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Operating Room Environmental Safety With Heated Intraperitoneal Chemotherapy

Washington Cancer Institute, Washington, DC
Center to Protect Workers Rights, Silver Spring, Maryland
Program in Peritoneal Surface Malignancy, Washington Cancer Institute, Washington, DC

To the Editor:

It is clear that this new timing for intraperitoneal chemotherapy has demonstrated great potential for eradication of peritoneal surface dissemination of cancer. In midyear 2003, cytoreductive surgery with intraperitoneal chemotherapy represents standard of care for appendiceal malignancy with peritoneal dissemination, for malignant peritoneal mesothelioma, and for selected patients with carcinomatosis from colon cancer.^1–3

As with any new surgical technology institutional variations exist in the delivery of drugs, the scheduling, and in this situation, the magnitude of the hyperthermia. A number of institutions deliver the drug into a closed peritoneal space after all surgery including intestinal reconstruction has been completed. Other institutions use a technique that relies on the surgeon’s double-gloved hand to uniformly distribute the heat and the chemotherapy to all surfaces of the abdomen and pelvis before the performance of any intestinal anastomoses. Although no comparative studies have been done, it is possible that this technology is safer for patients providing a lower morbidity and mortality and a greater efficacy because of the uniform heat and drug delivery.⁴ Clearly, now that the efficacy of these treatments have been demonstrated and the morbidity and mortality for patients has been established, the logistical considerations for hyperthermic intraoperative chemotherapy need to be considered.⁵ Of paramount importance is the safety of this treatment for personnel in the operating room.

Dr. Connor and colleagues question our air sampling technique, which escapes into the air possibly contaminated mitomycin C through methanol. Dr. Connor questions if part of the mitomycin C is lost as a result of the evaporation of methanol. We have tested our recovery technique. If as little as 5 µg of mitomycin C is placed in 500 mL of methanol and the methanol evaporated, approximately 85% of the mitomycin C will be recovered postevaporation by high-pressure liquid chromatography testing. This technology of methanol extraction of mitomycin C is repeatedly used in our laboratory and in other laboratories around the world without significant loss of mitomycin C. We thought then and still think now that this method for detecting aerosolized mitomycin C is appropriate.

We did research the article by Connor et al. regarding the vaporization of mutagenic neoplastic agents at 23°C and 37°C.⁶ We were pleased to find that their data corroborated ours in that there was no mitomycin C vaporization detected at either temperature.

It may be of some interest to Dr. Connor and his colleagues that our article was submitted to the Annals of Surgical Oncology in August 2000. At that time we did not have the benefit of his fine publication in Mutation Research, which appeared in October of that same year. Obviously, the article by Kiffmeyer et al.⁷ published in 2002 using the cryotrap was not available to us at the time of submission of our safety monitoring article.⁸ All the new technologies relevant to our publication were published after the submission of our article.

When this study was performed the smoke evacuation device that we used was manufactured by Stackhouse, El Secunda, California. Their manufacturer specifications for the charcoal filtration unit clearly indicated complete extraction of mitomycin C and water vapor from the column of air. Unfortunately, the charcoal filter used in 2000 is currently not available. Neither the effectiveness of this charcoal filter nor the possibility to desorb mitomycin C from it can be tested.⁹ In a recent experiment on a different smoke filtration device the recovery of mitomycin C was large but most of the drug was in a fiberglass mesh that supports the activated charcoal.

Connor and colleagues are correct in their explanation of the human metabolism of mitomycin C. They have no data and we have no data regarding the metabolism and excretion of mitomycin C taken in through the lungs or by direct absorption through the skin. However, our study would not have been complete without an attempt to find drug in the urine of persons closest to the open peritoneal cavity of the patient. We thought that this was the surgeon who was manipulating the viscera and the perfusionist who was operating the equipment. No matter what the metabolism of the mitomycin C, we found no drug in the urine of the surgeon or the perfusionist. Of course, this does not mean that no mitomycin C exposure occurred. What it does mean is that any possible exposure was below the limits of detection of our high-pressure liquid chromatography system.

We are encouraged that Dr. Connor and his colleagues have continued the work in this important field. Monitoring the occupational exposure to antineoplastic agents in a health care setting is crucial. This takes on an added importance as chemotherapy moves from an oncology infusion center and oncology nursing unit into the operating room. We are hopeful that Dr. Connor and his colleagues will continue in their attempts to document the innovative new methodologies for chemotherapy detection. We look forward to reading publications by Dr. Connor and his colleagues regarding environmental safety in the operating room using heated intraoperative intraperitoneal chemotherapy. We agree that continued studies to determine worker exposure to potentially hazardous procedures is indicated. We also agree that an absence of risk in this new treatment modality cannot be assumed and that with each new drug that is introduced, similar studies of the environment, of the personnel, and of glove permeability should occur.

To our knowledge this article, published in the Annals of Surgical Oncology, is the only one that attempted to critically evaluate the environmental impact of intraoperative chemotherapy.⁸ There are scores of units operative throughout the world. I would hope that similar studies might be carried out at other institutions.

REFERENCES

1. Sugarbaker PH. Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol 1999; 6: 727–31.[Abstract]
2. Carroll NM, Mohamed F, Sugarbaker PH, Alexander R. Surgery, hyperthermic perfusion and postoperative chemotherapy: The NIH and Washington Hospital Center experience. In: Pass HI, Vogelzang N, Carbone M, eds. Malignant Mesothelioma: Advances in Pathogenesis, Diagnosis and Translational Therapies. New York: Springer-Verlag Publishing, 2002 (in press).
3. Glehen O, Sugarbaker PH. New perspectives in the management of colorectal cancer; what about peritoneal carcinomatosis? Scand J Surg 2003; 92: 178–9.[Medline]
4. Elias D, Antoun S, Goharin A, et al. Research on the best chemohyperthermia technique of treatment of peritoneal carcinomatosis after complete resection. Int J Surg Investig 2000; 1: 431–9.[Medline]
5. Glehen O, Osinsky D, Cotte E, et al. Intraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol (in press).
6. Connor TH, Shults M, Fraser MP. Determination of the vaporization of mutagenic antineoplastic agents at 23 and 37°C using a dessicator technique. Mutat Res 2000; 470: 85–92.[Medline]
7. Kiffemeyer TK, Kube C, Opiolka S, Schmidt KG, Schöppe G, Sessnick PHM. Vapour pressures, evaporation behavior and airborne concentrations of hazardous drugs: implications for occupational safety. Pharmaceut J 2002; 268: 331–7.
8. Stuart OA, Stephens AD, Welch L, Sugarbaker PH. Safety monitoring of the coliseum technique for heated intraoperative intraperitoneal chemotherapy with mitomycin C. Ann Surg Oncol 2002; 9: 186–91.[Abstract/Free Full Text]
9. Larson RR, Dillon HK, Khazaeli MB. A new monitoring method using solid sorbent media for evaluation of airborne cyclophosphamide and other neoplastic agents. Appl Occup Environ Hyg 2003; 18: 120–31.[CrossRef][Medline]

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