What are the protocols for comparing energy devices versus suture ligation of the Deep Venous Complex (DVC) in radical cystectomy?

Protocol for Comparing Energy Devices vs Suture Ligation of DVC in Radical Cystectomy

Study Design Framework

This should be structured as a prospective, randomized controlled trial comparing energy-based devices (electrosurgical/heat-sealing) versus traditional suture ligation for control of the dorsal venous complex during radical cystectomy. 1, 2

Primary Outcomes (Prioritizing Morbidity & Mortality)

• Estimated blood loss (EBL) during DVC control and total procedure 1, 2
• Transfusion requirements (number of patients requiring transfusion and mean units transfused) 1, 2
• 90-day complication rates classified by Clavien-Dindo grade ≤2 and ≥3 3, 4
• 30-day and 90-day mortality rates (target <2% for elective cystectomy) 3

Secondary Outcomes

• Operative time for DVC control and total procedure 1, 2
• Need for adjunctive hemostatic measures (additional suture ligatures, clips) 2
• Device-related complications (thermal injury, vascular injury) 1, 2
• Length of hospital stay 3
• Readmission rates (30-day and 90-day) 3
• Cost analysis (device costs, transfusion costs, complication-related costs) 2

Patient Selection & Inclusion Criteria

Inclusion Criteria

• Age ≥18 years undergoing radical cystectomy for muscle-invasive bladder cancer 3
• Performance status suitable for major surgery (ASA score documented) 3
• All urinary diversion types (ileal conduit, continent cutaneous, orthotopic neobladder) 3

Exclusion Criteria

• Coagulopathy or anticoagulation that cannot be safely held perioperatively 5
• Prior pelvic radiation that may alter tissue planes 3
• Emergency cystectomy (only elective cases) 3
• Robotic or laparoscopic approach (unless stratified separately, as this protocol focuses on open technique) 4

Randomization & Blinding

• 1:1 randomization to energy device (LigaSure, Harmonic, or bipolar sealing device) versus traditional suture ligation 1, 2
• Stratification factors: Age (<60 vs ≥60 years), gender, BMI (<35 vs ≥35 kg/m²), neoadjuvant chemotherapy status 3, 5
• Surgeon blinding not feasible; outcome assessors and data analysts should be blinded 1

Standardized Perioperative Protocol (ERAS Components)

Preoperative Phase

• Neoadjuvant chemotherapy for clinically eligible ≥cT2 MIBC documented 3
• Multidisciplinary team discussion documented 3
• Preoperative counseling with enterostomal therapist for stoma marking 3
• Fasting protocol: Solid food up to 6 hours, clear liquids up to 2 hours before surgery 3, 6
• No mechanical bowel preparation (shown not to improve outcomes) 3
• VTE prophylaxis: Mechanical (sequential compression devices) and pharmacological (low molecular weight heparin) initiated preoperatively 6, 5

Intraoperative Phase

• Antimicrobial prophylaxis: Single dose <1 hour before incision, effective against aerobes and anaerobes 3
• Thoracic epidural analgesia (Th9-11) for 48-72 hours postoperatively 3
• Goal-directed fluid management using Doppler guidance to prevent fluid overload 3, 6
• Standard or extended pelvic lymphadenectomy (minimum: external iliac, internal iliac, obturator nodes) 3
• Normothermia maintenance throughout procedure 3

DVC Control Technique (Intervention)

Energy Device Arm:

• Use designated energy device (LigaSure Impact, Harmonic Scalpel, or equivalent bipolar sealing device) for DVC division 2
• Document number of device applications required 2
• Record any need for adjunctive suture ligatures or clips 2

Suture Ligation Arm:

• Traditional technique using 0 or 2-0 absorbable suture for DVC ligation 1
• Document number of suture ligatures placed 1
• Record any need for additional hemostatic measures 1

Postoperative Phase

• Early nasogastric tube removal (within 24 hours or avoid routine placement) 3
• Multimodal ileus prevention: Gum chewing, early mobilization (day 1), prevention of PONV 3
• Early oral nutrition: Clear liquids day 1, advance as tolerated 3, 6
• Standardized pain management: Epidural analgesia with transition to oral analgesics 3
• Extended VTE prophylaxis for 28 days postoperatively (>50% of VTE events occur after standard prophylaxis cessation) 5

Data Collection & Monitoring

Intraoperative Data

• Estimated blood loss measured by suction canister volume and surgical sponge weight 1, 2
• Operative time: Total time, time for DVC control specifically 1, 2
• Transfusion: Intraoperative packed red blood cells, fresh frozen plasma, platelets 1, 2
• Device costs: Itemized costs for energy devices, staplers, sutures 2

Postoperative Data

• Hemoglobin/hematocrit: Preoperative, postoperative day 1, discharge 1
• Transfusion requirements: Postoperative units transfused 1, 2
• Complications: Prospectively monitored using Clavien-Dindo classification 3
  • Grade I-II: Minor complications not requiring intervention
  • Grade III-V: Major complications requiring intervention, ICU care, or resulting in death
• Specific complications: Hemorrhage requiring reoperation, VTE (DVT/PE), urosepsis, wound complications 3, 5
• Length of stay: Days from surgery to discharge 3
• Readmissions: 30-day and 90-day rates with reasons 3
• Mortality: 30-day and 90-day rates 3, 4

Pathologic Data

• Lymph node yield (minimum 20 nodes for quality indicator) 3
• Surgical margin status (negative soft tissue margins for pT2 disease) 3
• Final pathologic stage 3

Statistical Considerations

Sample Size Calculation

• Primary endpoint: Estimated blood loss difference of 200ml (clinically significant) 1, 2
• Power: 80% to detect difference with alpha 0.05 1
• Expected enrollment: 70-80 patients per arm based on prior studies 1, 2

Analysis Plan

• Intention-to-treat analysis for all randomized patients 3
• Wilcoxon rank sum test for continuous non-parametric data (EBL, operative time) 2
• Chi-square or Fisher's exact test for categorical data (transfusion rates, complications) 1
• Multivariate analysis adjusting for age ≥60 years, female gender, BMI ≥35 kg/m², preoperative platelet count ≥300,000/cc (VTE risk factors) 5
• Cost-effectiveness analysis including device costs, transfusion costs, complication-related costs 2

Quality Indicators & Benchmarks

• 30-day mortality <2% for elective radical cystectomy 3
• 90-day high-grade complication rate: Target <15% for conduit diversion, <28% for continent diversion 4
• Transfusion rate: Historical baseline 20-40%; energy devices may reduce to <20% 1, 2
• Mean EBL: Historical 600-800ml; energy devices target <500ml 4, 2
• Negative surgical margins: >95% for pT2 disease 3
• Lymph node yield: ≥20 nodes (standard template minimum) 3

Critical Pitfalls & Considerations

VTE prophylaxis must extend 28 days postoperatively as 50.6% of thromboembolic events occur after standard prophylaxis cessation 5. High-risk patients (age ≥60, female, BMI ≥35, platelets ≥300,000/cc) require particular vigilance 5.

Device selection matters: LigaSure demonstrated equivalent blood loss to staplers but significantly lower cost ($625 vs $1490) and fewer adjunctive hemostatic measures needed 2. Staplers showed 20% transfusion rate versus historical 40% with suture ligation alone 1.

ERAS protocol implementation should be standardized across both arms to isolate the effect of DVC control technique 3. Document compliance with ERAS components as this affects all perioperative outcomes 3.

Surgeon experience with energy devices varies; consider stratifying by surgeon or requiring minimum case volume with device before enrollment 4, 7.