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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (5): 981-990. doi: 10.19723/j.issn.1671-167X.2022.05.027

• 论著 • 上一篇    下一篇

副肿瘤性天疱疮合并实体肿瘤的危重症患者术后远期结局的影响因素

潘佳忻1,朱赛楠2,李双玲1,*(),王东信1,3   

  1. 1. 北京大学第一医院重症医学科, 北京 100034
    2. 北京大学第一医院医学统计室, 北京 100034
    3. 北京大学第一医院麻醉科, 北京 100034
  • 收稿日期:2022-06-30 出版日期:2022-10-18 发布日期:2022-10-14
  • 通讯作者: 李双玲 E-mail:lishuangling888@hotmail.com
  • 作者简介:李双玲，主任医师，副教授，硕士研究生导师，博士，现任北京大学第一医院重症医学科常务副主任。主要研究方向：危重患者急性肾损伤发生危险因素及预测模型，人羊膜上皮细胞治疗脓毒症急性肾损伤；危重患者机械通气时镇静对于谵妄和睡眠的影响；脓毒症血流感染诊断和预后评估、腹腔真菌感染诊断新技术等。已在中文核心期刊发表论文30余篇，SCI论文10余篇。现主持中国卫生信息与健康医疗大数据学会重症感染镇痛镇静大数据专项研究，中央高水平医院临床科研跨学科交叉研究专项“基于双层微孔阵列滤膜预处理实时荧光定量聚合酶链式反应检测诊断重症医学科腹腔念珠菌感染的多中心前瞻性队列研究”，作为分中心负责人现主持国家科技部“主动健康和老龄化科技应对”重点研发计划中的子课题“建立老年血流感染的防控体系”、首都卫生发展科研专项“抗Xa监测危重患者低分子肝素预防静脉血栓栓塞症的随机对照试验研究”等。任职中国医师协会重症医学会委员、北京医师协会重症医学专科医师分会常务理事、北京医学会重症分会委员、北京生理学会危重病专业委员会副主任委员、北京抗癌协会肿瘤重症专业委员会副主任委员、中国人体健康科技促进会重症医学与器官支持专业委员会常务委员、北京重症超声研究会副秘书长等

Factors associated with long-term survival in critically ill patients following surgery for solid tumors complicated with paraneoplastic pemphigus

Jia-xin PAN1,Sai-nan ZHU2,Shuang-ling LI1,*(),Dong-xin WANG1,3   

  1. 1. Department of Critical Care Medicine, Peking University First Hospital, Beijing 100034, China
    2. Department of Biostatistics, Peking University First Hospital, Beijing 100034, China
    3. Department of Anesthesiology, Peking University First Hospital, Beijing 100034, China
  • Received:2022-06-30 Online:2022-10-18 Published:2022-10-14
  • Contact: Shuang-ling LI E-mail:lishuangling888@hotmail.com

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摘要：

目的: 副肿瘤性天疱疮合并实体肿瘤的重症患者通常需要在手术后收住重症医学科(intensive care unit，ICU)治疗，这类患者的长期死亡率较高。本研究对这类患者的临床特点及远期预后的影响因素进行分析。方法: 回顾性分析2005年1月至2020年12月间63例副肿瘤性天疱疮合并实体肿瘤、手术后收住ICU重症患者的临床和实验室资料，并对患者的生存状况进行随访。结果: 63例患者中，原发肿瘤为Castleman病的占79.4%，其他病理类型为20.6%；皮损程度在重度-广泛的占69.8%，其他皮损程度占30.2%；合并闭塞性细支气管炎的占44.4%，不合并的占55.6%。23.8%的患者并发术后真菌感染，无真菌感染占76.2%。术后中位随访时间为95个月，25例患者在研究期间死亡，术后1年、3年、5年生存率分别为74.6%(95%CI 63.8%~85.4%)、67.4%(95%CI 55.6%~79.2%)和55.1%(95%CI 47.9%~62.3%)。通过对分类因素采用Log-rank法进行单因素分析结果表明：年龄＞40岁(P=0.042)、发病后体质量下降＞5 kg(P=0.002)、术前白蛋白 < 30 g/L(P < 0.001)、并发闭塞性细支气管炎(P=0.002)、围术期存在真菌感染(P＜0.001)的患者死亡率增加；Cox单因素分析显示术前体质量下降>5 kg(P=0.005)、术前白蛋白 < 30 g/L(P < 0.001)、术前合并闭塞性细支气管炎(P=0.009)、术前肺部细菌感染(P=0.007)、手术时间长(P=0.048)、术后入ICU时氧合指数(P=0.012)和白蛋白(P=0.010)、血红蛋白浓度低(P=0.035)、入ICU后急性生理学及慢性健康状态评分(acute physiology and chronic health evaluation, APACHE Ⅱ, P=0.001)、序贯器官衰竭评分(sequential organ failure assessment, SOFA, P=0.010)，以及术后真菌感染都是影响远期存活的危险因素(P < 0.001)。Cox回归模型进行多因素分析结果表明，术前体质量下降＞5 kg(HR 4.44; 95%CI 1.47~13.38; P=0.008)、术前白蛋白 < 30 g/L(HR 4.38; 95%CI 1.72~11.12; P=0.002)、术前合并闭塞性细支气管炎(HR 2.69; 95%CI 1.12~6.50; P=0.027)及术后并发真菌感染(HR 4.85; 95%CI 2.01-11.72; P＜0.001)是术后死亡的独立危险因素。结论: 因副肿瘤性天疱疮合并实体肿瘤而接受手术治疗的重症患者术后的5年存活率约为55.1%，术前体质量下降＞5 kg、白蛋白 < 30 g/L、合并闭塞性细支气管炎和术后并发真菌感染是术后近远期死亡风险增加的影响因素。

关键词: 副肿瘤性天疱疮, Castleman病, 闭塞性细支气管炎

Abstract:

Objective: Critically ill patients with solid tumors complicated with paraneoplastic pemphigus are usually treated in intensive care units (ICU) for perioperative management after surgical treatment. In this study, the clinical characteristics and predictors of long-term prognosis of these critically ill patients were analyzed. Methods: the clinical and laboratory data of 63 patients with solid tumors complicated with paraneoplastic pemphigus admitted to ICU from 2005 to 2020 were retrospectively analyzed, and the survival status of the patients were followed up. Results: Among the 63 patients, 79.4% had Castleman disease as the primary tumor, and 20.6% with other pathological types; 69.8% had severe-extensive skin lesions, and 30.2% had other skin lesions; the patients with bronchiolitis obliterans accounted for 44.4%, and 55.6% were not merged. Postoperative fungal infection occurred in 23.8% of the patients, and 76.2% without fungal infection. The median follow-up time was 95 months, and 25 patients died during the study period. The 1-year, 3-year and 5-year survival rates were 74.6% (95%CI 63.8%-85.4%), 67.4% (95%CI 55.6%-79.2%) and 55.1% (95%CI 47.9%-62.3%), respectively. The log-rank univariate analysis showed that the patients had age>40 years (P=0.042), preoperative weight loss>5 kg (P=0.002), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.002), and perioperative fungal infection (P < 0.001) had increased mortality. Cox univariate analysis showed that preoperative weight loss >5 kg (P=0.005), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.009), preoperative bacterial pulmonary infection (P=0.007), prolonged surgical time (P=0.048), postoperative oxygenation index (P=0.012) and low albumin (P=0.010) and hemoglobin concentration (P=0.035) in ICU, acute physiology and chronic health evaluation (APACHE Ⅱ) score (P=0.001); sequential organ failure assessment (SOFA) score (P=0.010), and postoperative fungal infection (P < 0.001) were risk factors for long-term survival. Cox regression model for multivariate analysis showed that preoperative weight loss > 5 kg (HR 4.44; 95%CI 1.47-13.38; P=0.008), and preoperative albumin < 30 g/L (HR 4.38; 95%CI 1.72-11.12; P=0.002), bronchiolitis obliterans (HR 2.69; 95%CI 1.12-6.50; P=0.027), and postoperative fungal infection (HR 4.85; 95%CI 2.01-11.72; P < 0.001) were independent risk factors for postoperative mortality. Conclusion: The 5-year survival rate of critically ill patients undergoing surgery for paraneoplastic pemphigus combined with solid tumors is approximately 55.1%, with preoperative weight loss > 5 kg, albumin < 30 g/L, bronchiolitis obliterans and postoperative fungal infection were associated with an increased risk of near- and long-term postoperative mortality.

Key words: Paraneoplastic pemphigus, Castleman disease, Bronchiolitis obliterans

中图分类号: 

  • R593.2

表1

患者一般临床资料"

Items Total (n=63) Survivors (n=38) Non-survivors (n=25)
Baseline characteristics
Age/years, ${\bar x}$±s 41.7±16.2 39.6±16.3 46.8±14.8
Age>40 years 33 (52.4%) 16 (42.1%) 17 (68.0%)
Male 25 (39.7%) 16 (42.1%) 9 (36.0%)
BMI /(kg/m2), ${\bar x}$±s 20.6±3.3 20.5±3.1 20.8±3.5
Preoperative weight loss>5 kg 41 (65.1%) 20 (52.6%) 21 (84.0%)
Preoperative comorbidities 10 (15.9%) 6 (15.8%) 4 (16.0%)
  Coronary heart disease 5 (7.9%) 3 (7.9%) 2 (8.0%)
  Hypertension 7 (11.1%) 6 (15.8%) 1 (4.0%)
  Diabetes 3 (4.8%) 1 (2.6%) 2 (8.0%)
  Cerebral infarction 3 (4.8%) 2 (5.3%) 1 (4.0%)
  Chronic bronchitis 4 (6.3%) 2 (5.3%) 2 (8.0%)
Smoking 4 (6.3%) 2 (5.3%) 2 (8.0%)
Preoperative albumin/(g/L), ${\bar x}$±s 30.9±4.7 32.3±3.7 26.8±5.0
Preoperative data of PNP
Tumor location
  Mediastinum 31 (49.2%) 17 (44.7%) 14 (56.0%)
  Lung 1 (1.6%) 1 (2.6%) 0 (0.0%)
  Abdominal cavity 11 (17.5%) 7 (18.4%) 4 (16.0%)
  Pelvis cavity 8 (12.7%) 5 (13.2%) 3 (12.0%)
  Post-peritonium 10 (15.9%) 7 (18.4%) 3 (12.0%)
  Multiple tumors 2 (3.2%) 1 (2.6%) 1 (4.0%)
Pathological type
  CD hyaline vascular 40 (63.5%) 26 (68.4%) 14 (56.0%)
  CD plasmacytic 2 (3.2%) 0 (0.0%) 2 (8.0%)
  CD mixed 8 (12.7%) 4 (10.5%) 4 (16.0%)
  Thymoma 10 (15.9%) 5 (13.2%) 5 (20.0%)
  Follicular dendritic cell sarcoma 3 (4.8%) 3 (7.9%) 0 (0.0%)
Types of skin lesions
  Erythema multiforme-like 24 (38.1%) 13 (34.2%) 11 (44.0%)
  Pemphigoid-like 27 (42.9%) 17 (44.7%) 10 (40.0%)
  Lichen planus-like 6 (9.5%) 4 (10.5%) 2 (8.0%)
  Pemphigus-like 5 (7.9%) 3 (7.9%) 2 (8.0%)
  Graft-versus-host disease-like 1 (1.6%) 1 (2.6%) 0 (0.0%)
PDAI
  Moderate (< 15 scores) 19 (30.2%) 12 (31.6%) 7 (28.0%)
  Significant (15-45 scores) 13 (20.6%) 7 (18.4%) 6 (24.0%)
  Extensive (>45 scores) 31 (49.2%) 19 (50.0%) 12 (48.0%)
Serological biomarkers
  DSG1(+) 19 (46.3%) [22] 8 (36.4%) [16] 11 (57.9%) [6]
  DSG3 (+) 8 (17.0%) [22] 3 (13.6%) [16] 5 (26.3%) [6]
  Antibodies of myasthenia gravis (+) 10 (29.4%) [29] 5 (23.8%) [17] 5 (38.5) [12]
  BP180 (+) 26 (81.3%) [31] 15 (83.3%) [20] 11 (78.6%) [11]
Clinical complications of PNP
  Dyspnea 38 (60.3%) 20 (52.6%) 14 (56.0%)
  BO 28 (44.4%) 11 (28.9%) 17 (68.0%)
  Myasthenia gravis 7 (11.1%) 4 (10.5%) 3 (12.0%)
  Preoperative bacterial pulmonary infection 8 (12.7%) 2 (5.3%) 6 (24.0%)
  Preoperative fungal infection 4 (6.3%) 1 (2.6%) 3 (12.0%)
Treatment of PNP
  Corticosteroids 60 (95.2%) 35 (92.1%) 25 (100.0%)
  Immunosuppressive agents 5 (7.9%) 2 (5.3%) 3 (12.0%)
  Gammaglobulin 30 (47.6%) 16 (42.1%) 14 (56.0%)
Perioperative data
Onset-to-surgical excision time/month, M(Q1, Q3) 5 (3, 10) 5 (3, 11) 4 (3, 8)
Surgical time/h, M(Q1, Q3) 3.7 (2.3, 5.2) 3.1 (2.0, 5.0) 4.0 (3.0, 5.6)
Intraoperative bleeding volume/mL, M(Q1, Q3) 300 (100, 850) 300 (100, 500) 300 (150, 1350)
Laboratory findings at ICU admission, ${\bar x}$±s
  WBC/(×109/L) 8.9±3.5 8.6±3.4 9.3±3.6
  PaCO2/mmHg 45±10 45±9 46±13
  OI/mmHg 227±100 256±112 183±55
  Albumin/(g/L) 25.0±4.2 26.2±3.8 23.2±4.3
  Hgb /(g/L) 98.1±16.9 101.7±14.9 92.4±18.5
Worst score in ICU
  APACHE Ⅱ, M(Q1, Q3) 8 (6, 12) 7 (4, 8) 10 (6, 13)
  SOFA, M(Q1, Q3) 2 (2, 3) 2 (1, 3) 3 (2, 3)
Postoperative infection
  High PCT 26 (50.0%) [11] 12 (38.7%) [7] 14 (66.7%) [4]
  Fungal infection 15 (23.8%) 4 (10.5%) 11 (44.0%)
Outcomes
MVT/h, M(Q1, Q3) 14 (4, 67) 9 (4, 23) 23 (12, 86)
ICU stay/d, M(Q1, Q3) 3 (1, 4) 3 (1, 4) 3 (1, 19)
LHS/d, M(Q1, Q3) 34 (14, 67) 22 (14, 42) 49 (25, 79)
Follow-up time/m, M(Q1, Q3) 95 (75, 132) 92 (74, 132) 114 (81, 130)
In-hospital deaths 9 (14.3%) 9 (36.0%)
Post-discharge deaths 16 (25.4%) 16 (64.0%)
Survival times/month, M(Q1, Q3) 34 (1, 143) 42 (32, 70) 5 (2, 25)

表2

63例副肿瘤性天疱疮合并实体肿瘤患者总生存的单因素分析"

Items Survival rate/% Log-rank Cox univariate analysis
1 year 5 years χ2 P value HR (95%CI) P value
Baseline characteristics
Age/years 4.145 0.042*
  ≤40 79.6 69.2 1
  >40 69.7 41.1 2.23 (1.00-5.40) 0.051*
Gender 0.344 0.558
  Female 68.4 52.5 1
  Male 79.2 59.9 0.79 (0.35-1.78) 0.563
Preoperative weight loss 9.567 0.002*
  ≤5 kg 95.5 76.5 1
  >5 kg 63.0 43.7 4.77 (1.60-14.2) 0.005*
BMI/(kg/m2)a 1.02 (0.90-1.15) 0.815
Preoperative comorbiditiesb 1.14 (0.88-1.53) 0.695
Smokingb 1.65 (0.71-2.40) 0.237
Preoperative data of PNP
Preoperative albumin 17.568 < 0.001*
  ≥30 g/L 88.6 72.2 1
   < 30 g/L 55.6 26.7 5.62 (2.24-14.12) < 0.001*
Tumor location 1.974 0.160
  Others 80.6 61.5 1
  Thoracic cavity 68.5 50.4 1.76 (0.78-3.94) 0.170
Pathological type 0.028 0.866
  Others 59.3 59.3 1
  CD 77.9 51.6 0.92 (0.34-2.47) 0.868
Skin lesions type 0.166 0.684
  Others 74.3 51.3 1
  Erythema multiforme-like 74.8 52.2 1.50 (0.68-3.32) 0.318
PDAI 0.267 0.875
  Moderate (< 15 scores) 63.6 53.0 1
  Significant (15-45 scores) 69.2 60.6 0.95 (0.38-2.43) 0.922
  Extensive (>45 scores) 70.8 49.2 0.68 (0.22-2.05) 0.490
Serological biomarkers
  DSG1 1.747 0.186
    DSG1 (-) 77.3 57.5 1
    DSG1 (+) 68.4 33.2 1.82 (0.73-4.53) 0.199
  DSG3 2.744 0.254
    DSG3 (-) 78.8 47.4 1
    DSG3 (+) 75.0 37.5 1.73 (0.62-4.83) 0.297
  BP180 (+)b 0.59 (0.16-2.15) 0.423
  Antibodies of myasthenia gravis 3.710 0.054
    Antibodies of myasthenia gravis (-) 71.6 55.7 1
    Antibodies of myasthenia gravis (+) 45.7 45.7 3.04 (0.92-10.06) 0.069*
Clinical complications of PNP
  Dyspnea 2.816 0.093
    Without 79.5 67 1
    With 71.1 46.2 0.75 (0.34-1.66) 0.481
  BO 9.537 0.002*
    Without 82.5 72.8 1
    With 64.3 33.4 2.97 (1.31-6.75) 0.009*
  Myasthenia gravisb 2.49 (0.93-6.69) 0.070*
  Preoperative bacterial pulmonary infection 3.171 0.074 2.62 (1.42-9.23) 0.007*
    Without 80.3 68.8
    With 75.0 25.0
  Preoperative fungal infectionb 2.05 (0.61-6.90) 0.244
Treatment of PNP
  Corticosteroidsb 0.79 (0.18-3.41) 0.753
  Immunosuppressive agentsb 2.78 (0.82-9.41) 0.100
  Gammaglobulin 0.735 0.391
    Without 78.7 56.4 1
    With 63.2 46.3 1.41 (0.64-3.10) 0.399
Perioperative data
Onset-to-surgical excision time/montha 0.99 (0.95-1.04) 0.668
Surgical time/ha 1.16 (1.00-1.33) 0.048*
Intraoperative bleeding volume/mLa 0.96 (0.66-1.38) 0.943
Laboratory findings at ICU admissiona
  WBC/(×109/L)a 1.05 (0.94-1.18) 0.407
  PaCO2/mmHga 1.01 (0.97-1.05) 0.620
  OI/mmHga 0.99 (0.98-1.00) 0.012*
  Albumin /(g/L)a 0.88 (0.80-0.97) 0.010*
  Hgb /(g/L)a 0.97 (0.95-1.00) 0.035*
Worst score in ICU
  APACHE Ⅱa 1.25 (1.10-1.42) 0.001*
  SOFAa 2.14 (1.20-3.82) 0.010*
Postoperative infection
PCT 3.903 0.048
  Normal PCT 80.6 60.4 1
  High PCT 57.2 37.5 2.41 (0.97-5.98) 0.059*
Fungal infection 14.085 < 0.001*
  Without 81.0 67.1 1
  With 53.3 16.0 6.03 (2.56-14.2) < 0.001*

图1

患者的Kaplan-Meier生存曲线"

表3

Cox多因素风险比例模型预测远期存活的影响因素"

Items Univariate analysis P value Multivariate analysis
HR (95%CI) P value
Age>40 years 0.051
Preoperative weight loss>5 kg 0.005 4.44 (1.47-13.38) 0.008
Preoperative albumin < 30 g/L < 0.001 4.38 (1.72-11.12) 0.002
Antibodies of myasthenia gravis (+) 0.069
PNP with BO 0.009 2.69 (1.12-6.50) 0.027
PNP with myasthenia gravis 0.070
Preoperative bacterial pulmonary infection 0.007
Surgical time/h 0.048
OI/mmHga 0.012
Albumin /(g/L)a 0.010
Hgb/ (g/L)a 0.035
Worst SOFA score in ICU 0.010
Postoperative high PCT 0.059
Postoperative fungal infection < 0.001 4.85 (2.01-11.72) < 0.001
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