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Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for selected patients with pseudomyxoma peritonei (PMP) and diffuse malignant peritoneal mesothelioma (DMPM). Tumor infiltration of the hemidiaphragm requiring partial resection occurs as a result of large volume and/or invasive disease at this anatomic site. Transmission of disease from abdomen to chest is a great danger in this group of patients. From a prospective database, patients who had diaphragm resection and then hyperthermic thoracoabdominal chemotherapy (HITAC) as a component of a cytoreductive surgical procedure were identified. Data from control patients receiving HIPEC or hyperthermic intrathoracic chemotherapy (HITOC) were analyzed for comparison. The morbidity, mortality, survival, and recurrence rate within the thoracic space were presented. Thirty patients had partial resection of a hemidiaphragm as part of a cytoreductive surgical procedure that utilized HITAC. The pharmacologic benefit of intracavitary chemotherapy administration was documented with an area under the curve ratio of intracavitary concentration times time to plasma concentration times time of 27 ± 10 for mitomycin C and 75 ± 26 for doxorubicin. Comparing percent chemotherapy absorbed for a ninety-minute treatment showed the largest for HIPEC, then for HITAC, and lowest for HITOC. The incidence of grade 3 and 4 adverse events was 43%. There was no mortality. Adjustments in the chemotherapy dose are not necessary with HITAC. The morbidity was high, the survival was acceptable, and intrathoracic recurrence was low. [ABSTRACT FROM AUTHOR]

In patients with pseudomyxoma peritonei or peritoneal mesothelioma, direct extension of disease through the hemidiaphragm may result in an isolated progression of tumor within the pleural space. We monitored the intrapleural and plasma levels of mitomycin C and doxorubicin by HPLC assay in order to determine the pharmacokinetic behavior of this intracavitary use of chemotherapy. Our results showed a persistent high concentration of intrapleural drug as compared to plasma concentrations. The increased exposure for mitomycin C was 96, and the increased exposure for doxorubicin was 241. When the clearance of chemotherapy from the thoracic cavity was compared to clearance from the abdomen and pelvis, there was a considerably more rapid clearance from the abdomen as compared to the thorax. The pharmacologic study of intrapleural chemotherapy in these patients provides a strong pharmacologic rationale for regional chemotherapy in this group of patients. [ABSTRACT FROM AUTHOR]