SURGICAL COMPLICATIONS SURGICAL COMPLICATIONS AND BEVACIZUMABAND BEVACIZUMAB

PETER HEWETT MBBS FRACSPETER HEWETT MBBS FRACS

AETIOLOGYAETIOLOGY

Angiogenesis is a critical process in Angiogenesis is a critical process in wound healingwound healing

VEGF is a potent angiogenic factorVEGF is a potent angiogenic factorBevacizumab inhibits VEGF binding to its Bevacizumab inhibits VEGF binding to its

receptorsreceptors Wound healing is compromisedWound healing is compromised

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Animal StudiesAnimal Studies Inhibition of VEGF was found to reduce Inhibition of VEGF was found to reduce

vascular density in capillary beds by 70%vascular density in capillary beds by 70%Fibrin clots and endothelial apoptosis Fibrin clots and endothelial apoptosis

leaving vessels as empty basement leaving vessels as empty basement membrane sleeves.membrane sleeves.

ComplicationsComplications

Grade 3 Proteinuria 1-5%Grade 3 Proteinuria 1-5%Grade 3 or 4 bleeding 1-6%Grade 3 or 4 bleeding 1-6%Delayed wound healing 1-6%Delayed wound healing 1-6%GI perforation 0%-3.3%GI perforation 0%-3.3%Arterial Thrombotic events 0-3%Arterial Thrombotic events 0-3%

Gordon M. Oncology 2005;69(suppl 3):25–33

RISK FACTORSRISK FACTORS In first 6 months of treatmentIn first 6 months of treatment Peptic ulcer diseasePeptic ulcer disease Tumour necrosisTumour necrosis DiverticulitisDiverticulitis ColitisColitis Intraabdominal abscessIntraabdominal abscess Abdominal CarcinomatosisAbdominal Carcinomatosis Pelvic RadiationPelvic Radiation NSAIDNSAID Sugrue et al BRiTE studySugrue et al BRiTE study

TREATMENTTREATMENT

ResuscitateResuscitateOperateOperateDo not anastomose.Do not anastomose.

Scappaticci FA. Surgical wound healing complications in metastaticcolorectal cancer patients treated withbevacizumab. J Surg Oncol 2005;91:173–180

Elective SurgeryElective Surgery

Wound complications have occurred up to Wound complications have occurred up to 56 days after termination of bevacizumab.56 days after termination of bevacizumab.

Withhold for 2 to 3 half lives (40-60 days) Withhold for 2 to 3 half lives (40-60 days) but surgery 28 days after ceasing but surgery 28 days after ceasing bevacizumab is probably safebevacizumab is probably safe

Minor surgeryMinor surgery

No difference in wound complications in No difference in wound complications in venous access device complications venous access device complications implanted within 7 days of starting implanted within 7 days of starting bevacizumab.bevacizumab.

First BEATrial Berry et alFirst BEATrial Berry et al American Society of Clinical Oncology Gastrointestinal Symposium American Society of Clinical Oncology Gastrointestinal Symposium

20052005

Major SurgeryMajor SurgeryWithhold bevacizumab.Withhold bevacizumab.Avoid anastomoses Avoid anastomoses Form stomasForm stomasConsider tension sutures to Consider tension sutures to close abdominal wall.close abdominal wall.

Surgical morbidity substudySurgical morbidity substudy

GI perforations. Incidence and outcomesGI perforations. Incidence and outcomes Wound healing in patients undergoing major Wound healing in patients undergoing major

surgery less than 28 days prior to starting surgery less than 28 days prior to starting bevacizumab.bevacizumab.

Wound healing in patients undergoing any Wound healing in patients undergoing any surgery during the administration of surgery during the administration of bevacizumab.bevacizumab.

Wound healing in patients undergoing any Wound healing in patients undergoing any surgery during 28 days after the administration surgery during 28 days after the administration of bevacizumab.of bevacizumab.

PerforationPerforation

Tumour at site of perforationTumour at site of perforationGI obstructionGI obstructionAbdominal CarcinomatosisAbdominal Carcinomatosis Intraabdominal AbscessIntraabdominal AbscessAcute DiverticulitisAcute DiverticulitisOther FindingsOther Findings

Grading of PerforationGrading of Perforation

Grade 1: Asymptomatic X-Ray findings Grade 1: Asymptomatic X-Ray findings only.only.

Grade 2 : Medical intervention indicated, Grade 2 : Medical intervention indicated, I/V fluids for< 24 hours.I/V fluids for< 24 hours.

Grade 3: IV fluids, tube feeding, TPN, Grade 3: IV fluids, tube feeding, TPN, operative interventionoperative intervention

Grade 4 : Life threatening ComplicationsGrade 4 : Life threatening ComplicationsGrade 5 : DeathGrade 5 : Death

Wound HealingWound Healing

Wound InfectionWound InfectionWound DehiscenceWound DehiscenceAbscess formationAbscess formationAnastomotic leakage (Radiolgical/Clinical)Anastomotic leakage (Radiolgical/Clinical)Return to TheatreReturn to TheatreLength of Stay (ICU/Hospital)Length of Stay (ICU/Hospital)DeathDeath