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For peritoneal metastases from a primary appendiceal mucinous neoplasm to exist, the thin wall of the appendix must perforate to allow mucus or mucus plus tumor cells to gain access to the peritoneal spaces. The proportion of specimens containing tumor cells within mucus as compared to mucus only outside the appendix may have prognostic significance. The histopathology of tumor masses was determined from the specimens resected at the cytoreductive surgery (CRS). The presence versus absence of tumor cells in mucus and the proportion of specimens with tumor cells was determined and correlated with the overall survival of these patients. In 418 patients with a complete cytoreduction for a low-grade appendiceal mucinous neoplasm (LAMN), the cellularity of all resected specimens was determined. The hazard ratio of overall survival of patients whose specimens had no cells as compared to specimens with cells in mucus by histology was 4.41 (1.61, 12.1) (p = 0.0039). If overall survival of patients with all specimens without tumor cells was compared to patients with specimens with 1–99 % tumor and compared to patients with 100 % of specimens with tumor cells, the hazard ratios were 4.3 (1.34, 13.8) (p = 0.0143) and 9.62 (2.93, 31.6) (p = 0.0002), respectively. The cellularity of mucus within the specimens removed by a complete CRS has strong prognostic implications in LAMN patients. LAMN with acellular specimens (LAMNa) as compared to LAMN with tumor cells in specimens (LAMNb) should be staged as different histologic subtypes of mucinous appendiceal neoplasms. [ABSTRACT FROM AUTHOR]

In the past, mucinous appendiceal neoplasms (MAN) greater than 2 cm in diameter were treated by a right colon resection. New data shows that treatment options are to be determined by the histopathologic grade of the appendiceal tumor and the condition of the wall of the appendix (intact vs. breached). A 39-year-old woman had an incidental diagnosis of a low-grade appendiceal mucinous neoplasm (LAMN) at the time of a hysterectomy. The appendiceal tumor had small quantities of mucus surrounding an enlarged appendix. No tumor cells were seen in the mucus by histologic study. The patient was placed in follow-up. Eighteen years later she required treatment for advanced pseudomyxoma peritonei. When 5 different histopathologic types of MAN are considered with an intact vs. perforated wall of the appendix, four different treatment options develop. With LAMN and well or moderately differentiated mucinous appendiceal adenocarcinoma (MACA), the patient does not require operative intervention if the wall of the appendix is intact. If mucus or mucus plus tumor cells are identified outside the appendix an intervention is indicated. In patients, as the one presented, in whom only small amounts of mucus are outside the appendix, surveillance may be recommended. In patients with a diagnosed low-grade MAN, dissemination to regional lymph nodes is rare. Dissemination to the peritoneal space places the patient at risk to develop pseudomyxoma peritonei. As this case report illustrates, if surveillance is recommended, long-term follow-up is required. • A non-perforated low-grade mucinous appendiceal neoplasm requires surveillance. • A perforated low-grade mucinous appendiceal neoplasm presents a dilemma. • If epithelial cells are in the peritoneal space, reoperation with HIPEC is required. • If only a small volume of acellular mucus has escaped, follow-up may be adequate. [ABSTRACT FROM AUTHOR]

Background. A prominent part of treatment failure of gastrointestinal and gynecologic malignancy is dissemination to peritoneal surfaces. This has been associated with a limited survival and no reliable treatment strategies. Methods. A review of the natural history of carcinomatosis was performed and a rationale for intraperitoneal chemotherapy was sought. The pharmacology of chemotherapy administration into the peritoneal cavity was reviewed. Results. The technology of perioperative intraperitoneal chemotherapy requires the administration of drugs along with moderate hyperthermia in the operating room as a planned part of the surgical procedure. The solution in which the chemotherapy is diluted has an effect upon the drug clearance from the peritoneal cavity. Also, the volume of the carrier solution affects the exposure of cancer nodules on peritoneal surfaces. Conclusions. New combinations of intraperitoneal chemotherapy administration when combined with optimal surgical technology for maximal chemotherapy effects should result in benefit to patients with peritoneal surface dissemination of gastrointestinal and gynecologic malignancy. [ABSTRACT FROM AUTHOR]

Background. Peritoneal surface malignancy can result from full thickness invasion of gastrointestinal cancer through the bowel wall or from dissemination of cancer cells from the trauma of cancer surgery. In the past, this clinical situation was treated only with palliative intent. Methods. An aggressive approach to peritoneal surface malignancy involves peritonectomy procedures, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The clinical assessments necessary for valid clinical judgements include the cancer histopathology (invasive vs. expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. Results. In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 50% with selected patients. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. Conclusions. Oncologists must accept responsibility for knowledgeable management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in both phase II studies and phase III studies. All historical controls show 0% long-term survival. Surgical interventions combined with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs must be considered a treatment option. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer has in the past been regarded as a lethal extension of the malignant process. Natural history studies have confirmed that this is so in the absence of special treatments. Recently, a combined treatment approach which utilizes cytoreductive surgery to remove all visible disease within the abdomen and pelvis followed by perioperative intraperitoneal chemotherapy has demonstrated success in phase II and phase III studies. The greatest benefit has been seen with appendiceal malignancy with cure rates approaching 80%. Also, colon cancer has been cured in approximately 30% of patients with complete removal of tumor by cytoreductive surgery. The morbidity and mortality of these procedures compares well with other gastrointestinal cancer operations. One may conclude that selected patients with carcinomatosis should expect long-term survival with a combined treatment approach using cytoreductive surgery with perioperative intraperitoneal chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to report the pharmacokinetics of heated intraoperative intraperitoneal mitomycin C (MMC) and to analyze the impact of heat, extent of peritoneal resections, and effect of intraoperative hyperthermic chemotherapy on the pharmacological properties of the peritoneal plasma barrier. Methods: Sixty patients with peritoneal carcinomatosis were included in a phase I/II study combining cytoreductive surgery with 2 h of heated intraperitoneal mitomycin C in an intraoperative lavage technique and one cycle of early postoperative 5-fluorouracil (5-FU) given on postoperative days 1–5. Three pharmacokinetic analyses were performed: (1) pharmacokinetics of heated intraoperative intraperitoneal MMC was determined for 18 patients by sampling peritoneal fluid, plasma, and urine during the 2-h procedure; (2) impact of peritoneal resections on MMC pharmacokinetics was assessed by comparing a group of patients who underwent ≤1 peritonectomy procedure (minimal surgery) to a group of patients who underwent ≥2 peritonectomy procedures (extensive surgery), and (3) effects of heated intraoperative intraperitoneal chemotherapy on the pharmacokinetics of early postoperative intraperitoneal 5-FU by comparing a group of patients treated with heated intraoperative intraperitoneal MMC to a control group who did not receive heated intraoperative intraperitoneal chemotherapy. Results: The mean dose of heated intraoperative intraperitoneal MMC per patient was 22.5 ± 7.1 mg (12.9 ± 3.8 mg/m[sup 2] ). Drug absorption from perfusate was 14.3 ± 2.7 mg. The mean aeras under the curve (AUC) for perfusate and plasma were, respectively, 340 ± 138 and 15 ± 4 µg/ml × min. The mean AUC peritoneal fluid/plasma ratio was 23.5 ± 5.8. Patients who underwent extensive peritoneal resections exhibited a significantly (p = 0.037; Wilcoxon rank test) increased peak plasma concentration of MMC, a significantly (p = 0.029) increased AUC of plasma concentrations and a significantly (p = 0.034) decreased peritoneal fluid/plasma AUC ratio. Pharmacokinetic studies of early postoperative intraperitoneal 5-FU showed no significant difference in plasma AUC, perfusate AUC and AUC ratio between patients who received and those who did not receive heated intraoperative intraperitoneal MMC. Conclusions: Heated intraoperative intraperitoneal chemotherapy achieves high peritoneal concentrations of MMC with limited systemic absorption. Systemic drug absorption during heated intraoperative intraperitoneal chemotherapy is increased when extensive peritoneal resections are performed, but such slight increases are unlikely to change the risk of systemic drug toxicities. Heated intraoperative intraperitoneal chemotherapy does not alter the pharmacokinetics of early postoperative intraperitoneal 5-FU. [ABSTRACT FROM AUTHOR]