Surgery promotes the development of endometriosis. Xishi Liu Shanghai OB/GYN Hospital Fudan University Shanghai, China
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1 Surgery promotes the development of endometriosis Xishi Liu Shanghai OB/GYN Hospital Fudan University Shanghai, China
2 Surgery Surgery is now a well accepted treatment modality Surgery is an effective treatment for Cancer Endometriosis Women tend to receive more surgeries Gynecological operations Plastic surgeries Lipo suction
3 The downside of surgery A trauma Carries its own risk of mortality and morbidity Risk of complications Blood loss, transfusion, hypothermia, and certain anesthesia can impact negatively on Cell-mediated immunity Thus promoting metastasis Laparotomy induces more stress hormones than laparoscopy (Muzii et al.
4 Documented risk of surgery Breast augmentation surgery increases the risk of stomach (SIR = 2.65) cervix (SIR = 3.18) vulva (SIR = 2.51) brain (SIR = 2.16) leukemia (SIR = 2.19) (Brinton et al. 2001) Hysterectomy increases the risk of renal cancer (OR=1.8 ( )) (Gago- Dominguez et al. 1999) Surgical stress promotes metastasis (Sood et al. 2012)
5 Does surgery increase the risk of developing endometriosis?
6 Experimental design Induction Surgery Sacrifice 48 female mice No surgery Mastectomy Laparotomy Lesion size, ADRB2, VEGF, MVD (CD31), PCNA Hotplate test
7 A: Lesion weight by groups Total lesion weight (g) * * Control Mastectomy Laparotomy
8 B: Kinetics of mean hotplate latency Hotplate latency (sec) CM L Induction Surgery C M L Control Mastectomy Laparotomy * C M L Time since surgery(day)
9 Representative immunostaining results
10 A: ADRB2 Staining level *** ** Control Mastectomy Laparotomy
11 B: PCNA Staining level ** ** Control Mastectomy Laparotomy
12 ADRB1 ** Staining level Control Mastectomy Laparotomy
13 ADRA1 Staining level Control Mastectomy Laparotomy
14 ADRA2 Staining level Control Mastectomy Laparotomy
15 Is intervention possible?
16 The effect of surgery on the development of endometriosis Alzet pumps implanted Randomization Induction Surgery 60 female Blb/C mice PBS Mastectomy + PBS Laparotomy + PBS Propranolol Mastectomy + Propranolol Hotplate test, bodyweight Laparotomy + Propranolol Sacrifice Lesion size IHC: ADRB2, VEGF, MVD (CD31), PCNA Day
17 A: Baseline bodyweight B: Bodyweight 2w post induction Bodyweight (g) p=0.89 Bodyweight (g) p=0.24 PBS Mast+PBS Lap+PBS Pro Mast+Pro Lap+Pro PBS Mast+PBS Lap+PBS Pro Mast+Pro Lap+Pro C: Bodyweight 2w after treatment D: Change in Bodyweight post induction Bodyweight (g) p=0.01 Change p=0.01 PBS Mast+PBS Lap+PBS Pro Mast+Pro Lap+Pro PBS Mast+PBS Lap+PBS Pro Mast+Pro Lap+Pro
18 A: Total lesion size by groups Total lesion weight (g) * *** CT M L P MP LP
19 B: Kinetics of mean hotplate latency Hotplate latency (sec) Mm L CP l Induction P Cm Ll M Surgery C M L P m l PBS Mast+PBS Lap+PBS Pro Mast+Pro Lap+Pro P C m l ** M L Time since surgery(day)
20 Representative immunostaining results
21 A: ADRB2 Staining level *** *** CT M L P MP LP
22 B: PCNA Staining level *** *** CT M L P MP LP
23 C: VEGF Staining level * CT M L P MP LP
24 D: Microvessel density (CD31) *** ** Staining level CT M L P MP LP
25 F: ADRA1 Staining level CT M L P MP LP
26 G: ADRA2 Staining level CT M L P MP LP
27 How about humans?
28 A hospital-based case-control study Factor Controls (n=212) (Benign gynecologic diseases) Cases (n=208) (Ovarian endometriomas) P-value Age (in years) 33.3(±5.3) 34.0 (±5.2) 0.10 Parity Dysmenorrhea None Mild Moderate Severe Infertility No Yes 57 (26.9%) 65 (30.7%) 90 (42.5%) 136 (64.2%) 66 (31.1%) 10 (4.7%) 0 (0.0%) 207 (99.5%) 5 (0.5%) 64 (30.8%) 53 (25.5%) 91 (43.8%) 74 (35.6%) 77 (37.0%) 37 (17.8%) 20 (9.6%) 190 (91.3%) 18 (8.7%) 0.46 <
29 Information collected Demographic information Education, marital status, occupation, OC use, smoking status, Reproductive history Gravidity, # of abortions, # of C-sections Surgical history # of abdominal surgeries, # of laparoscopic surgeries, # of other surgeries Total # of surgeries
30 Most interesting result Abdominal surgery (Post-menarche) None Once Twice Controls (n=212) Cases (n=208) P-value 208 (98.1%) 4 (1.9%) 0 (0.0%) 197 (94.7%) 10 (4.8%) 1 (0.5%) Crude OR=2.90 ( ) Multivariate logistic regression indicates that OR=3.40 ( ) Post-menarche surgery is a risk factor for the development of endometriosis
31 Conclusions Surgery accelerates the development of endometriosis in mouse Likely through ADRB2-mediated angiogenesis and proliferation Open abdominal surgery is associated with increased risk of developing endometriosis in humans (OR=3.4 ( )) β-blockade seems to be effective in abolishing the promoting effect of surgery
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