Laparoscopische chirurgie bij het pancreascarcinoom: wat is de winst voor de patient?

Transcription

1 Laparoscopische chirurgie bij het pancreascarcinoom: wat is de winst voor de patient? Marc Besselink, Thijs de Rooij

2 Conflict of interest Projects described are sponsored by industry (but investigator initiated) This presenter is a fan of laparoscopic surgery

3 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

4 Why not? Until recently: low volume, high complex surgery Now: Centralisation in centers >20 Whipples/year DPCG LAELAPS project

5 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

6 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)

7 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

8 Equipment

9 LDP: spleen preserving

10 LDP for cancer: incl spleen + mesocolon

11 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 ( ml) 1,2,4,5 Less morbidity (OR 0,7) 1,4,5 Reduced length of stay (3-6 days) Jin et al. HPB Jusoh et al. Surg Endosc Sui et al. Asian J Surg Venkat et al. Ann Surg Drymousis et al. HPB (Oxford) 2014

12 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

13 Ad 1. LAELAPS analysis Nationwide retrospective study ( ) 17 DPCG centers LDP (n=65) vs ODP (n=634) Analyses: 1. Full cohort 2. Matched cohorts (1:1)

14 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

15 DPCG study - Results FULL vs MATCHED FULL COHORT MATCHED 1:1 Primary outcome Major complications 16% vs 29% P= % vs 30% P=0.06 Secondary outcomes Blood loss 275mL vs 700mL P< mL vs 650mL P=0.06 Splenectomy in non-malignancy 9% vs 40% P< % vs 25% P=0.01 Length of postoperative stay 7d vs 9d P= d vs 9d P=0.12 SD standard deviation; ICU intensive care unit; IQR interquartile range

16 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

17 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

18 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

19 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%

20 Ad 4. Prospective LAELAPS LDP in AMC Results LDP N=16 Spleen-preservation, % 44% Operative time, min 343( ) 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)

21 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

22 RCT Aim(s) To compare LDP to ODP concerning time to functional recovery and (cost)effectiveness LEOPARD trial

23 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

24 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

25 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

26 Laparoscopic Whipple AMC LEOPARD trial

27 Literature No RCTs Several expert series with good results Good training essential! American National Quality Program: 1781 Whipples ( ) with 7.4% min invasive Whipple Results: 50% conversion to open Mortality 2.5x higher than open (4.7% vs 1.8%) LEOPARD trial

28 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+

29 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 will start in LEOPARD trial

30 Laparoscopische chirurgie bij het pancreascarcinoom: wat is de winst voor de patient? Marc Besselink, Thijs de Rooij

31 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 Waters et al. Surgery Fox et al. Surg Endosc 2012

32 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