Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Now and the Future



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Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Now and the Future Mazin Al-kasspooles, MD Associate Professor of Surgery Division of Surgical Oncology Director, Regional Therapy Program University of Kansas Medical Center AmSECT Meeting Tampa, FL April 14, 2015

Peritoneal Surface Malignancy Definition Cancerous cells that have seeded outside the primary site of cancer and formed tumors on: Peritoneal surfaces Inside of the abdominal and pelvic walls Surfaces of the bowel, including the mesentery Omentum On surfaces of other organs: Liver, Spleen, Gallbladder, Bladder, Uterus, Ovaries **Different than cancer that has spread by lymphatics or the blood stream. Aggressive Disease Process Historically considered a highly terminal process with very few patients surviving over 6 months, even when treated with systemic therapy

Peritoneal Surface Malignancy

Peritoneal Surface Malignancy

Peritoneal Surface Malignancy

Peritoneal Surface Malignancy

Peritoneal Surface Malignancy

Pathophysiology of Peritoneal Malignancy Mechanisms of Peritoneal Seeding Free intraperitoneal seeding from serosal invasion Spontaneous or iatrogenic tumor perforation through serosa Late site of metastases in advanced cases Via bloodstream or lymphatics Loss of blood or tissue fluid containing tumor cells into the surgical field Veins Lymphatics

Appendiceal Neoplasm Prior to Rupture

Pathophysiology of Peritoneal Malignancy Patterns of dissemination Gutters of the abdomen and pelvis GRAVITY! Areas that are relatively immobile Often see sparing of the small bowel Survival in micro-environment Evade immune system Develop blood supply Growth Using bodies own inflammatory/recovery process Angiogenesis Self-sustaining Peritoneal tumors block absorption of fluid ascites Ascites provides fertile environment for tumor progression

Rationale for Intraperitoneal Chemotherapy Systemic Chemotherapy relatively ineffective for this disease process Paradoxically, surgery alone favors peritoneal dissemination Tumor spillage Tissue trauma Environment conducive to tumor implantation and growth

Hyperthermic Intraperitoneal Chemotherapy Rationale Direct Effects of Hyperthermia

Hyperthermic Intraperitoneal Chemotherapy Rationale Advantages of Adding Hyperthermia to Chemotherapy

Indication for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) Perforated Appendiceal Cancer Standard of care for 3 decades Classic jelly-belly (pseudomyxoma peritonei) Approximately 1000 cases per year and stable Primary Peritoneal Mesothelioma Mesothelioma that originates from inside the abdomen Standard of care for 3 decades Approximately 500 cases per year and stable

Indication for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) **Abdominal Recurrence of Colorectal Cancer (Carcinomatosis) CRS-HIPEC utilized in past 10 years Data shows that survival is doubled with complete cytoreduction Use for this disease rapidly increasing Approximately 20,000 cases per year and increasing **Recurrent Ovarian Cancer CRS-HIPEC utilized in past 3 years Data shows that survival is doubled with complete cytoreduction Use for this disease process rapidly increasing Approximately 20,000 cases per year and increasing

Volume at KUMC 50 45 40 35 30 25 20 15 10 5 0 CRS-HIPEC Limb Perfusion Total Treated 2011 2012 2013 2014

Volume at the University of Kansas Medical Center Total Evaluated in Operating Room for HIPEC 60 61 16 22 2011 2012 2013 2014 Total Evaluated in Operating Room for HIPEC

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Insertion of cannulas and temp. probes Temporary close Connect circuit to Pump Circulate and heat for 30 to 90 minutes (depends on drug) at 41-43 degrees Celsius Open and irrigate Reconstructive surgery & close

Future Trends Almost exponential rise in the CRS-HIPEC procedure Indications continue to broaden Increased awareness of potential candidates e.g. Education of medical oncologists and general surgeons Increased number of candidates for given disease site Older population Patients living longer with advanced cancer Discovery of more effective drug combinations to be used in perfusate Discovery of new novel agents to be used in perfusate Better delivery mechanisms Use of nanoparticles that can linger in the abdominal cavity after CRS- HIPEC Improved patient selection Not all candidates benefit from the procedure Preoperative clinical information (scoring system) Molecular markers

Opportunities at KUMC Geographical Considerations