EVIDENCE FOR GYNECOLOGICAL SURGERY

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EVIDENCE FORGYNECOLOGICAL SURGERY

• Neil Johnson
• University of Auckland
• National Womens Health _at_ Auckland Hospital
• Fertility Plus
• Auckland Gynaecology Group
• Endometriosis Auckland

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Societal dangers of the decreasing rates of
gynaecological surgery
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Evidence ForGynaecological Surgery

• Evidence what progress have we made (if any!)
• What is the best available evidence?
• What are the shortcomings in the evidence?

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Societal dangers of the decreasing rates of
gynaecological surgery
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Are rates of gynaecological surgery decreasing?

• Infertility
• IVF has replaced fertility microsurgery
• Gynaecologic Cancer
• Has (a) improved screening and (b) ?
  effectiveness chemo/radioTx led to less cancer
  surgery?
• Urogynae
• Has improved pelvic floor muscle programs (and ?
  Caesarean delivery) led to less incontinence
  surgery?
• Or is there more due to increased
  awareness/acceptability?
• HMB
• Has Mirena reduced hysterectomy for HMB?
• Or simply increased treatment options?

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NZHIS Figures 2005
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NZHIS Figures 2005
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NZHIS Figures 2005
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NZHIS Figures 2005
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NZHIS Figures 2005
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What else has changed?

• More trainees
• Less widespread expertise in
• Fertility surgery
• Cancer surgery
• Incontinence surgery

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Societal Dangers?

• New specialists inadequately trained in surgery?
• Generalists incapable of less common procedures?
• Women suffering from not having an operation?

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Societal Dangers?I dont think so, providing

• New specialists inadequately trained in surgery?
• New structure
• Recognition of need for further surgical training
  for new specialists
• Buddy system
• Mandatory public hospital appointments initially?

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Societal Dangers?I dont think so, providing

• Generalists incapable of less common procedures?
• Sensible referral thresholds to
• Subspecialists
• Special interest surgeons

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Societal Dangers?I dont think so

• Women suffering from not having an operation?
• Wider treatment options
• Non-surgical may be better
• Avoiding surgery avoids surgical complications!

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Evidence What Progress Have We Made?
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Gynaecological Surgery Trials- Cochrane
Systematic Reviews

• Gynaecological Oncology
• 74 reviews protocols
  
• Incontinence
• 110 reviews protocols
• MDSG
• 156 reviews protocols
• Menstrual disorders
• Subfertilty
• Surgery for benign gynaecologic disease

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Gynaecological Surgery Trials- Cochrane
Systematic Reviews

• Gynaecological Oncology
• 74 reviews protocols 2 surgical reviews
• Incontinence
• 110 reviews protocols 6 surgical reviews
• MDSG
• 156 reviews protocols 17 surgical reviews
• Menstrual disorders 3
• Subfertilty 6
• Surgery for benign gynaecologic disease 8

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MDSG Editorial Base
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What is the Best Available Evidence?
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Gynaecological Cancer Surgery Reviews

• Cervix
• Surgery for CIN
• Vulva
• Surgical interventions for early squamous cell
  carcinoma of the vulva
• Ovary
• Laparoscopy versus laparotomy for FIGO stage 1
  ovarian cancer
• Interval debulking surgery for advanced
  epithelial ovarian cancer

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Gynaecological Cancer Surgery Reviews

• Cervix
• Surgery for CIN
• Vulva
• Surgical interventions for early squamous cell
  carcinoma of the vulva
• Ovary
• Laparoscopy versus laparotomy for FIGO stage 1
  ovarian cancer (protocol)
• Interval debulking surgery for advanced
  epithelial ovarian cancer (protocol)

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Surgery for CIN- Martin-Hirsch et al, 1999

• 28 RCTs quasi-randomised studies
• 7 techniques - knife cone, laser conisation,
  LLETZ, laser ablation, cryotherapy single
  double freeze, radical diathermy
• LLETZ gt laser ablation for disease eradication
• LLETZ provided the most reliable specimens for
  histology with the least morbidity
• But no other differences between techniques

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Surgical interventions for early squamous cell
carcinoma of the vulva- Ansink et al, 1999

• 2 observational studies
• Radical local excision safe alternative to
  radical vulvectomy
• Can omit contralateral groin node dissection for
  lateralised tumour
• Triple incision technique is as safe as en bloc
  dissection
• Groin recurrence is increased if femoral node
  dissection is omitted.

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Urogynaecologic Surgery Reviews

• Incontinence
• Open retropubic colposuspension
• Laparoscopic colposuspension
• Traditional suburethral sling operations
• Needle suspension
• Anterior vaginal repair
• Prolapse
• Surgical management of pelvic organ prolapse
• Fistula
• Surgical management of vesicovaginal and/or
  urethrovaginal fisulae

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Urogynaecologic Surgery Reviews

• Incontinence
• Open retropubic colposuspension
• Laparoscopic colposuspension
• Traditional suburethral sling operations
• Needle suspension
• Anterior vaginal repair
• Prolapse
• Surgical management of pelvic organ prolapse
• Fistula
• Surgical management of vesicovaginal and/or
  urethrovaginal fisulae (protocol)

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Open retropubic colposuspension for urinary
incontinence in women- Lapitan et al, 2005

• 39 RCTs, n3,301
• More effective than conservative
  anticholinergic treatment, needle suspension
  anterior repair
• No differences versus suburethral sling
• No patient reported differences from laparoscopic
  colposuspension
• Burch gt MMK

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Laparoscopic colposuspension for urinary
incontinence in women- Moehrer et al, 2000

• 8 RCTs
• Similar patient reported cure versus open
  colposuspension
• Less effective at urodynamic cure
• Two paravaginal sutures more effective than one

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Traditional suburethral sling operations for
urinary incontinence in women- Bezerra et al,
2005

• 13 RCTs, n760
• No differences versus open retropubic suspension,
  needle suspension nor amongst different types of
  suburethral slings
• More effective than anticholinergic treatment

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Bladder neck needle suspension for urinary
incontinence in women- Glazener et al, 2004

• 8 RCTs, n784
• Less effective than open retropubic suspension
• No difference versus suburethral slings

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Anterior vaginal repair for urinary incontinence
in women- Glazener et al, 2001

• 9 RCTs, n932
• Less effective than open retropubic abdominal
  suspension
• No difference versus physical therapy

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Surgical management of pelvic organ prolapse in
women- Maher et al, 2004

• 14 RCTs, n1,004
• Insufficient evidence to assess impact of
  prolapse surgery on continence issues
• With anterior repair
• Adding TVT ? postop stress incontinence
• Adding Vicryl mesh overlay ? recurrent cystocoele

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Menstrual Disorders Reviews of Surgical Techniques

• HMB
• Surgery versus medical therapy
• Endometrial destruction techniques
• Endometrial resection ablation versus
  hysterectomy

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Surgery versus medical therapy for HMB-
Marjoribanks et al, 2006

• 8 RCTs, n821
• No differences were found between surgery and the
  levonorgestrel intrauterine system in improving
  quality of life
• Surgery, especially hysterectomy, is more
  effective than medical treatments at reducing
  menstrual loss at 1 year

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Endometrial destruction techniques for HMB-
Lethaby et al, 2005

• 19 RCTs, n3,285
• Insufficient consistent evidence of differences
  in effectiveness between different techniques.

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Endometrial resection and ablation versus
hysterectomy for HMB- Lethaby et al, 1999

• 5 RCTs, n752
• Hysterectomy ? effectiveness and
  QoL/satisfaction, but ? adverse events.

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Subfertility Surgery Reviews

• General techniques
• Techniques for pelvic surgery
• Postoperative procedures for improving fertility
• ART-related
• Surgical treatment for tubal disease in women due
  to undergo IVF
• Surgical retrieval of sperm prior to ICSI for
  azoospermia
• IVF versus tubal reanastomosis after
  sterilisation
• Specific diagnoses
• Laparoscopic drilling for anovulatory PCOS
• Laparoscopic surgery for endometriosis-related
  subfertility
• Surgical treatment of fibroids for subfertility

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Subfertility Surgery Reviews

• General techniques
• Techniques for pelvic surgery
• Postoperative procedures for improving fertility
• ART-related
• Surgical treatment for tubal disease in women due
  to undergo IVF
• Surgical retrieval of sperm prior to ICSI for
  azoospermia
• IVF versus tubal reanastomosis after
  sterilisation (protocol)
• Specific diagnoses
• Laparoscopic drilling for anovulatory PCOS
• Laparoscopic surgery for endometriosis-related
  subfertility
• Surgical treatment of fibroids for subfertility
  (protocol)

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Techniques for pelvic surgery in subfertility-
Ahmad et al, 2006

• 7 RCTs
• There is no evidence of superior relative
  effectiveness of
• Carbon dioxide laser versus standard techniques
  in adhesiolysis and salpingostomy
• Open versus laparoscopic salpingosomatolysis for
  tubal patency
• Different techniques of salpingostomy
• Thermocoagulation versus electrocoagulation in
  adhesiolysis
• No RCTs examined the effectiveness of
• Infertility surgery versus no treatment or
  alternative treatment
• The use of magnification in tubal surgery

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Postoperative procedures for improving fertility
following reproductive surgery- Johnson et al,
2006

• 5 RCTs
• No evidence of effectiveness for
• Postoperative hydrotubation
• Second-look laparoscopy with adhesiolysis

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Surgical treatment for tubal disease in women due
to undergo IVF- Johnson et al, 2004

• 3 RCTs, n295

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COMPARISON Laparoscopic Surgery on the
Fallopian Tube (all types)
VERSUS No Surgery on the Fallopian
Tube (all types) OUTCOME Total Pregnancy Rate
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Surgical treatment for tubal disease in women due
to undergo IVF- Johnson et al, 2004

• 3 RCTs, n295
• Laparoscopic salpingectomy for hydrosalpinges
  prior to IVF significantly increases the odds of
  pregnancy and live birth

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Techniques for surgical retrieval of sperm prior
to ICSI for azoospermia- Van Peperstraten et al,
2005

• 2 RCTs, n98
• Insufficient evidence to recommend any particular
  testicular sperm retrieval technique
• Ultrasound guided aspiration
• Micropuncture with perivascular nerve stimulation
  gt Microsurgical epididymal sperm aspiration

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Laparoscopic drilling for ovulation induction in
anovulatory PCOS - Farquhar et al, 2003

• 6 RCTs, n313
• No significant difference in pregnancy and
  miscarriage rates between LOD (6 months follow
  up) and gonadotrophin injections (3-6 cycles)
• Significantly fewer multiple pregnancies with LOD

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Laparoscopic surgery for subfertility associated
with endometriosis- Jacobson et al, 2003

• 2 RCTs, n437
• Laparoscopic surgery significantly increases the
  odds live birth plus ongoing pregnancy

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Reviews of Surgery for Benign Disease

• Hysterectomy
• Approach VH versus LH versus AH
• Subtotal versus total
• Endometriosis
• Laparoscopic surgery
• Endometrioma stripping or drainage/coagulation
• Other techniques
• Tubal ectopic pregnancy
• Adhesion prevention
• Pelvic neuroablation

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Surgical approach to hysterectomy for benign
gynaecological conditionsJohnson et al, 2006

• 27 RCTs, n3,643
• LHgtAH less bloodloss, fewer infections, speedier
  recovery
• AHgtLH shorter op, fewer urinary tract injuries
• VH never disadvantageous

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Total versus subtotal hysterectomy for benign
gynaecological conditionsLethaby et al, 2006

• 3 RCTs, n377
• Subtotal less bloodloss, febrile morbidity,
  ongoing cyclical bleeding
• No differences sexual, urinary, bowel dysfunction

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Laparoscopic surgery for pelvic pain associated
with endometriosisJacobson et al, 2001

• 1 RCT, n63
• Improved pain relief at 6 months

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Excisional versus ablative surgery for ovarian
endometriomataHart et al, 2005

• 2 RCTs, n164
• Excision gt Ablation
• ? pain recurrence endometrioma
• ? fertility

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Interventions for tubal ectopic
pregnancyHajenius et al, 2000

• 39 RCTs
• Laparoscopic surgery versus laparotomy
• ? bloodloss, op time, analgesic reqt., hospital
  stay, return to normal activities
• Similar tubal patency, IU preg, repeat ectopic
• Systemic methotrexate versus laparoscopic
  salpingostomy
• ? persistent trophoblast
• ? emergency surgery for tubal rupture

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Barrier agents for preventing adhesions after
subfertility surgery- Farquhar et al, 2006

• 15 RCTs
• ? adhesions
• Interceed
• Seprafilm
• Gore-Tex versus Interceed
• Pain / Pregnancy rates not reported

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Fluid and pharmacological agents for adhesion
prevention after gynaecological surgeryMetwally
et al, 2006

• 18 RCTs, n1,814
• Mostly insufficient evidence for
  fluid/pharmacologic agents
• Hyaluronic acid agents may prevent adhesion
  formation or recurrence

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Surgical interruption of pelvic nerve pathways
for primary and secondary dysmenorrhoeaProctor
et al, 2005

• 9 RCTs, n584
• LUNA effective for dysmenorrhoea where no
  endometriosis present but nil else
• PSN might be effective for midline pain with
  endometriosis

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What are the Shortcomings in the Evidence?
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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Limitations to Completion of Trials

• Patient preference
• The (not so) SMART Study
• Surgeon preference
• LUNA
• Uterine reconstruction
• Uterine septa for (a) infertility (b) RCM?
• Myomectomy
• For (a) HMB (b) pelvic pain (c) infertility?
• Laparoscopic versus open

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Limitations to Applicability of Trials

• Underpowered
• ? Examples hysterectomy et al
• Less relevant at publication as the field has
  advanced
• Eg laparoscopic colposuspension

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Trial Quality

• Randomisation
• Quasi randomised NON randomised
• Allocation concealment
• 3rd party
• Sealed opaque sequentially-numbered envelopes
• Blinding
• Where outcome subjective, eg pain
• Hyst RV 9 trials assessed pain, none blinded

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Biases in Trials

• Funding bias
• Attrition bias eg Hysterectomy RCTs
• Reporting bias
• Publication bias

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Surgical Interventions

• Surgeon effect
• Skill base variable
• Expertise of new op differs from that of old op
• Lap versus open colposuspension
• eVALuate Study
• Surgeon 1 versus Surgeon 2

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Outcomes

• Outcomes that do not assist clinical decision
  making
• Surrogate end-points
• Objective versus patient-centred
• Short versus long term outcomes
• No long term outcomes in hysterectomy trials

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Analysis Errors

• Which statistic odds ratio
• Pooling data from RCTs
• Heterogeneity

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Problems with Trials

• Limitations to completion of trials
• Limitations to applicability of trials
• Quality
• Biases
• Surgical Interventions
• Outcomes
• Analysis
• Conclusions

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Incorrect Conclusions

• Absence of evidence or evidence of absence
• No difference or No effect
• The opposite
• Meta-analysis can find a significant difference
  when the effect is actually small and clinically
  unimportant
• Unsubstantiated
• LLETZ gt laser ablation for CIN

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In Conclusion

• Clinical Trials in Gynaecological Surgery Are
  We Making Progress?
• Yes
• But theres a long way to go
• WE NEED MULTI-CENTRE RESEARCH NETWORKS TO CONDUCT
  LARGE RCTs, POWERED SUFFICIENTLY TO ANSWER THE
  BIG QUESTIONS

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Can the results of RCTs and meta analysis
be applied to individual patients?