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Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in patients with limited Pseudomyxoma Peritonei of appendiceal origin

Jesus Esquivel MD and Andrew Averbach MD Department of Surgical Oncology, St Agnes Hospital, Baltimore, Maryland, USA

Introduction Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have become standard of practice in patients with Pseudomyxoma Peritonei. The open procedure has been associated with high Grade III and IV morbidity and prolonged hospitalization. In addition, we are starting to see that many patients with PMP are being referred to a Peritoneal Surface Malignancy center as soon as they are diagnosed and not after 3 or 4 abdominal procedures as we used to see in the late 90's. Furthermore, the number of patients that are diagnosed after a laparoscopic appendectomy is on the rise as well. What to do in this particular group of patients is still a matter of debate, with half of the cytoreductive surgeons recommending a watch and wait approach and the other half recommending cytoreductive surgery and HIPEC. One of the problems with the watch and wait approach is that it generates anxiety in some patients and that the follow up requires numerous CT scans. This of course exposes the patient to increasing doses of radiation. MRI is becoming a very useful tool to evaluate the abdomen and pelvis for additional mucinous implants and hopefully will help to reduce the amount of radiation exposure. The problem with the "cookie-cutter" approach of treating every patient with PMP with a very large incision in order to rule out the presence of any residual disease is the fact that many of these patients are going to have very limited peritoneal disease. Therefore this approach represents an opportunity to improve patient care. This is the

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year 2010, where reports on laparoscopic surgery for cancer patients have been published in just about every organ in the abdomen. Prospective randomized trials have shown that there is no difference in port site and wound recurrence, no difference in distant recurrence and no difference in survival in patients undergoing laparoscopic surgery for primary colon cancer, in fact, some of these studies show a better outcome in those having laparoscopic surgery (1).

For these reasons, and understanding that laparoscopic surgery is NOT a different surgery but rather just a different approach, our group decided to evaluate the role of laparoscopic cytoreductive surgery and HIPEC in patients with limited peritoneal dissemination. The results with the first 14 patients that included a variety of peritoneal surface malignancies look very promising and are currently in press in the Annals of Surgery (2). The purpose of this manuscript is to report our continued experience from this protocol in patients with Pseudomyxoma Peritonei of appendiceal origin, also referred as Low-grade mucinous carcinoma peritonei (L-MCP) or DPAM, Disseminated Peritoneal

AdenoMucinosis.

Materials and Methods Patients with an established diagnosis of Pseudomyxoma Peritonei and no gross evidence of carcinomatosis on the CT scan were enrolled in a research clinical protocol. Figure 1. In short, these patients would undergo a diagnostic laparoscopy and if the Peritoneal Cancer Index (PCI) was 10 or less, the cytoreductive surgery and HIPEC would continue via the laparoscopic route. If the PCI was greater than 10 or the procedure could not be

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carried out laparoscopically, then the operation would be converted to the open approach. The protocol was approved by our Institutional Review Board (IRB) and all the patients signed an informed consent. We aimed to assess the feasibility, safety and outcome of this procedure. Postoperative complications were reported according to the National Cancer Institute Common Toxicity Criteria. These criteria report Grade 1 morbidity as an abnormal finding either on a laboratory value or an imaging study but that has no clinical consequences and therefore merits no therapy. Grade 2 includes an abnormal finding that requires treatment with a pharmacological agent (like given a medication for high blood pressure). Grade 3 includes a post-operative complication that requires a "physical" intervention like a percutaneous drainage of an abscess and Grade 4 represents a complication that requires another surgical intervention.

Results From December 2008 to December 2010, 12 patients with the diagnosis of Pseudomyxoma Peritonei of appendiceal origin were enrolled into the protocol. Mean age was 52. All patients had previous surgeries. Fifty percent had a previous

laparoscopic procedure and 50% a previous open procedure. All 12 patients had a complete cytoreduction and HIPEC; 11 (91%) laparoscopically and 1 (9%) was converted to an open procedure because we thought that the disease present in the previous anastomosis was going to be too difficult to be removed laparoscopically. This case is the only patient with PMP that was converted to an open procedure and it happened 21 months ago; since then, the following 8 cases have been completed laparoscopically. The mean PCI was 5 and mean operative time was 5 hours. Twenty-

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five percent required a bowel resection and 25% required a limited peritonectomy. Grade 3 morbidity was Zero and one patient (9%) in the laparoscopy group experienced a Grade 4 complication, needing a reoperation for an internal hernia; this re-operation was also completed laparoscopically and the patient went home 14 days after the first surgery. There were no operative deaths. Mean length of hospital stay was 6 days. As of today, December 15, 2010, all patients are alive and well, with no evidence of recurrence. It is important to note that the follow up ranges from 24 months to less than one month. Table 1. Our first laparoscopic procedure was on a patient with peritoneal mesothelioma (3). This patients is now 31 months after the laparoscopic cytoreduction and HIPEC and is currently free of disease.

Conclusion This initial investigative stage demonstrates that laparoscopic cytoreductive surgery and HIPEC in patients with limited peritoneal dissemination from Pseudomyxoma Peritonei of appendiceal origin is feasible and safe and therefore should be added to the armamentarium of treatment options for this group of patients. It is important to

emphasize that this approach needs longer follow up and as any new therapeutic approach, it should be done under the auspices of a clinical research protocol. In order to decrease the learning curve, the surgical team should include not only a cytoreductive surgeon but a surgeon that does minimally invasive surgeries on a routine basis. As mentioned before, our only conversion was 21 months ago, this represented our 4th case and the patient that needed the re-operation was our second patient. We have learned since then that the minimally invasive nature of early Pseudomyxoma Peritonei is

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amenable to a minimally invasive management and treatment.

Currently, our

laparoscopic patients do not have a nasogastric tube, do not go to the Intensive Care Unit (ICU) and have no intra-abdominal drains (JPs).

References

1. Angst E, Hiatt JR, Gloor B, Reber HA, Hines OJ. Laparoscopic surgery for cancer: a systematic review and a way forward. J Am Coll Surg. 2010 Sep;211(3):412-23.

2. Esquivel J, Averbach A, and Chua T. Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Patients with Limited Peritoneal Surface Malignancies: Initial Feasibility and Safety Results. Annals of Surgery. (in press)

3. Esquivel J and Averbach A Combined Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a patient with peritoneal mesothelioma: First Case Report. J Laparoendosc Adv Surg Tech; 19 (4): 505-7, 2009.

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Figure 1. Clinical Pathway for the Laparoscopic Management of Peritoneal Surface Malignancies

Peritoneal Surface Malignancy Center Evaluation by a HIPEC Surgeon

CT Scan with no gross evidence of carcinomatosis

Diagnostic Laparoscopy

Peritoneal Cancer Index < 10

Peritoneal Cancer Index > 10

Laparoscopic Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Open Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

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Table 1: Characteristics of Patients with Limited Pseudomyxoma Peritonei (L-MCP) treated with Cytoreductive Surgery and HIPEC

Variable

Number of Patients (n) Mean Age Sex Male Female Previous Surgery No Yes Previous Chemotherapy No Mean Body Mass Index Mean Peritoneal Cancer Index Complete Cytoreduction Yes Bowel Resection No Yes Mean Estimated Blood Loss Mean Blood Transfused Mean Duration of Surgery Grade 3 Complications No Grade 4 Complications No Yes Mean Length of Hospital Stay Mean Follow up

Laparoscopic CRS and HIPEC

11 52 3 8 0 11 11 27 5 11 8 3 70ml 0 4.2 hours 11 10 1 6 days 12 months

Laparoscopic to Open CRS and HIPEC

1 74 0 1 0 1 1 29.1 10 1 1 0 100ml 0 5 hours 1 1 0 7 days 18 months

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