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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (5): 981-990. doi: 10.19723/j.issn.1671-167X.2022.05.027

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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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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

CLC Number: 

  • R593.2

Table 1

General clinical data of patients"

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)

Table 2

Univariate analyses of overall survival in 63 patients with solid tumors complicated with paraneoplastic pemphigus"

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*

Figure 1

Kaplan-Meier survival curve of patients A, preoperative weight loss>5 kg and ≤5 kg (P=0.002); B, preoperative albumin < 30 g/L and ≥30 g/L (P < 0.001); C, with and without bronchiolitis obliterans (P=0.006); D, with and without postoperative fungal infection (P < 0.001). PNP, paraneoplastic pemphigus; BO, bronchiolitis obliterans."

Table 3

Multivariate analysis was performed using Cox proportional hazards model for various predictive factors"

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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