Traditionally peritoneal surface malignancies (PSM) were considered as advanced and incurable cancers and the management appraoch was generally palliative. However, during the last two decades, with the advances made in the field of CRS and HIPEC, peritoneal surface dissemination of abdominal malignancies is increasingly being recognised as a regional disease amenable to potential cure in a subset of patients. One of the major breakthroughs that helped in mainstreaming CRS & HIPEC include surgical standardization of total peritonectomy by Paul H. Sugarbaker in 1995[6, 8]. Parallel advancements in the field of HIPEC resulted in increasing utilization of CRS & HIPEC as an effective combination therapy for PSM by a number of centres [2]. Last decade has witnessed a spurt in publication of literature pertaining to CRS and HIPEC mainly from HIC. Due to the complexity of treatment, cost factors and associated higher morbidity and mortality very few centres from LMIC have ventured in to CRS and HIPEC programs despite having a significant volume of patients with PSM. There is a need to share the experience of CRS and HIPEC from resource constrained settings to assess the feasibility, safety and efficacy.
We present our experience of first 155 cases of CRS and HIPEC perfomed at a tertiary care cancer centre in India, a lower-middle income country.
CRS and HIPEC is a time and resource intensive intervention and for initiation of long term viable CRS & HIPEC program good healthcare infrastructure and a multidisciplinary team appraoch is essential. Other important issue is optimal patient selection for CRS & HIPEC. These procedures should only be offered to group of patients who are likely to benefit to optimize resource utilization. Two factors need to be considered while selecting patients for CRS and HIPEC. First is the disease type and second is the extent and volume of peritoneal spread. Based on current literature pseudomyxoma peritonei, mesothelioma, peritoneal metastases of tumors of appendicular and colorectal origin and ovarian cancers have shown benefit with CRS and HIPEC. Volume and extent of peritonel spread can be assessed by CT-PCI score and feasibility of optimal cytoreduction plays a crucial role in decision making for CRS and HIPEC. Performance status of the patient and presence or absence of co-morbidities is also a key factor in patient selection process.
We followed a stringent patient selection criteria in the current study.
Two thirds of the patients had no co-morbidity and the remaining had co-existing diseases like diabetes mellitus, hypertension, hythothyroidism which were well controlled. A conscious decision was also taken to exclude patients with aggressive histologies and very high tumor burden.
Spectrum of patients undergoing CRS and HIPEC varies in different studies. Factors which can influence the disease spectrum include type of surgical specialty and referral patterns. Most of the studies from the west related to CRS & HIPEC have a preponderence of tumors of gastro-intestinal tract origin. In a study published by Levine et al comprising 1000 patients, 47.2% of the tumors were of appendiceal origin, 24.8% colorectal origin and only 6.9% were that of ovarian origin. [9–11]. In the current study more than half of the patients had tumors of ovarian origin. Peritoneal metastases of colorectal origin and pseudomyxoma peritonei comprised one fourth of the volume. These trends are likely to change over a time period due to referral patterns and revision of guidelines based on results from ongoing randomized studies.
The average peritoneal carcinomatosis index (PCI) in our series was 9.3, lower than that reported in other contemporary series where mean PCI ranged from 11 to 16 [9, 12–14]. Perhaps, this is because of a stringent selection criteria used and preponderance of cases of carcinoma ovary receiving prior chemotherapy resulting in down staging and low PCI. The mean PCI for non-ovarian cancer patients was 11.1 in our series.
In view of the complexity and variations in protocols reported in literature, every institution planning to start CRS and HIPEC programs should have standard and uniform protocols pertaining to patient selection, prehabilitation, surgical technique, HIPEC methods, anesthesia and ICU care for consistent outcomes. Meticulous documentation of patient and treatment details, preferbly in a structured electronic format is important, which helps in performing audits for learning and facilitates analysis of quality data for outcomes .
As far as surgical procedures are concerned, preliminary meticulous exploration of abdomen to document PCI and assessment of feasibility of optimal CRS is a very critical step which will help in early decision making. We suggest a senior and experienced surgeon be involved in this part of the procedure. It is recommended to have a team of surgeons well versed with intricacies of CRS and they can work as teams to avoid fatigue and errors. At our institution two experienced surgeons performed majority of the procedures during the intial phase and susequently trainees were also allowed to perform simple peritonectomies under supervision. The main surgical goal is to achive an optimal CRS status, balancing risk versus benefit. In the current study, 21.1% had total peritonectomy and the remaining had partial disease specific peritonectomy. Approximately one fourth of patients required multi visceral resection. For the HIPEC phase of surgery, adherence to safety protocols using safe and efficacious cytotoxic agents is key to success. Dosages of prior chemotherapy a patient has received should always be kept in mind while deciding the intraperitoenal chemotherapy dose so as to avoid toxicity.
Most of the initial studies reported a very high morbidity and mortality with CRS and HIPEC [15, 16]. However, with increasing experience contemporary studies are reporting an acceptable rate of morbidity and mortality [10, 17, 18]. In the current study, peri-operative morbidity occurred in 28.0% of patients. The most common morbidities encountered were deep vein thrombosis, subacute intestinal obstruction, sepsis and burst abdomen. Morbidity of the current study is comparable to the morbidity reported in recent studies. Overall mortality in our experience was 3.5% which was acceptable in comparison to mortalities reported in recent studies reporting a mortality rate ranging from 2 to 8.6%.