Commentary (Petrelli): Managing the Peritoneal Surface Component of Gastrointestinal Cancer

Dr. Paul H. Sugarbaker has spent most of his surgical oncology career researching and treating patients with peritoneal surface malignancies. His participation in the treatment of 385 patients with appendiceal malignancy over a 15- year period is probably the largest such experience ever reported.[1] Dr. Sugarbaker has demonstrated that in patients with peritoneal carcinomatosis from gastrointestinal malignancies, the best treatment results are associated with mucinous epithelial malignancy of the appendix. Intracoelomic Cancer Dissemination
Dr. Sugarbaker's research has led him to describe the profound impact that intraperitoneal fluid has on the patterns of cancerous dissemination within the peritoneal cavity.[2] Based on observations collected from his experience in reoperative surgical procedures, he has described and contrasted three important mechanisms of intracoelomic cancer dissemination. These patterns include (1) gastrointestinal cancer implantation, which occurs in a random fashion immediately adjacent to the primary neoplasm that has penetrated the serosal surface; (2) the development of ascitic fluid or mucus by cancers that subsequently cause the characteristic redistributed pattern of implants; and (3) intraperitoneal cancer dissemination caused by surgical dissection, which is referred to as tumor cell entrapment. Surgeon's Skill
Early in my career, I was severely critical of Dr. Sugarbaker's reports about the management of peritoneal surface malignancies. This criticism was based on the fact that his data were not reproducible by other investigators. However, I am now convinced that this criticism was unwarranted. A surgeon treating patients with peritoneal surface gastrointestinal cancer must master the technical skills required for the completion of peritonectomy, and Dr. Sugarbaker has emphasized that this procedure is necessary to remove all visible cancer in an attempt to leave the patient with only microscopic residual disease. I believe that the inability to reproduce Dr. Sugarbaker's results has been in some part due to the failure to perform a complete peritonectomy. This meticulous procedure must be mastered to achieve the same results as Dr. Sugarbaker. Just mastering the technical aspects is not enough. Surgeons must also understand the dissemination patterns of gastrointestinal cancer spread to peritoneal surfaces in order to develop successful treatment programs. As Dr. Sugarbaker states in part 1 of his article, unless all sites are inspected and all foci of cancerous implants removed, "patients will be left with gross disease and a poor long-term outcome." Understanding the natural history has proven to be helpful in understanding the potential deadly nature of peritoneal carcinomatosis. Unfortunately, peritoneal carcinomatosis does not equate with a good quality of dying[3]; large and small bowel obstruction with associated bowel perforation does not lead to an easy death. Multidisciplinary Approach
Although in the past the diagnosis of peritoneal carcinomatosis from intra- abdominal gastrointestinal tumors carried a fatal prognosis, recent reports have differed.[4,5] These reports have demonstrated that the treatment of peritoneal carcinomatosis is a particular area in oncology where progress needs to continue. It is sometimes difficult for readers to distinguish between the standard of care and investigational treatments. One major advance stemming from Dr. Sugarbaker's experience is that the standard of care for the treatment of peritoneal surface malignancies must involve a multidisciplinary team approach. Without question, this is best illustrated by a visit to Dr. Sugarbaker's multidisciplinary unit at the Washington Cancer Institute in Washington, DC. Over the years, he has assembled a team of enterostomal therapists, social workers, nutritionists, surgical and medical oncologists, and other paramedical personnel who make his program a success. A multidisciplinary team approach is mandatory for any institution that wants to initiate a treatment program for patients with peritoneal surface malignancies. Areas for Further Research
Although there is increasing evidence documenting some degree of efficacy for such treatment,[4,5] several issues still need to be addressed. Areas in which there are a wide range of research opportunities include (1) the efficacy and safety of open vs closed peritoneal chemotherapy perfusion, (2) the proper choice of chemotherapeutic options and perfusion techniques, (3) in intraperitoneal hyperthermic perfusion, the amount of heat necessary for optimal cell kill and acceptable morbidity and mortality, (4) simpler and less costly perfusion apparatus, (5) quantitative prognostic indicators that will allow proper selection of patients for therapy (this has come a long way, as described by Dr. Sugarbaker), and (6) better definition of the role of additional systemic therapy in combination with intraperitoneal chemotherapy. Dr. Sugarbaker notes that several authors have tested the combination of cytoreductive surgery and hyperthermic intraperitoneal intraoperative chemotherapy. However, readers must be aware that there are considerable differences between series regarding both tumor-related issues (such as tumor histology and tumor stage at laparotomy) and technical features (as described above). It is this heterogeneity among series and the absence of well-designed phase III randomized trials that make many investigators pessimistic about this approach to peritoneal carcinomatosis. Another area that sometimes frustrates efforts to interpret the literature concerning peritoneal surface malignancies is the issue of quality of life. Recent results by McQuellon and associates from the Comprehensive Cancer Center of Wake Forest University[ 5] demonstrated long-term survival with good quality of life for selected patients with peritoneal carcinomatosis after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. Such results are important if we are to make progress in this area of cancer research. Conclusions
In my opinion, this review by Dr. Sugarbaker is outstanding and should be mandatory reading for physicians involved in the treatment of patients with peritoneal carcinomatosis. With a multidisciplinary team approach and qualified surgeons, more programs will become available across the United States. Such an effort has been undertaken in Delaware, where a collaboration between the Tunnell Cancer Center at Beebe Hospital and the Helen F. Graham Cancer Center at Christiana Care has resulted in multidisciplinary teams and a program for the treatment of peritoneal surface malignancies. Nevertheless, a definitive assessment of the management value of cytoreductive surgery and intraperitoneal chemotherapy will be possible only if the technique is standardized and phase III clinical trials are undertaken.