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Slide 1: Is this a realistic, safe and viable option for improving ovarian cancer cytoreductive surgery? Peritonectomy Alex J Crandon & Marcelo Carraro Nascimento Qld Centre for Gyn. Cancer
Slide 2: Advantages of Cytoreductive Surgery       Generally accepted as the corner stone for treating advanced ovarian cancer Gives most accurate diagnosis & staging Rapidly improves symptoms and QOL Optimises response to chemotherapy May improve host immune response Improves survival
Slide 3: Residual Disease –v- Survival in Advanced EOC Study Zang, RY 2000 Bristow, RE 1999 Munkarah 1997 Sutton, GP 1989 Piver, MS 1988 Hainsworth, J 1988 Louie, KG 1986 Posada, JG 1985 Conte, P 1985 Pohl, R 1984 Delgado, G 1984 Optimal debulking Survival (months) 19 (≤1cm) 38 (≤1cm) 25 (≤2cm) 45 (<3cm) 48 (≤1cm) 72 (≤3cm) 24 (<2cm) 30+ (<2cm) 25+ (<2cm) 45 (<2cm) 45 (<2cm) Suboptimal debulking Survival (months) 8 (>1cm) 10 (>1cm) 15 (>2cm) 23 (≥3cm) 21 (>1cm) 21 (>3cm) 15 (≥2cm) 18 (>2cm) 14 (>2cm) 16 (>2cm) 16 (>2cm)
Slide 4: Optimal Debulking Variously defined in the literature from <0.5cm (Hacker, NF 1983) to ≤3cm (Hainsworth, 1988 & Sutton, 1989)  Consistently associated with better survival  Most studies are retrospective 
Slide 5: QCGC Database New database commissioned in 1994  Prospectively accumulated data on 701 patients with stage 3C epithelial ovarian cancer  Stratified residual disease left at the end of surgery into 6 categories: nil residuum, <1cm, 1-2cm, >2cm but not gross residuum, gross residuum & unknown. 
Slide 6: Stage 3C EOC Breakdown Residual Disease Nil <1cm 1-2cm >2cm Gross Unknown Total Number 135 227 60 45 65 169 701 Percent 19.3 32.4 8.6 6.4 9.3 24.1 100
Slide 7: Residual Disease –v- Disease Specific Survival Ovary 3c - Residual disease 100 90 80 70 60 50 40 30 20 10 0 12 135 227 170 102 192 115 24 36 MONTHS 80 118 62 62 75 39 48 45 38 22 60 32 26 10 95% CI [ 37, 57 ] [ 19, 33 ] [ 8, 23 ] Median 57 Mths 32 Mths 23 Mths 26% (227-26) <1cm 16% (170-10) 1+cm 47% (135-32) Nil Stage IIIC EOC Nil <1cm 1+cm % SURVIVAL
Slide 8: Residual Disease and Relapse Free Survival Ovary 3c - Residual disease 100 90 80 Stage IIIC EOC % RELAPSE FREE 70 60 50 40 30 20 10 0 12 135 227 170 89 145 82 24 36 MONTHS 47 51 21 31 31 12 48 21 19 5 13% (227-14) <1cm 6% (170-3) 1+cm 60 18 14 3 95% CI [ 18, 36 ] [ 8, 18 ] [ 1, 10 ] Median 23 Mths 13 Mths 12 Mths 27% (135-18) Nil Nil <1cm 1+cm
Slide 9: Conclusions Nil residuum have a statistically significantly better overall and relapse free 5 year survival, p<0.001  Once the residuum gets to ≥1cm then it doesn’t matter how much residuum you leave behind  The proportion left with nil residuum needs to be increased 
Slide 10: Management of Advanced Disease Pelvic & omental disease well managed  Tendency to leave paracolic, abdominal wall, sub-diaphragmatic, retro-hepatic and para-splenic disease to be dealt with by chemotherapy  This last decision is obviously detrimental to patient survival 
Slide 11: Peritonectomy Study This is a prospective feasibility study into the techniques of peritonectomy to determine its transferability to surgery for ovarian and primary peritoneal carcinoma  During the course of the study patients with other peritoneal carcinomatoses have been referred for surgery 
Slide 12: Peritonectomy Methodology  Very careful selection of patients for this procedure Relatively fit and well  Three day pre-operative inpatient assessment by anaesthetist, intensivist, medical oncologist & surgeon  Reservations involving 2 or more and the patient doesn’t get done 
Slide 13: Peritonectomy Workup           Full blood count Blood group and antibody screen Coagulation screen Biochemistry and liver function tests Echocardiogram Full lung function tests Nutritional assessment Visit ICU and ward Pathology liaises with Red Cross blood bank Immunise for possible splenectomy (pneumococcus, haemophilus influenzae & meningococcal C)
Slide 14: One Patient Rejected        One woman aged 43 with peritoneal mesothelioma was rejected for surgery Previous left pneumonectomy On admission for work up was found to have a resting tachycardia ~100bpm Echocardiogram showed pulmonary hypertension and tricuspid incompetence Patients father took her to Boston where peritonectomy & HIPC performed Returned to Brisbane 12 weeks later Died of right heart failure 10 days after returning
Slide 15: Peritonectomy Admission Admitted at least 1 day prior to surgery  High nitrogen low residue diet continued (started at home)  Full bowel prep with IV infusion running  Repeat FBC, Biochem & LFT’s, Magnesium  Possible stoma sites marked 
Slide 16: Day of Surgery Transfer to OT by 0700 hr  General anaesthetic  Arterial line  Central line  Oesophageal temperature probe  Indwelling urinary catheter  Patient positioned for surgery on warming air mattress  Intra-operative “echo” 
Slide 17: Peritonectomy Positioning
Slide 18: Peritonectomy Methodology      Long midline incision – assess and decide if proceed to peritonectomy Total omentectomy up to spleen and splenic flexure +/- splenectomy Excise falciform ligament and ligamentum teres, mobilise liver and do right upper quadrant; left upper quadrant; abdominal wall and paracolic gutters; pelvis with retrograde hysterectomy, BSO, pelvic peritonectomy +/- low restorative rectal resection; finish mesentry & small bowel. Insertion naso-jejunal feeding tube All surgery performed by QCGC staff
Slide 19: Important Aspects Harmonic shears for omentectomy and splenectomy saves time & bleeding  The whole surgical team needs to stop every 4 hours and take a break; rehydration and food is important  Peritoneal stripping should be done either with electrodiathermy using 3mm ball on pure cut or Argon plasma coagulator 
Slide 20: Peritonectomy Patients Patient Age Primary Disease Site Ovary Ovary Peritoneum Peritoneum Mesothelioma Ovary Mesothelioma Ovary Appendix Ovary Peritoneum Ovary Stage Operative Time (hrs) 5.5 5 8.5 5 5.75 10 10.25 13 17 10.25 14 7.5 Intra-op Transfusion (units) 0 0 3 0 3 3 0 8 4 7 3 2 Status SB VW MT IK ML SD KC SM VM ES SW PP 54 65 74 59 59 60 40 57 61 66 53 77 3C R 3C 3C 3C R 4R 3C 4R 3C R DR 3C R 3C 3C R FOD Recurrence (L & H) FOD SD DOD FOD FOD FOD ?PD ?PD FOD Died of bowel obstruction
Slide 21: Peritonectomy Extent of Surgery         10 thoracotomies – 6 ICC’s 8 significant diaphragmatic resections 7 subsegmental liver resections 3 cholecystectomies 6 splenectomies, 2 distal pancreatectomies 3 partial cystectomies, 1 ureteric implantation 6 GIT resections; 4 small, 4 large & 1 partial antrectomy 5 HIPC, 4 post operative IPC.
Slide 22: Post Operative Management      All patients admitted to ICU ventilated Ventilatory support for 3 to 8 days ICU stay for 5 to 10 days Post-operative hospital stay 16 to 45 days Naso-jejunal feeding started soon after admission to ICU
Slide 23: Total Peritonectomy Post-operative Complications     No returns to theatre & No operative related deaths (one death at day 34 postop from unresolved functional bowel obstruction) One post-op bleed not requiring surgical intervention One left subphrenic haematoma found 4 weeks post peritonectomy One wound breakdowns
Slide 24: Modified/Subtotal Peritonectomy 7 done to date,  All admitted to ICU  Ventilation 1 to 3 days  1 superficial wound breakdown  One left subphrenic abscess 3 months following surgery  One recto-vaginal fistula several months following surgery (2 months after closure of ileostomy) 
Slide 25: Lessons Learnt      Requires a real team approach Advantages in having an anaesthetist with cardiac/hepatobiliary experience Extent of peritonectomy dependent on disease distribution & prior chemotherapy Liver mobilisation often uncovers covert disease Temperature control can be a problem – use an air mattress circulating warm air
Slide 26: Where could we be? Residual Disease Nil <1cm 1-2cm >2cm Gross Unknown Total Number 158 302 92 78 78 179 886 Percent 17.8 34.1 10.3 8.8 8.8 20.2 100 8.8 8.8 20.2 100 Modified Peritonectomy 60.3
Slide 27: Imagine If over half of our patients with Stage 3C EOC were being debulked to nil residuum with an overall 5-year survival of 47 per cent.
Slide 28: Conclusion 1 from Peritonectomies Peritonectomy is a relatively safe procedure
Slide 29: Conclusion 2 from Peritonectomies If disease can be debulked to 2cm then it can be debulked to nil residuum but however long it takes to get to 2cm it will take 1 to 2 times as long again to get to nil residuum.
Slide 30: Conclusion 3 from Peritonectomies At laparotomy if initial assessment indicates that disease cannot be debulked to nil residuum then limited omentectomy only should be performed with a view to interval debulking if good response to Chemo On present experience modified peritonectomy is a feasible and viable procedure for advanced EO & PP carcinoma and should become the standard of care
Slide 31: Conclusion 4 from Peritonectomies Patient selection for modified peritonectomy remains the most difficult issue in planning operating lists with ovarian cancer cases
Slide 32: Conclusion 5 from Peritonectomies How to train the next generation of Gynaecological Oncologists?