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Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal metastases. The optimal agents for HIPEC have not been established.Melphalan is a drug with broad activity and a favorable profile for intraperitoneal application. The purpose of this study is to review our experience using melphalan for HIPEC. Pharmacologic data was obtained. Thirty four patients who underwent CRS for peritoneal metastases received melphalan for HIPEC between 2003 and 2011. The first 10 patients received 70mg/m2; subsequent 24 received 60 or 70mg/m2. The mean PCI was 21}7. Twenty-eight patients (83%) had a CC score of 1 or 2. The mean length of stay was 18 } 2 days. Nine patients (26%) had a grade 3 and 6 (17%) had grade 4 morbidity. There were no postoperative deaths. The pharmacologic analysis of plasma to peritoneal fluid levels of melphalan showed an AUC ratio of 33 while the tumor nodules to peritoneal ratio was 8. Melphalan is an acceptable agent for use in HIPEC. The morbidity of intraperitoneal melphalan at the dose of 60-70 mg/m2 appears acceptable. Further studies comparing the effectiveness of melphalan and other HIPEC agents are needed. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC) was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement. [ABSTRACT FROM AUTHOR]

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]

Peritoneal metastases (PM) are a common presentation for patients with metastatic colorectal cancer (CRC), and the median survival of patients with PM is approximately one year. In a majority of patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery (CRS) and heated perioperative chemotherapy (HIPEC) as a standard approach for selected patients with PM from CRC. These investigators have demonstrated a very promising long-term survival in a subset of patients with a limited amount of isolated peritoneal metastatic disease. This paper presents the data that supports CRS and HIPEC as a treatment option for CRC patients with PM. These results of treatment are compared and contrasted to the results that can be expected with systemic chemotherapy alone. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) with hyperthermic perioperative chemotherapy (HIPEC) has become a treatment option for selected patients with peritoneal metastases (PMs) from gastrointestinal malignancies. The purpose of this study is to evaluate our most recent data regarding pulmonary complications (respiratory distress, pleural effusion, and pneumonia) and attempt to identify risk factors associated with this management plan. This study includes the most recent 4-year experience with appendiceal and colorectal carcinomatosis patients treated in a uniform manner between January 1, 2006 and December 31, 2009. A prospective morbidity and mortality database was maintained and pulmonary adverse events were analyzed with special attention to subphrenic peritonectomy. There were 147 consecutive patients with a mean age of 49.9 years. Fourteen patients (10%) presented grades I-IV pulmonary complications for a total of 26 events. The peritonectomy of right upper quadrant was performed in 74% and right plus left in 49% of the patients. Statistically, there were no more pulmonary complications among patients submitted to peritoneal stripping of right or right and left hemidiaphragm as compared to no subdiaphragmatic peritonectomy (P = 1.00 and P = 0.58, resp.). In an analysis of 18 quantitative indicators and clinical variables with pulmonary adverse events, only blood replacement greater than six units showed a significant correlation (P = 0.0062). Pulmonary adverse events were observed in 10% of patients having CRS and HIPEC. Subphrenic peritonectomy was not a specific risk factor for developing these adverse events. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss various articles on pharmacokinetics during intrapertieoneal chemotherapy published in this issue of the periodical.

Background and Objectives. Systemic chemotherapy administered prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mucinous adenocarcinoma of appendiceal origin (PMCA) is associated with a significant rate of histological response. The impact of preoperative systemic chemotherapy (PSC) on intraperitoneal tumor burden, completeness of cytoreduction, and perioperative complications is unknown. Methods. We analyzed prospectively collected data from our HIPEC database. Thirty-four patients with PMCA were prospectively recruited and treated with PSC. Perioperative variables and survival in this group of patients were compared against 24 patients with PMCA who did not receive PSC. Results. Ten of 34 patients (29%) receiving PSC had a complete or near complete histological response. Patients receiving PSC had a lower peritoneal carcinomatosis index, required fewer peritonectomies and visceral resections, and achieved complete cytoreduction more frequently compared to patients with no preoperative chemotherapy. The incidence of perioperative complications and survival were not significantly different between the two groups. However, patients with complete histological response had better overall survival compared to patients without complete response. Conclusions. Preoperative systemic chemotherapy in appendix-originated PMCA is associated with a significant rate of histological response which may reduce the tumor burden, facilitate less aggressive and more complete CRS, and improve short-term survival in patients with a significant histological response. [ABSTRACT FROM AUTHOR]