月于该院产科分娩的早产儿130例,根据有无脑损伤分成脑损伤组(n=52)、对照组(n=78),并按照脑损伤组的胎龄分成胎龄<32周(A组,n=16)、胎龄32～<34周(B组,n=19)、胎龄34～36周(C组,n=17)。比较脑损伤组、对照组出生后第3、7、14天的血清HO-1水平与NBNA评分,并分析不同胎龄脑损伤患儿的血清HO-1水平与NBNA评分变化。在脑损伤患儿矫正胎龄至40周后随访6个月,经振幅整合脑电图(aEEG)评估脑发育情况,并分成良好组(n=39)、不良组(n=13),绘制受试者工作特征曲线(ROC)分析血清HO-1、NBNA评分对脑发育预后的评估价值。结果 脑损伤组第3、7、14天的血清HO-1水平及均值高于对照组,而NBNA评分及均值低于对照组,差异有统计学意义(P<0.05)。A组第3、7、14天的血清HO-1水平及均值高于B、C组,且B组高于C组,而A组第3、7、1...     

血红素氧化酶-1在肺纤维化中的作用研究进展

肺纤维化是一类发展快、死亡率高的疾病,目前肺纤维化的治疗方案非常有限。血红素氧化酶-1(HO-1)作为一种氧化应激反应蛋白,近年来人们发现其在肺纤维化中发挥着许多重要作用,包括抗氧化应激、抗凋亡和抗炎。为了更好理解HO-1和肺纤维化之间的关系,本文回顾了最近的研究,试图为肺纤维化的治疗提供一个全新的靶点。     

血红素加氧酶-1对糖尿病大鼠神经病理性疼痛的影响及可能的机制

目的:通过抑制和诱导血红素加氧酶-1(HO-1)的表达,探讨其对糖尿病大鼠神经病理性疼痛的影响及可能的机制。方法:将造模成功的24只糖尿病大鼠随机分为3组(n=8):糖尿病组(A组);糖尿病+锌原卟啉干预组(B组);糖尿病+钴原卟啉干预组(C组)。另取8只大鼠作为正常对照(D组)。于造模前及造模后不同时点测大鼠的机械性缩足反应阈值(paw withdrawalmechanical threshold,PWMT)。造模后43 d麻醉大鼠,取坐骨神经制成电镜标本;取L4~L6段脊髓,行HE染色、免疫组化染色及原位末端标记(TUNEL)检测。结果:与造模前相比,A、B、C组造模后7~42 d的PWMT显著降低(P<0.01)。造模后14~42 d,与A组比,C组PWMT显著升高(P<0.05),而B组则显著降低(P<0.05)。C组脊髓背角神经元及坐骨神经病变的程度较A组减轻;而B组则较A组加重。与A组比,C组脊髓背角神经元胞浆中HO-1表达增强,凋亡发生率显著降低(P<0.01);而B组HO-1表达减弱,凋亡发生率显著升高(P<0.01)。结论:HO-1对糖尿病神经病理性疼痛有治疗作用,这可能与其能够减轻糖尿病外周神经病变及抑制脊髓背角神经元凋亡有关。     

恶性肿瘤合并高钙血症23例临床特点及预后分析

目的分析恶性肿瘤伴高钙血症患者的临床诊治特点以及预后情况。方法回顾性分析焦作市第二人民医院肿瘤内科2004-01-2009-06收治的23例晚期恶性肿瘤合并高钙血症患者的临床资料,并随访观察其生存情况,分析其临床特点、诊治规律及影响预后的主要因素。结果 22例患者血钙浓度为2.78~4.37 mmol/L,经双膦酸盐治疗后血钙均降至正常;发现高钙血症后生存时间为3~153 d,中位生存时间仅为36 d。结论高钙血症多见于恶性肿瘤晚期,预后差,应早期诊断,积极予双膦酸盐类药物降血钙治疗。     

The management of hypercalcemia of malignancy

Hypercalcemia (HCM) occurs in 10–15% of all malignancies, predominantly in patients with solid tumors. This metabolic complication leads to significant morbidity and impairment of quality of life. Recent insights into the pathophysiology of HCM include an understanding of the role of parathyroid-hormone-related peptide and several cytokines secreted by tumors. The osteoclast plays a central role as the final common pathway through which these hormones and cytokines act to cause bone lysis. These findings have led to the development of new treatment strategies. Foremost among these has been the introduction of agents such as the newer bisphosphonates and gallium nitrate, which are potent inhibitors of osteoclast-mediated bone resorption. The clinician can now choose from an array of therapeutic approaches based on a consideration of the mechanisms of action, individual clinical circumstances, efficacy, toxicities and costs of available agents. In addition to their use in the management of HCM, non-toxic drugs that effectively inhibit osteoclast function, such as the bisphosphonates, are playing an emerging role in the palliative treatment of the more common clinical problems of painful lytic bone metastases and osteoporosis.Presented as an invited lecture at the 6th International Symposium: Supportive Care in Cancer, New Orleans, La., USA, 2–5 March 1994     

Parathyroid hormone-related protein, parathyroid hormone, and vitamin D in hypercalcemia of malignancy

The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. In the majority of cancer patients, hypercalcemia appears to be a consequence of the tumor production of parathyroid hormone (PTH)-related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy, in contrast to those with primary hyperparathyroidism, have an uncoupled bone turnover, and they usually have low circulating levels of 1,25(OH)₂D₃. We performed a case-control study to assess the relationship of plasma PTHrP, PTH and 1,25(OH)₂D₃ with hypercalcemia in cancer patients with a variety of tumors. Sixty of these patients had hypercalcemia, and 45 were normocalcemic. We measured PTHrP and PTH by immunoradiometric assay (Nichols), and 1,25(OH)₂D₃ by radioreceptor assay (Nichols), in plasma in both groups of cancer patients. Using a logistic regression analysis, we found that the higher PTHrP in plasma, the higher association with hypercalcemia occurred in these patients. In addition, the decreased plasma levels of PTH and 1,25(OH)₂D₃ in the majority of cancer patients were found to be significantly associated with hypercalcemia. Our results indicate that the combined determination of PTH, PTHrP and 1,25(OH)₂D₃ in plasma represents a more comprehensive approach to the investigation of hypercalcemia in cancer patients. Our data also support the role of PTHrP as a humoral factor responsible for hypercalcemia in these patients.     

18F-FDG PET/CT参数联合临床特征预测手术治疗早期宫颈癌患者预后

目的探讨¹⁸F-FDG PET/CT参数联合临床特征对预测早期宫颈癌患者手术治疗后预后的价值。方法回顾性分析70例术前接受¹⁸F-FDG PET/CT检查的早期宫颈癌患者,比较术后复发组与无复发组间代谢参数的差异,评价¹⁸F-FDG PET/CT参数结合临床特征对预后的预测价值。结果术后平均随访(53.86±15.74)个月,期间11例(11/70,15.71%)肿瘤复发。相关¹⁸F-FDG PET/CT参数中,峰值标准摄取值(SUV_peak)可预测肿瘤复发(AUC=0.672,P=0.03)。多因素比例风险模型(Cox)显示,淋巴结转移状态及SUV_peak是最主要的预测因素。结论 SUV_peak和淋巴结转移状态是评价手术治疗后早期宫颈癌患者预后的主要指标。     

基于临床联合CT影像组学特征列线图预测急性胰腺炎预后

目的 观察基于临床联合CT影像组学特征构建的联合模型列线图预测急性胰腺炎(AP)预后的价值。方法 回顾性分析203例临床首诊AP患者的临床及上腹部CT资料,按7∶3比例将其分为训练集(n=142)和验证集(n=61),基于增强静脉期CT提取并筛选最优影像组学特征,计算影像组学评分Radscore;根据预后分为预后良好组(n=114)与预后不良组(n=89)。将临床变量(包括临床及CT表现)及Radscore纳入单因素和多因素逻辑回归分析,筛选影响AP预后的独立危险因素;构建临床、影像组学和联合模型,以受试者工作特征(ROC)曲线评价其预测AP预后的效能;以联合模型预测指标构建列线图,结合校准曲线评估其校准度。结果 共筛选出7个最优影像组学特征用于计算Radscore,其中C反应蛋白、糖尿病史和Radscore为影响AP预后的独立危险因素。联合模型预测训练集及验证集AP预后的AUC(0.84、0.82)均高于临床模型(0.71、0.66,Z=3.12、2.71,P均<0.05);其预测训练集的AUC(0.84)高于影像组学模型(0.76,Z=2.39,P=0.02),预测验证集的A...     

老年高钙血症3例并文献复习

目的 分析老年高钙血症患者的临床特点及原因。方法 回顾性分析陕西省人民医院收治的3例老年高钙血症患者的临床表现及诊治经过,并对相关文献进行复习。结果 3例老年高钙血症患者临床表现各异,其中以嗜睡为首发症状1例,全身肌无力症状1例,言语障碍1例。3例均行多项检查,最后查血清钙,确诊高钙血症,给予大量补液、利尿、鲑鱼降钙素肌肉注射、床旁血液滤过等治疗措施后,血清钙水平明显下降,临床症状改善。结论 当老年人突发意识改变、全身肌无力、言语障碍时,应警惕高钙血症的可能性,及时测定血清钙离子。由于老年患者高钙血症的发病常常较为隐匿,且临床症状无特异性,在排除了心脑血管疾病急性发作且疗效不理想时,要拓展诊疗思路,注意排除高钙血症的可能性。     

Low HDL levels and the risk of death,sepsis and malignancy

Background High density lipoprotein (HDL) plays an important role as an anti-atherogenic molecule, but also possesses anti-inflammatory and anti-angiogenic properties. The effect of extremely low levels of HDL on the risk of sepsis and malignancy were therefore examined. Methods A retrospective analysis of patients hospitalized at the Edith Wolfson Medical center was conducted. Patients were divided into Group 1: 108 patients with serum HDL levels ≤20 mg/dl. Group 2: 96 patients with serum HDL levels ≥65 mg/dl. Medical history and laboratory data was recorded. Results The mean HDL levels in Group 1 were 16.1 ± 33 mg/dl compared to 74.9 ± 12.6 mg/dl in Group 2. Using a multivariate logistic regression analysis, low HDL was inversely associated with death (OR 0.96, 95% 0.93–0.99, P = 0.02), 3.98 fold increase in odds of fever (OR 3.98, 95% CI 1.3–11.8, P = 0.01), and 6.7-fold increase in the risk of cancer (OR 6.68, 95% CI 1.8–24.5, P = 0.004). HDL serum levels were inversely associated with sepsis. For each 1 mg/dl increase in HDL, a relative 11% decrease in odds of sepsis was observed (OR 0.886, 95% CI 0.8–0.976, P = 0.01). Conclusions Extremely low serum HDL levels (≤20 mg/dl) are associated with an increased risk of death, sepsis and malignancy.     

探讨急性淋巴细胞白血病患者费城染色体阳性的生物学特征及临床预后

目的分析费城(Ph)染色体阳性(+)急性淋巴细胞白血病(ALL)的发生率,探讨其生物学特征与临床预后的关系。方法应用G显带的常规细胞遗传学技术对300例ALL患者进行检测,其中Ph染色体(+)患者36例,Ph染色体阴性(-)患者264例,分析Ph染色体(+)组患者与Ph染色体(-)组患者的生物学特征、缓解率、生存期差异。结果 300例ALL初诊患者发现Ph染色体(+)患者36例,Ph染色体阳性率为12.0%。Ph(+)组患者的中位血红蛋白、血小板计数、外周血和骨髓幼稚淋巴细胞比例与Ph染色体(-)组患者比较,差异均无统计学意义(P0.05);但Ph(+)组患者的白细胞计数明显高于Ph(-)组患者,差异有统计学意义(P0.05)。36例Ph染色体(+)患者免疫分型资料显示:前B-ALL 9例、My+-ALL 5例、Common-ALL 22例。预后分析显示:Ph(+)组ALL患者和Ph(-)组ALL患者的第1次缓解率分别为52.8%(19/36)和84.8%(224/264),两组比较,差异有统计学意义(χ2=29.89,P0.05);两组复发率分别为57.9%(11/19)和25.4%(57/224),两组比较,差异有统计学意义(χ2=22.13,P0.05)。两组患者随访期内中位生存期分别为8、34个月。结论 Ph染色体(+)ALL患者比Ph染色体(-)ALL患者预后更差,生存期短,临床上要注意根据Ph染色体阳性与否采取相应的治疗策略。     

年轻宫颈癌患者临床特征及预后Meta分析

目的探讨年龄≤35岁年轻宫颈癌患者发病的临床病理特点。方法检索Pubmed、Ovid-medline全文数据库、CNKI、维普数据库、万方数据库等并收集有关年龄≤35岁年轻宫颈癌患者与>35岁的中老年宫颈癌患者的病例对照研究文献,按预定标准进行筛选,对纳入研究进行质量评价,并提取相应指标完成Meta分析。结果根据本研究的纳入与排除标准,最终纳入文献16篇,其中英文文献3篇,中文文献13篇,共包括13 714例宫颈癌患者(年轻宫颈癌患者2 582例,中老年宫颈癌患者11 132例)。Meta分析表明:年轻宫颈癌患者临床分期为早期(0^ⅡA)发生率、病理组织学分型为宫颈非鳞癌(腺癌为主)发生率、组织学分级为低分化(G3)、盆腔淋巴结转移阳性发生率显著高于中老年宫颈癌患者。癌灶直径大于4 cm、宫颈基层浸润深度≥1/2、脉管浸润的差异无统计学意义。结论 35岁以下年轻宫颈癌患者临床分期以早期癌为主,病理组织学分型为低分化非鳞癌,但生存率较中老年组低。应加强宫颈癌防治知识的宣传和筛查的推广,做到早诊断、早治疗。     

基于CT增强图像纹理特征预测可切除胃癌患者预后

目的 探讨基于术前CT增强图像纹理特征预测可切除胃癌患者预后的价值。方法 回顾性分析197例经手术病理确诊胃癌患者，随机分为训练组（n=147）和验证组（n=50）。于术前CT增强门静脉期图像中提取90个病灶三维定量特征，采用组间相关系数（ICC）从中选择可重复性好者，以LASSO COX回归模型进行降维并筛选出与患者总生存时间（OS）相关特征，建立影像标签，对2组患者进行分类，根据标签分数的中位数值分为高危组和低危组，观察组间OS差异，分析临床、病理特征及影像纹理特征标签与患者预后的关系。构建融合纹理特征标签和临床病理特征的诺莫图，评价其预测胃癌患者预后的效能；绘制决策曲线，评价其临床价值。结果 经筛选获得2个与患者OS相关的CT纹理特征并以之建立影像标签。训练组（χ²=9.25）和验证组（χ²=8.49）中，高危组和低危组患者OS差异均有统计学意义（P均<0.01）。影像标签及TNM分期为胃癌的独立危险因素。影像标签预测训练组和验证组患者3年OS的AUC分别为0.72（P=0.02）和0.67（P=0.07），融合影像标签和TNM分期的诺莫图模型预测3年OS的AUC分别为0.78和0.81（P均<0.01）。阈值为0.13~0.59时，诺莫图模型的净获益高于单独影像标签。结论 基于CT增强图像纹理特征建立的影像标签可用于胃癌患者术后危险分层；联合病理特征构建的纹理诺模图模型有助于预测患者预后。     

Evaluation of the risk factors for febrile neutropenia associated with hematological malignancy

Febrile neutropenia (FN) can frequently become a very serious problem. In 2002, Klastersky and colleagues established the Multinational Association for Supportive Care in Cancer (MASCC) score, which consisted of risk factors for conditions that included solid tumors. However, hematopoietic tumors, in comparison to solid tumors, are plagued by such problems as the quantity and quality of abnormalities associated with leukocytes and neutrophils and the requirement for higher dosages of both radio- and chemotherapy. FN is a complication associated with hematological malignancies that can lead to a fatal outcome, but it is avoidable if the appropriate preventive treatment is performed at an early stage. The subjects of the present study consisted of 354 patients with hematopoietic malignancies who were treated at the Japanese Red Cross Medical Center Hospital, Tokyo, between August 2000 and September 2004. They were retrospectively evaluated for the risk factors of FN by applying Wilcoxon’s rank sum test. A scoring index was defined and the patients were classified into high- and low-risk groups before evaluation. The following nine risk factors, which may significantly influence the relationship between the time required for defervescence and the duration of neutropenia — age; hematological diseases; the leukocyte count during the febrile period; the reduction in leukocyte count per day before the onset of FN; the prophylactic administration of antimycotic agents; sterilization of the intestinal tract; and urine albumin content, creatine level, and C-reactive protein (CRP) level — were expressed in points and their sum was termed risk points. The range of risk points was classified as 0–3 and 4–9. The time required for defervescence was 5.1 days when the risk points were in the range of 0–3 and 8.1 days when the points were in the range of 4–9. These figures were distributed normally and there was a significant difference between the two groups (P = 0.0016). FN associated with hematological malignancies is somewhat different from that related to other malignancies; it is therefore associated with unique risk factors. Most of the risk factors used in the present study can be evaluated objectively. At the onset of FN, they were expressed in points for evaluation. Further prospective studies are needed to determine whether these risk factors are suitable for use in actual cases.