^18F-FDG PET/CT对可疑复发性宫颈癌的临床价值

目的 探讨^18F-FDG PET/CT在可疑复发性宫颈癌临床诊疗中的价值.方法 回顾性分析51例宫颈癌根治后随访期间临床可疑复发的患者,记录患者的治疗资料、可疑复发表现、18F-FDG PET/CT显像结果、同期常规影像检查结果、病理及临床随访结果、PET/CT结果对临床诊疗的影响.结果 PET/CT诊断宫颈癌复发43例,最终经病理检查及临床随访证实复发性宫颈癌40例,盆腔脓肿2例,放射性肠炎1例;PET/CT未见恶性征象8例,病理检查及临床随访均未见异常.PET/CT诊断复发性宫颈癌灵敏度为100.00%（40/40）,特异性为72.73%（8/11）,准确性为94.12%（48/51）.PET/CT指导制订临床诊疗及随访计划34例,改变治疗计划7例.与其他影像检查相比,PET/CT可发现更多的病灶.结论^18F-FDG PET/CT能有效诊断复发性宫颈癌,指导临床诊疗.     

18F-FDG PET/CT显像在治疗后宫颈癌评估中的价值

目的 探讨18F-FDG PET/CT对临床怀疑宫颈癌局部复发和(或)远处转移患者的诊断价值.方法 回顾性分析95例宫颈癌治疗后患者的18F-FDG PET/CT检查资料,采用视觉分析和半定量方法(SUVmax)分析病灶特点,最终诊断以活组织病理检查、诊断性治疗及影像学随访结果为准,采用Kappa一致性检验进行分析.结果 共有54例患者18 F-FDG PET/CT检查发现局部复发和(或)远处转移病灶,其中局部复发24例,远处转移30例;18F-FDG PET/CT诊断肿瘤复发与转移的灵敏度、特异性和准确性分别为98.1％(52/53)、95.2％ (40/42)和96.8％ (92/95),阳性预测值与阴性预测值分别为96.3％ (52/54)和97.6％(40/41).18F-FDG PET/CT检查结果与病理及临床随访结果一致性良好(Kappa=0.936,P＜0.05).结论 18F-FDG PET/CT对临床可疑宫颈癌复发的诊断具有较高的灵敏度和特异性,有助于局部复发和(或)远处转移病灶的检测,对临床进一步的诊疗具有指导作用.     

18F-FDG PET/CT在黑色素瘤中的应用价值

目的 探讨18F-脱氧葡萄糖(FDG)PET/CT显像在黑色素瘤诊断、临床分期及监测治疗后肿瘤复发与转移灶中的应用价值.方法 黑色素瘤患者61例,均进行18F-FDG PET/CT全身显像.所有PET、CT及PET/CT融合图像均通过融合软件进行帧对帧对比分析.肿瘤病灶根据病理学检查、多种影像学检查及临床随访结果诊断.结果 18F-FDG PET/CT显像对黑色素瘤病灶检出的灵敏度、特异性和准确性分别为90.9%(40/44)、88.2%(15/17)和90.2%(55/61).其中12例治疗前患者中,18F-FDG PET/CT显像诊断的灵敏度为83.3%(10/12).在黑色素瘤病灶局部切除、尚未进行其他治疗的9例患者中,5例残余病灶18F-FDG PET/CT显像检出3例;4例远处转移灶患者全被检出,提高了临床分期,改变了治疗方案.首先发现转移性黑色素瘤病灶并且手术切除后,寻找原发灶的7例患者中,18F-FDG PET/CT检出原发灶2例,4例其他转移灶全被检出.黑色素瘤患者根治术后监测肿瘤复发或转移患者33例,18F-FDG PET/CT显像灵敏度、特异性和准确性分别为100.0%(19/19)、85.7%(12/14)和93.9%(31/33).与同期临床其他影像学检查比较,18F-FDG PET/CT显像发现更多,33例患者中,16例(48.5%)病灶提高临床分期;7例(21.2%)排除可疑病灶,降低临床分期;10例(30.3%)检出病灶与临床一致.结论 18F-FDG PET/CT显像对于黑色素瘤的诊断,残余病灶、复发病灶及转移灶的检出,临床分期的明确具有重要价值.     

18F-FDG PET/CT对可疑复发性宫颈癌的临床价值

目的 探讨18F-FDG PET/CT在可疑复发性宫颈癌临床诊疗中的价值.方法 回顾性分析51例宫颈癌根治后随访期间临床可疑复发的患者,记录患者的治疗资料、可疑复发表现、18F-FDG PET/CT显像结果、同期常规影像检查结果、病理及临床随访结果、PET/CT结果对临床诊疗的影响.结果 PET/CT诊断宫颈癌复发43例,最终经病理检查及临床随访证实复发性宫颈癌40例,盆腔脓肿2例,放射性肠炎1例;PET/CT未见恶性征象8例,病理检查及临床随访均未见异常.PET/CT诊断复发性宫颈癌灵敏度为100.00%(40/40),特异性为72.73%(8/11),准确性为94.12%(48/51).PET/CT指导制订临床诊疗及随访计划34例,改变治疗计划7例.与其他影像检查相比,PET/CT可发现更多的病灶.结论 18F-FDG PET/CT能有效诊断复发性宫颈癌,指导临床诊疗.     

18F-FDG PET/CT在Castleman病中的临床应用价值

目的 评价18F-FDG PET/CT在Castleman病(CD)的临床分型、疗效评价及转化监测中的应用价值.方法 回顾性分析14例CD患者[年龄(45.64±14.30)岁,男、女各7例]的18F-FDGPET/CT影像表现(病灶数量、分布、SUVmax),比较不同临床分型、病理类型、病理转化患者的影像表现,并对4例化疗后复查18 F-FDG PET/CT患者的病灶影像学变化进行记录.数据比较采用Mann-Whitney及Kruskal-Wallis秩和检验.结果 12例病理未发生转化的CD患者,化疗前18 F-FDG PET/CT检查均有1个或多个淋巴结肿大且伴有葡萄糖代谢增高,SUVmax3.94± 1.44(1.9 ～ 6.8);临床类型为单中心(2/12)与多中心(10/12) CD的SUV max分别为4.55±3.18和3.82±1.14,差异无统计学意义(Z=0.22,P＞0.05);病理类型分别为透明血管型(4/12)、浆细胞型(6/12)、混合型(2/12) CD的SUVmax分别为3.56±0.96、4.73± 1.41和2.30±0.57,差异无统计学意义(x2=4.74,P＞0.05).4例(4/12)化疗后复查PET/CT的患者中,3例病灶完全消失,1例病灶缩小、代谢减低.2例(2/14)发生病理转化的患者,SUVmax10.85±2.05,高于未转化者(3.94±1.44;Z=-2.19,P＜0.05).结论 18F-FDGPET/CT对于指导CD的临床分型、评价化疗疗效和监测病理转化均有一定的应用价值.     

18F-FDG PET/CT对肾脏肿瘤的诊断价值

目的 探讨18F-FDG PET/CT对肾脏肿瘤的临床诊断价值.方法 回顾性分析近5年经18 F-FDG PET/CT诊断为肾脏肿瘤且病理或临床综合诊断明确的79例患者资料,其中男52例,女27例,平均年龄(57.3±14.1)岁.PET/CT诊断根据肾脏轮廓改变、病灶密度异常及FDG摄取程度做出.计算18F-FDG PET/CT诊断肾脏肿瘤的效能指标.结果 79例中恶性肿瘤70例(包括肾细胞癌40例、肾盂癌5例,淋巴瘤8例,转移瘤16例,肾筋膜囊脂肪肉瘤1例);良性肿瘤9例(包括血管平滑肌脂肪瘤7例,肾嗜酸细胞腺瘤1例,后肾腺瘤1例;不含小脂滴样错构瘤病例).18 F-FDG PET/CT对病灶检出率达97.5％(77/79),对肾脏良恶性病灶判断的灵敏度为92.9％ (65/70),特异性为7/9,准确性为91.1％ (72/79),阳性预测值为97.0％(65/67),阴性预测值为58.3％ (7/12).结论 18 F-FDG PET/CT能够检出并判断大部分肾脏占位病变性质,对肾脏肿瘤患者进行全身检查并做出综合评价是18F-FDG PET/CT的优势之一.     

18F-FDG PET/CT在甲状腺癌中的临床应用

甲状腺癌是最常见的内分泌肿瘤,其显像方法很多,但由于甲状腺癌生物学行为的多重性,不同的显像方法对其的诊断价值及生物学行为判断价值各有不同.目前,18F-FDG PET/CT显像对不同进展期的甲状腺癌临床判断价值显著,其最重要的临床应用在于病灶诊断、分期和再分期及对各种治疗的评价和预后判断.笔者主要就18F-FDG PET/CT显像在甲状腺癌中的临床应用进行综述.     

18F-FDG PET/CT发现肿瘤患者意外病灶的临床价值

目的评价^18F-脱氧葡萄糖（FDG）PET／CT全身显像探测肿瘤患者意外病灶的临床价值。方法回顾性分析澳大利亚Peter MaeCallum肿瘤医院PET／CT中心2002年8月～2003年7月1727例肿瘤患者^18F—FDGPET／CT全身显像报告，男980例，女747例，中位年龄63岁，随访37个月（中位时间为27．5个月）。意外病灶指新发现的与原发肿瘤无关的良性病灶或第2原发肿瘤。通过分析病历记录、病理结果、其他影像学检查结果及临床随访，确定病灶最终结果。结果1727例患者共发现238例（13．8％）有意外病灶，其中213例220个意外病灶具有完整的随访资料。60个病灶怀疑为意外第2原发肿瘤，其中21．7％（13／60）证实为真阳性，70．0％（42／60）为假阳性，8．3％（5／60）至研究结束时未得到证实。38个甲状腺意外良性病灶，其中9个被证实为临床前恶性或恶性病灶，26个良性，3个未能证实。38个纵隔意外良性病灶，其中86．8％（33／38）证实为良性，7．9％（3／38）为原发肿瘤淋巴结侵犯，5．3％（2／38）未能证实其性质。其他部位84个意外良眭病灶，94．0％（79／84）证实为真阴性，6．0％（5／84）未能证实。共22例患者被证实存在第2原发肿瘤病灶，占本研究总人群的1．3％。结论^18F—FDGPET／CT全身显像是目前探测肿瘤患者意外病灶较好的无创方法，为制定临床治疗方案提供及时准确的依据。     

18F-FDG PET/CT显像鉴别腹腔积液性质的价值

目的 探讨18F-FDG PET/CT显像在不明原因腹腔积液患者积液性质鉴别诊断中的作用.方法 回顾性分析因不明原因腹腔积液入院的初诊患者70例,所有患者均行18F-FDG PET/CT 显像、同机CT平扫和腹腔积液细胞学检查,PET/CT显像计算病灶SUV.结果经组织病理学、腹腔镜、胃镜、肠镜等检查及临床随访确定,随访时间均大于6个月.对疑有胃肠道病变患者行PET/CT 延迟显像以明确诊断.有无腹膜转移组间SUVmax差异行两样本t检验;PET/CT、同机CT平扫及腹腔积液细胞学检查对腹膜转移诊断效能比较用McNemar检验;三者与最终结果吻合度检验用Kappa检验.结果 腹腔积液患者70例,经手术、腹膜活组织检查或腹腔积液细胞学检查证实48例为腹膜转移癌引起的恶性积液,22例为良性积液.2组腹膜的SUVmax分别为6.08±3.92和2.66±1.74,差异有统计学意义(t=-5.063,P＜0.001).PET/CT诊断45例为恶性积液,其中2例为假阳性,另有5例恶性积液被误诊为良性积液,PET/CT诊断腹膜转移的灵敏度、特异性和准确性分别为89.6％ (43/48)、90.9％ (20/22)和90.0％ (63/70).定位CT诊断27例为腹膜转移,其中4例为假阳性,CT 准确诊断良性腹腔积液18例,另有25例假阴性;定位CT诊断腹膜转移的灵敏度、特异性和准确性分别为47.9％ (23/48)、81.8％ (18/22)和58.6％ (41/70).PET/CT与定位CT诊断腹膜转移的灵敏度差异有统计学意义(x2=14.286,P＜0.001).70例腹腔积液患者中仅21例腹腔积液中见癌细胞,其余患者细胞学检查均为阴性,腹腔积液细胞学对腹膜转移诊断的灵敏度、特异性和准确性分别为43.8％ (21/48)、100％ (22/22)和61.4％ (43/70);PET/CT与细胞学检查对腹膜转移诊断的灵敏度差异有统计学意义(x2=13.885,P＜0.001).PET/CT检查结果与最后诊断结果吻合度较强(Kappa=0.776,P＜0.001),定位CT、腹腔积液细胞学检查结果与最后诊断结果吻合度均较弱(Kappa值分别为0.236和0.328,P均＜0.05).结论 18F-FDG PET/CT显像对不明原因腹腔积液患者腹膜转移诊断有重要临床价值,可用于不明原因腹腔积液的良恶性鉴别诊断.     

18F-FDG PET/CT显像对小肠腺癌的诊断价值

目的 探讨18F-FDG PET/CT全身显像对小肠腺癌(SIA)的诊断价值.方法 回顾29例SIA(男17例,女12例)、21例小肠淋巴瘤(SIL;男15例,女6例)及10例小肠结核(SIT;男4例,女6例)的18F-FDG PET/CT显像资料,采用目测法和半定量方法(SUVmax)分析3种疾病PET/CT显像特点.计量资料差异比较用单因素方差分析,率的比较行x2检验.结果 (1) PET/CT图像上SIA多表现为小肠局部团块状、结节状高代谢灶,典型的SIL为小肠局部环形异常放射性浓聚灶,SIT多呈结节状、条状高代谢灶、病灶呈“跳跃性”分布;SIA的SUVmax为8.44±3.82,低于SIL(11.54±4.02; F=86.96,t=2.77,均P＜0.01),与SIT的8.61±2.99差异无统计学意义(t=0.11,P＞0.05).(2)SIA、SIL和SIT的灶周淋巴结肿大检出率分别为72.41％ (21/29)、85.71％(18/21)和70.00％ (7/10) (x2=1.50,P＞0.05);SIA的灶周肿大淋巴结SUVmax为5.59±2.86,明显低于SIL的11.10±5.72(F=56.56,t=3.85,均P＜0.01),与SIT的5.63±3.36差异无统计学意义(t=0.30,P＞0.05).PET/CT显像对SIA的灶周淋巴结肿大检出率明显高于CT(41.38％,12/29;x2=5.69,P＜0.05).(3)55.17％(16/29)的SIA有小肠外转移灶;66.67％(14/21)的SIL有小肠外病灶,以全身多发淋巴结浸润多见;80.00％(8/10)的SIT有腹腔外结核灶;三者小肠外病灶检出率差异无统计学意义(x2=2.13,P＞0.05).(4)29例SIA中15例(51.72％)累及回肠,8例(27.59％)累及空肠,4例(13.79％)空肠回肠同时受累,2例(6.90％)空肠十二指肠同时受累,病灶分布差异有统计学意义(x2=18.16,P＜0.01).(5)29例SIA中单原发癌8例(27.59％),转移性癌14例(48.28％),7例(24.14％)考虑为双原发癌.(6)以病理、诊断性治疗和临床随访结果为标准,18F-FDG PET/CT显像诊断SIA的灵敏度为93.10％(27/29),特异性为80.00％(8/10).结论 18F-FDG PET/CT全身显像可用于SIA的鉴别诊断,可为单原发、多原发及转移性SIA诊断提供依据.     

Value of 18F-FDG PET/CT in the Detection of Ovarian Malignancy

Purpose

Ovarian cancer is a leading cause of gynecologic malignancy. As symptoms of ovarian cancer are nonspecific, only 20 % of ovarian cancers are diagnosed while they are still limited to the ovaries. Thus, early and accurate detection of disease is important for an improved prognosis. For the accurate and effective diagnosis of ovarian malignancy on ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT), we analyzed several parameters, including visual assessment.

Method

A total of 51 peritoneal lesions in 19 patients who showed ovarian masses with diffuse peritoneal infiltration were enrolled. Twelve patients were confirmed to have ovarian malignancy and seven patients with benign disease by pathologic examination. All patients were examined by ¹⁸F-FDG PET/CT, and an additional 2-h delayed ¹⁸F-FDG PET/CT was also performed for 15 patients with 42 peritoneal lesions. We measured semiquantitative parameters including maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on a 1-h initial ¹⁸F-FDG PET/CT image (Parameter₁) and on a 2-h delayed image (Parameter₂). Additionally, retention indices of each parameter were calculated, and each parameter among the malignant and benign lesions was compared by Mann-Whitney U test. We also assessed the visual characteristics of each peritoneal lesion, including metabolic extent, intensity, shape, heterogeneity, and total visual score. Associations between visual grades and malignancy were analyzed using linear by linear association methods. Moreover, a receiver operating characteristic (ROC) curve was analyzed to compare the effectiveness of significant parameters.

Result

In a comparison between the malignant and benign groups in the analysis of 51 total peritoneal lesions, SUVmax₁, SUVmean₁, and TLG₁ showed significant differences. Also, in the analysis of 42 peritoneal lesions that underwent an additional 2-h ¹⁸F-FDG PET/CT examination, SUVmax_1,2, SUVmean_1,2, TLG₂, and the RI of TLG showed significant differences between the malignant and benign groups. MTV did not show significant differences in either the analysis of 51 peritoneal lesions or of 42 lesions. Regarding visual assessments, metabolic intensity, shape, heterogeneity, and total visual score showed an association with malignancy. In the ROC analysis, the AUC of the visual score was larger than the AUC of other parameters in both the analyses of 51 peritoneal lesions and of 42 lesions.

Conclusion

Although further study with a larger patient population is needed, the visual assessment of ¹⁸F-FDG PET/CT imaging has a primary role in the detection of malignancy in ovarian cancer patients with assistance from other semi-quantitative parameters.     

Bilateral Tubo-Ovarian Abscess Mimics Ovarian Cancer on MRI and 18F-FDG PET/CT

A 20-year-old woman, who presented with a several-week history of abdominal pain, was referred for magnetic resonance imaging (MRI) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after an ultrasound showed complex cystic masses arising from both ovaries. The MRI and ¹⁸F-FDG PET/CT imaging characteristics of the ovarian masses were strongly suspicious for malignancy, and the masses were surgically removed. Histopathological evaluation revealed a bilateral tubo-ovarian abscess, with no evidence of malignancy. This case highlights a potentially serious pitfall in the evaluation of suspicious pelvic masses by ¹⁸F-FDG PET/CT, whereby a complex bilateral tubo-ovarian abscess may mimic the PET/CT imaging characteristics of an ovarian or pelvic malignancy.     

Prognostic Value of Metabolic Activity Measured by 18F-FDG PET/CT in Patients with Advanced Endometrial Cancer

Purpose

We evaluated the potential prognostic value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer.

Methods

Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUVmax) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUVmax of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method.

Results

A total of 42 patients with a median age of 55.5 years (range 32–76 years) were included. Twenty-nine percent (n = 12) of patients were premenopausal and 71 % (n = 30) were postmenopausal. The average SUVt was 12.9 (range 1.8–36.5), and the average SUVn was 7.3 (range 2.0–22.5). Median follow-up time was 25.9 months (range 1–84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P = 0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P = 0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt ≥ 9.5 or SUVn ≥ 7.3 showed a significantly longer OS than the other groups.

Conclusions

FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn.     

18F-FDG PET-CT显像在预测肺癌淋巴结分期中的价值

目的:探究18F-FDG PET-CT显像在肺癌患者淋巴结分期中的预测价值。方法:以35例经手术病理证实为肺癌患者的PET-CT资料及临床资料为研究对象。在PET-CT原发灶及纵隔淋巴结各区最浓聚的部位勾画感兴趣区,得出SUVmax.以淋巴结转移进行分组,采用t检验、Wilcoxon rank-sum检验及四格表资料的Fisher确切概率法分析组间淋巴结SUVmax、淋巴结与原发灶SUVmax的比值(SUVratio)及临床特征的差异。用ROC曲线对PET/CT的预测价值进行分析。结果:患者年龄、性别、吸烟史、组织类型与肺门、纵隔淋巴结转移无显著相关(P>0.05)。转移淋巴结的SUVmax较非转移淋巴结显著升高,差异有统计学意义(P<0.05),而淋巴结的SUVratio与淋巴结转移无明显相关(P>0.05)。取淋巴结SUVmax的最佳阈值,假阴性患者中的肺癌原发灶SUVmax偏低,假阳性患者比假阴性患者中的吸烟率高,但不具有显著统计学意义(P>0.05)。结论:淋巴结SUVmax可以为临床判断淋巴结转移提供定量指标。结合患者的临床病理特征判断淋巴结的转移可能从--定程度上减少假阳性率及假阴性率。     

The Diagnostic Value of 18F-FDG PET/CT Imaging in Preoperative Staging of Colorectal Cancer

目的 探讨18F-FDG PET/CT在结直肠癌术前TNM分期中的应用价值.资料与方法 33例疑结直肠肿瘤患者均于手术治疗前行全身PET/CT扫描,将患者PET/CT检查结果与手术病理学检查结果进行比较分析.结果 PET/CT诊断结直肠癌原发灶的敏感性、准确性分别为100％和96.97％;PET/CT对术前结直肠癌侵犯局部浆膜、淋巴结转移、远处转移及TNM分期的准确性分别为75.00％、78.12％、96.87％和71.87％,经Kappa一致性检验,PET/CT 上述诊断结果与手术病理学检查结果具有较好的一致性(0.429,0.559,0.920,0.619,P均＜0.05).结论 结直肠癌18F-FDG PET/CT术前检查,是结盲肠癌的术前临床分期中有效的影像学评价手段.     

自身免疫性胰腺炎的18F-FDG PET/CT特征

目的 提高对自身免疫性胰腺炎(AIP)的18F-FDG PET/CT特征的认识.方法 回顾性分析2003年9月到2014年12月间行18F-FDG PET/CT检查的9例AIP患者的临床资料.结果 9例AIP患者胰腺内均显示18F-FDG高摄取病灶,其中6例为全胰腺弥漫性18F-FDG摄取;3例为局灶性FDG摄取;标准摄取值的最大值(SUVmax)为7.0±2.3(4.0～10.2).8例患者在同机CT平扫上呈现全胰腺弥漫性肿大、1例呈现胰头局限性增大.所有患者胰腺病灶内均未见液化坏死及钙化表现,均未出现周围血管包埋改变及胰腺周围液体渗出.2例显示胰腺周围包膜样结构.3例患者出现胰腺外受累,包括前列腺受累3例,右肾受累1例,双侧颌下腺受累1例,胰周及腹膜后淋巴结受累2例.7例患者伴有胆道梗阻.结论 AIP在18F-FDG PET/CT显像有其特征性的形态学改变及代谢变化,识别这些特征有助于AIP的诊断.     

Staging and Follow-up of Lacrimal Gland Carcinomas by 18F-FDG PET/CT Imaging

ABSTRACT: A 74-year-old man with right eye proptosis, diplopia, and orbital discomfort for 3 to 4 months underwent biopsy, the specimen of which showed transitional cell carcinoma of the lacrimal gland. F-FDG PET/CT was also performed for staging purposes. Six months after orbital exenteration, a follow-up CT scan demonstrated soft tissue thickening along the nasal bridge but could not differentiate between postsurgical changes and cancer recurrence. A concurrent PET/CT scan did not show any evidence of abnormal metabolic activity, further emphasizing the higher accuracy of PET/CT in staging and restaging of head and neck cancers. An annual follow-up scan was still negative for active disease.