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1304 Technique of Intraperitoneal Chemotherapy: Normothermic and Hyperthermic
perfusate to all areas of the PC (48). It also allows assist distribution this can be achieved by insertion of a
easier fluid collection for pharmacodynamic studies, hand-assist port (56).
tissue collection for chemotherapy uptake analysis
and continued surgery with removal of tumor nodules The major advantage of the laparoscopic method is
during the perfusion. Although a major disadvantage the reduced wound morbidity and earlier recovery for
of the open method would appear to be the potential the patient (54, 55).
for environmental contamination on investigation this
has never been proven. A further proposed deficiency is Morbidity and mortality of HIPEC
that due to heat loss through the open wound it may be
more difficult to maintain an even temperature in the PC. Morbidity or mortality specifically due to HIPEC is
There are reports of having to heat the inflow temperature difficult to dissociate from that associated with the often
above the required level to maintain the temperature in extensive CRS associated with it.
the PC and this would be concerning for the risk of ‘hot
spots’ causing local tissue damage resulting in impaired In a report of 141 patients in the HYPERO registry
wound and anastomotic healing (49). The bottom line is undergoing HIPEC at all natural history time points in
that no study has ever shown a difference in morbidity EOC the mortality rate was 2.1% (57). In a systematic
or mortality with either technique and the risk of review (2009) of 19 studies involving 895 patients with
contamination is minimal. EOC, the overall mortality rate for CRS and HIPEC was
Laparoscopic Delivery of HIPEC variably reported between 0 and 10% (58). With regard
For some patients HIPEC can be delivered in a minimally to morbidity, the complication frequency by grade
invasive fashion (Figure 8). This may be the case when was reported as: Grade I (no intervention required for
disease can be resected laparoscopically or when HIPEC resolution) 6-70%, Grade II (medical treatments required
is to be given for consolidation following a complete for resolution) 3-50%, Grade III (invasive interventions
clinical response to frontline therapy when the only including radiological required for resolution) 0-40% and
surgical procedures necessary are adhesiolysis and the Grade IV (required urgent definitive intervention such as
taking of biopsies. This approach was first reported by returning to the operating room or intensive care unit for
Chang et al (50) and is now widely utilized (51-55). resolution) 0-15%. Severe complications included ileus,
anastomotic leakage, bleeding, pleural effusion, wound
After initial laparoscopic assessment and surgery, IT and other infections, fistula and thrombocytopenia.
and OT are placed through incisions/tracks made by the
10-12 mm laparoscopy ports. The laparoscopic port is When HIPEC was used in recurrent disease in 256
removed and the end of the tubing (32F) is passed into the patients at the time of CRS, complications included
PC with the aid of a forceps. Under laparoscopic camera hematologic 4.3%, creatinemia 3.9%, wound infection
guidance the tip is grasped using a laparascopic grasper 4.3%, anastomotic leak 1.6%, bowel perforation 2.3%,
and placed in the appropriate part of the abdomen. peritonitis 0.8% and abscess formation 1.2% (21). The
The skin edges and tubing are secured with interrupted rate of anastomotic leak in the absence of a diverting
sutures such as 0 polyglactin 910 (Vicryl®, Ethicon Inc, stoma remains unknown. Spontaneous intestinal
Somerville, NJ). If the surgeon wishes to use a hand to perforations do occur and may reflect the effect of heated
chemotherapy on bowel which has been traumatized,
Figure 8. HIPEC Laparoscopic technique particularly during enterolysis.
From (40) with kind permission of the publisher and Dr Jesus Es-
quivel, St Agnes Hospital, Baltimore, MD, USA A majority of recent reviews and studies, including
a large French multi-institutional observational study
on 566 patients, report a post-operative mortality
rate of 0-5% and major (Grade III/IV) morbidity of
approximately 40% (30, 59-61). In a recent systematic
review (2015), the pooled median 30-day post-HIPEC
mortality rate was 1.8%, major (Grade III/IV) morbidity
rates for primary and recurrent EOC were 31.3% and
26.2% and minor (Grade I/II) morbidity rates were 40%
and 27.5% respectively (29). Peritoneal Carcinomatosis
Index (PCI) score > 12 and intestinal resection were
independent prognostic factors for grade III/IV morbidity
after CRS and HIPEC in a Spanish observational study
(63). Majority of the ongoing clinical trials have toxicity
and morbidity as endpoints (Table 6) as well QOL and
survivorship after HIPEC (NCT01126346–HOPE study).
Whatever the additional morbidity of HIPEC alone, it
is likely to be low when matched against the CRS often
performed alongside and may be reduced by careful
patient selection and experience.
