Rule of six for CRS and HIPEC : An Institutional Experience

Introduction –

We, on the basis of our experience of last 7 years at a tertiary care centre, tried to develop a standard protocol as ‘RULE OF SIX IN HIPEC’ for the better understanding and management of this challenging procedure. This rule may help for the better outcomes of HIPEC procedures, practiced as six indications, six rationale, six criteria of patient selection, six contraindications, six advice before HIPEC, Six steps of checking before CRS, Six assessment for NACT, Six steps of surgery, six mechanism of action, six important complications, six advice in discharge, six important points to be clarified still. The observational data is based on the analysis of the surgical procedure and its outcome in 150 patients.

1. Diseases to be considered under PSM

Worldwide Six common indications for CRS & HIPEC. But, in carcinoma appendix with pseudomyxoma peritonei and mesothelioma CRS and HIPEC has been the standard of care. These malignancies are enumerated as follows.[1]

• Carcinoma appendix with Pseudomyxoma peritonei
• Mesothelioma
• III. Colorectal cancer
• Ovarian cancer
• Gastric Cancer with Peritoneal dissemination only
• Peritoneal Sarcomatosis

2. Rationale:

Literature suggests six reasons to be considered.

• the disease is confined to the peritoneal cavity for a long time
• Even in recurrent cases, disease remain confine to peritoneal cavity only.
• Intra peritoneal administration of chemotherapy results in high peritoneal to plasma ratios for peak concentration of chemotherapeutic drugs.
• The higher peritoneal concentration improves penetration of cytotoxic agent in tumor microenvironment.
• Less than 2 to 3 mm deposits have significantly higher chemotherapeutic drug exposure from IP administrations as compared to IV.
• Avascular tumours are exposed to higher drug concentration

3. Patient Selection:

Six Criteria to be followed :

• Good performance status ECOG1 and ECOG 2 with optimisation.
• Mentally and physically fit for extensive surgery.
• Clinically, radio logically and biochemically the disease is low burden and resectable.
• No Haematogenous and extra abdominal metastasis
• Good renal function.
• Age < 65 years with PFT (FEV1 > 1-1.5lts), non-smoker with complete blood counts, kidney function rests and liver function tests within normal limit.

4. Contraindications:

• Poor performance status, i.e; ECOG ≥ 3
• Patients is not willing for extensive surgery.
• Signs and symptoms of active peritonitis and sepsis.
• Clinically and radiologically high burden disease involving porta, root of mesentry , diffuse serosal deposits, disease burden not amenable for optimal cytoreduction.
• Compromised liver, renal and respiratory function.
• Age ˃ 70 with cardiovascular compromise.

5. Preoperative Therapy:

Indications for NACT before CRS + HIPEC, when;

• Imaging suggestive of high tumor burden where upfront optimal CRS is not feasible.
• Tumor ≥3 cm around porta hepatis or around root of mesentry.
• Intra hepatic metastasis or extra abdominal disseminated disease.
• Where bowel resection is required more than 1.5 m due to extensive serosal or intra luminal involvement.
• Possibilty of ≥ 2 small bowel anastomosis after CRS.
• Extensive retroperitoneal lymph nodes.

6. Optimisation: P

Atients to be optimised preoperatively by Six ways

• High protein diet
• Maintenance of hygiene.
• Regular ½ hour to 1 hour mild to moderate physical exercise.
• Incentive spirometry 200 times/day.
• Haematinics to optimise haemoglobin
• Adequate hydration 2.5 – 3 litres of liquids inclusive of water per day to keep the renal function normal.

7. Intraoperative Assessment

Of disease

• Overall disease burden at primary site
• Involvement of bowel bladder and it extend.
• Root of mesentery and small bowel involvement.
• Exclude the liver and spleen involvement
• Sub diaphragmatic involvement of diaphragm.
• Exclude involvement of porta hepatis and SM vessels.
• Surgical Technique for Peritonectomy: Six basic steps to be followed:
• Proper exposure of abdomen parietal peritonectomy
• Greater Omentectomy and Splenectomy if required.
• Left upper quadrant peritonectomy
• Right upper quadrant peritonectomy and capsule of liver and sub diaphragmatic space.
• Lessor omentectomy, removal of omental bursa with cholecystectomy.
• Pelvic peritonectomy the peritoneum below the pelvic brim including pouch of Douglus and bladder peritoneum.

8. Just before HIPEC

Check list to be verified

• Secure haemostatis – most important
• Complete cytoreduction( CC score)
• Vitals stability
• Drug dose as per BSA or NS/L
• Placement of inflow outflow catheter and temp probe. Inflow catheter should be away from anastomotic site/sites.
• Drug to be delivered only when inflow outflow temp would be in between 41- 43 C.

9. Mechanisms for HIPEC

Six mechanisms of Action of HIPEC [5]

• Heat increases chemo drugs penetration into tissue up to 5-7 mm.
• Heat itself has anti tumour effects and it increases cyto-toxicity.
• Intra operative drugs and heat (41-42 C) distributed manually to all surfaces in abdominal cavity.
• Plasma peritoneal barrier limits systemic absorption of drugs and thereby less systemic adverse effect
• Hyperthermia increases platinum sensitivity.
• The time elapses during HIPEC (30-90 minutes) allows removal of small cancer nodules from surfaces including bowel serosa and mesentery.

10. Morbidity and Mortality

Six common morbidities

• Paralytic ileus with nausea vomiting – most common
• Lymphocele formation
• Anastomotic leak
• Surgical site infection with wound dehiscence
• Derangement of Renal function and RT I
• Entero-cutaneous fistula (Mortality worldwide 0-10%)

Dr. Seema Singh
Consultant – Surgical Oncology
RGCIRC, Niti Bagh, South Delhi