A patient being treated using Cytoreductive surgery and HIPEC at a Dr. Sanket Mehta clinic A patient being treated using Cytoreductive surgery and HIPEC at a Dr. Sanket Mehta clinic

Cytoreductive
Surgery and
HIPEC

What is CRS and HIPEC

In essence, CRSand HIPEC are new treatment techniques developed for the cure of Peritoneal surface malignancies.

Peritoneal surface malignancies are tumours that either arise from the peritoneum itself or that spread predominantly to and along the peritoneal surface.

Peritoneum is a membrane that lines the inner surface of the abdominal cavity and envelopes the intra-abdominal organs and viscera. The peritoneum is made of two parts, the visceral and parietal peritoneum. The visceral peritoneum covers the internal organs and makes up most of the outer layer of the intestinal tract while the parietal peritoneum covers the abdominal cavity.

Peritoneal surface malignancies are basically diseases that tend to spread along the peritoneal surface by a phenomenon called as “Redistribution”. The free cancer cells are released in the peritoneal cavity and are carried in the peritoneal fluid. These cells settle down in the areas of stasis and absorption of peritoneal fluid. Usually, there is a latent period during which they are confined to the peritoneal cavity and amenable to CRS and HIPEC. Once the disease starts spreading outside the peritoneal cavity, the chances of offeringCRS and HIPEC decrease as the efficacy of the treatment decreases.

These kinds of tumours present a rather prickly, therapeutic challenge since the naturally existing blood-peritoneal barrier (a physiological barrier that separates the blood stream and the peritoneal cavity) physically prevents the chemotherapy administered intra-venously from entering the peritoneal cavity in adequate concentrations to be effective at all in eradicating the disease. Further, the disease has a tendency to spread by the phenomenon of “Redistribution” settling down in areas of stasis and where peritoneal fluid has been reabsorbed. Finally, in patients who are already operated upon, the post-operative adhesions serve as sanctuaries for carcinomatosis (cancerous) cells since chemotherapy cannot reach those areas because of the poor blood-supply post-surgery.

Rationale

To overcome the above-mentioned challenges, a treatment protocol comprising of a combination of chemotherapy and surgery has been developed in the recent years after several painstaking and systematic experimental and clinical studies. It takes place in 2 stages.

  • Cyto-Reductive Surgery
  • Hyperthermic Intra-Peritoneal Chemotheraphy

The Cyto-reductive “Maximal Effort Surgery” is a procedure that involves systematic, laborious and thorough physical removal of all visible tumour tissue. This, theoretically, reduces a stage IV disease to an RO (no residual tumor status) status with no macroscopic or visible disease. The microscopic disease that may be left behind after such a long surgery is then further eradicated by the HIPEC (Hyperthermic Intra-peritoneal Chemotherapy). It is the combination of both these modalities that makes this treatment highly effective in the treatment of peritoneal surface malignancies. Now, although this sort of treatment is still advanced and therefore, a novelty, fortunately, the required infrastructure, equipment and more importantly the expertise are all now available for the first time in the country in Mumbai. Dr. Sanket Mehta, who has trained in France at one of the pioneering centres for the treatment of peritoneal surface malignancies and colorectal and hepatic diseases, started the first Peritoneal surface malignancy program in Mumbai with his clinic.

Diseases Treated by CRS and HIPEC

The diseases treatable by CRS and HIPEC are called as Peritoneal Surface Malignancies.

These include:

  • Pseudomyxomaperitonei
  • Appendiceal cancers
  • Peritoneal mesothelioma
  • Colorectal cancers with peritoneal metastases (colorectal carcinomatosis)
  • Ovarian cancer with peritoneal metastases (especially recurrent or residual platinum-sensitive ovarian cancers)
  • Primary peritoneal carcinoma
  • Desmoplastic small round cell tumors
  • Select cases of endometrial cancers with peritoneal metastases (cancer of the endometrium of the uterus that has spread to the peritoneum), gastric or stomach cancer with peritoneal metastases, and other rarer peritoneal surface malignancies.

HIPEC procedures

HIPEC procedure used to cirulate a heated sterile solution, containing a chemotherauptic agent throughout the peritonial cavity

During the HIPEC procedure, the surgeon will continuously circulate a heated sterile solution - containing a chemotherapeutic agent - throughout the peritoneal cavity, for a maximum of two hours. The HIPECprocedure is designed to attempt to kill any remaining cancer cells. The procedure also improves drug absorption and effect with minimal exposure to the rest of the body. In this way, the normal side effects of chemotherapy can be avoided.

results

Peritoneal malignancies traditionally have had a poor prognosis with virtually no chance of cure and at best marginal improvement in survival results with palliative chemotherapy. These include diseases likePseudomyxomas, Mesotheliomas, Papillary cystic and Mucinous tumors, Peritoneal dissemination of colorectal, gastric and Ovarian tumors and other gastro-intestinal tumors.

In the last decade, a new treatment strategy has been developed to tackle these types of diseases, which involves Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). This is a rapidly growing field with the indications expanding rapidly and results that prove beyond doubt the effectiveness of the treatment. For instance,

  • For Pseudomyxomas, the traditional treatment results in a 5-year survival of upto 50% at best with a poor quality of life and multiple surgeries. CRS and HIPEC is already established as the treatment of choice with a recent multicentric study showing a 10-year survival of upto 70%.
  • For diffuse Malignant Peritoneal Mesotheliomas, the median survival with traditional treatment strategies is at best 1 year; however, with CRS and HIPEC the median survival in recent series has approached 5 years with more than 50% 5-year survival rates.
  • For Peritoneal Carcinomatosis of Colorectal cancer origin, there is a randomized controlled trial and several well-conducted retrospective and prospective studies providing overwhelming evidence in support of CRS and HIPEC. In a recent bicentricfrench series (in which Dr. Sanket Mehta was a co-author – presented in ASCO GI 2011 and accepted for publication in the Annals of Surgery) of 148 patients, the median survival approaches 42 months, which is overwhelmingly favorable compared to the results of traditional treatment strategy yielding a median survival of 9-14 months at best.
  • Similar dramatic results are obtained in recurrent Platinum-sensitive Ovarian Carcinomas, Gastric Carcinoma with Peritoneal Carcinomatosis and other rare Peritoneal Malignancies.
  • Comprehensive quality of life studies and cost-effectiveness studies have also shown results in favor ofCRS+HIPEC.
  • In the last decade, the number of centres offering this kind of treatment has grown from a handful of French and American centres to more than 35 centres worldwide. Regrettably, in spite of India being one of the most populous countries, there was not a single centre or a single trained team offering CRS+HIPECtreatment.

    With the incidence rates of 2/million/year for Pseudomyxomas and Mesotheliomas, 11-14% of all Colorectal tumors that develop exclusive Peritoneal Carcinomatosis, upto 20% of all ovarian tumors that recur and approximately 20% of all Gastric cancers that are operable but with Peritoneal Metastasis, a city like Mumbai alone has more than 1000 patients that could benefit from this type of treatment.