Laparoscopische chirurgie bij het pancreascarcinoom: wat is de winst voor de patient? Marc Besselink, Thijs de Rooij m.g.besselink@amc.nl www.pancreaskanker.nl
Conflict of interest Projects described are sponsored by industry (but investigator initiated) This presenter is a fan of laparoscopic surgery
Introduction - Laparoscopy Laparoscopy in general: associated with less blood loss, faster recovery, shorter time to start chemotherapy Laparoscopy standard for many gastrointestinal procedures (esophagus, stomach, liver, colorectal) But.not yet for the pancreas First procedure performed > 20 years ago Laparoscopic distal pancreatectomy Laparoscopic Whipple
Why not? Until recently: low volume, high complex surgery Now: Centralisation in centers >20 Whipples/year DPCG LAELAPS project
Dutch Pancreatic Cancer Group Nationwide collaboration of all 17 Dutch pancreatic centers Open meetings ~4 months Improving care for patients with pancreatic cancer Teaching Training Clinical studies Project focussing on laparoscopic pancreatic surgery
LAELAPS project 1. Laparoscopic distal pancreatectomy (LDP) 1. Nationwide retrospective analysis 2. Nationwide survey 3. Nationwide training 4. Nationwide prospective analysis 5. LEOPARD (RCT LDP vs ODP) 2. Laparoscopic Whipple (LW) 1. Nationwide prospective analysis 2. Nationwide training 3. LEOPARD-2 (RCT LW vs OW)
Laparoscopic distal pancreatectomy Most common indications: Carcinoma IPMN (main duct / side brach) Neuroendocrine tumor Mucinous cystic neoplasm Spleen? Malignant disease: +splenectomy (+2yrs antibiotics) Benign disease: spleen preservation
Equipment
LDP: spleen preserving
LDP for cancer: incl spleen + mesocolon
Evidence? No RCTs Six systematic reviews 1-5 suggested that laparoscopic DP (LDP), as compared to open DP (ODP), is associated with: Less operative blood loss (263-355 ml) 1,2,4,5 Less morbidity (OR 0,7) 1,4,5 Reduced length of stay (3-6 days) 1-5 1. Jin et al. HPB 2012 2. Jusoh et al. Surg Endosc 2012 3. Sui et al. Asian J Surg 2012 4. Venkat et al. Ann Surg 2012 5. Drymousis et al. HPB (Oxford) 2014
But Most studies: LDP patients selected High-volume expert centers No nationwide studies If only looking at case-matched studies 9 : No significant difference in morbidity Only significant difference remaining: hospital stay But hospital stay is easily influenced (bias) 9. Pericleous et al. Pancreas 2012
Ad 1. LAELAPS analysis Nationwide retrospective study (2005-2013) 17 DPCG centers LDP (n=65) vs ODP (n=634) Analyses: 1. Full cohort 2. Matched cohorts (1:1)
DPCG study - Matching Matching based on: Age Sex ASA physical status BMI Indication for surgery Total cohort comparable baseline, except for: History of abdominal surgery Tumor size Matched groups were comparable
DPCG study - Results FULL vs MATCHED FULL COHORT MATCHED 1:1 Primary outcome Major complications 16% vs 29% P=0.02 14% vs 30% P=0.06 Secondary outcomes Blood loss 275mL vs 700mL P<0.001 275mL vs 650mL P=0.06 Splenectomy in non-malignancy 9% vs 40% P<0.001 10% vs 25% P=0.01 Length of postoperative stay 7d vs 9d P=0.001 7d vs 9d P=0.12 SD standard deviation; ICU intensive care unit; IQR interquartile range
Ad 2. LAELAPS survey Survey sent to 30 pancreatic surgeons 90% response rate 50% no experience in LDP 85% would welcome training in LDP 95% would participate in a RCT on LDP vs ODP
Ad 3. LAELAPS training Training in LDP: Proctoring on-site or in AMC March to November 2014 Mr. Mo Abu Hilal (Southampton) 5 centers Marc Besselink (AMC) 10 centers Central training December 2014
Ad 4. LAELAPS prospective Prospective study Inclusion of LDP patients after training of surgeon Since March 2014, 37 inclusions Analysis: December 2014 to January 2015
Ad 4. Prospective LAELAPS: LDP in AMC BASELINE LDP N=16 Male % 50% Age 62 (37-81) BMI 26 (21-33) ASA 1 6% ASA 2 19% ASA 3 75% Abdominal surgery in history 31%
Ad 4. Prospective LAELAPS LDP in AMC Results LDP N=16 Spleen-preservation, % 44% Operative time, min 343(240-404) Blood loss, ml 327 (50-900) Conversion, % 0% Diagnosis, % Malignant 38% Benign 62% Tumor size, mm 31 (10-100) Radical resection, % 81% Pancreatic fistula, % 57% Major complication, % 21% Postoperative stay, days 6 (4-12)
LEOPARD trial LEOPARD Laparoscopic versus Open Distal Pancreatectomy for Symptomatic Benign, Premalignant and Malignant Disease Thijs de Rooij, participating DPCG surgeons, Olivier Busch, Marc Besselink for the Dutch Pancreatic Cancer Group
RCT Aim(s) To compare LDP to ODP concerning time to functional recovery and (cost)effectiveness LEOPARD trial
RCT - Design Randomized controlled, parallel-group, pragmatic, blinded, multicenter superiority trial Inclusion: Adults Elective DP (+ / - splenectomy) Proven / suspected disease distal pancreas Fit to undergo DP Written informed consent Total: 92 patients (functional recovery 8 > 6 days) LEOPARD trial
RCT Primary outcome Time to functional recovery: Restoration mobility independent level Pain control with only oral analgesia Sufficient caloric intake (>50%) No intravenous fluid administration No signs of infection (no fever, normalizing lab) Discharge when patient is willing to go home LEOPARD trial
Laparoscopic Whipple Laparoscopic Whipple next step For surgeons trained in Laparoscopic surgery Pancreatic surgery Laparoscopic distal pancreatectomy Since 4 months in OLVG, Delft, Den Bosch, AMC plans in 3 others centers to start Benefits? LEOPARD trial
Laparoscopic Whipple AMC LEOPARD trial
Literature No RCTs Several expert series with good results Good training essential! American National Quality Program: 1781 Whipples (2011-2012) with 7.4% min invasive Whipple Results: 50% conversion to open Mortality 2.5x higher than open (4.7% vs 1.8%) LEOPARD trial
Ad 4. Prospective LAELAPS LW AMC International proctor: prof. dr. Topal (Leuven) Patient 1 Sex Female Age 69 BMI 25 ASA 1 Operative time, min 515 Blood loss, ml 315 Complications - Postoperative stay 6 Patient 2 Sex Male Age 78 BMI 24 ASA 3 Operative time, min 484 Blood loss, ml 150 Complications DGE Postoperative stay 8+
Take home message Laparoscopic pancreatic surgery for cancer, what is the benefit for the patient? Unclear, no RCTs Expected less blood loss, quicker recovery, chemotherapy Structured program started in the Netherlands: LAELAPS RCTs needed: LEOPARD 1 + 2 will start in 2015 + 2016 LEOPARD trial
Laparoscopische chirurgie bij het pancreascarcinoom: wat is de winst voor de patient? Marc Besselink, Thijs de Rooij m.g.besselink@amc.nl www.pancreaskanker.nl
Costs? LDP as cost-effective as ODP? 2 / 3 studies found non-significant differences 6,7 1 study: cost reduction $3000 per patient 8 But same impact selection bias! 6. AbuHilal et al. Surg Endosc 2012 7. Waters et al. Surgery 2010 8. Fox et al. Surg Endosc 2012
RCT Quality DPCG centers who: Want to participate Completed LAELAPS training Surgeon performed a + b + c: a) 50 advanced laparoscopy b) 20 distal pancreatectomies (open/laparoscopic) c) 5 LDPs nb: DISPACT: 20 distal pancreatectomies LEOPARD trial