Effects of Hyperthermic Intraperitoneal Chemotherapy and Intraperitoneal Chemotherapy for Well-Differentiated Papillary Mesothelioma

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Abstract Objective: Well-Differentiated Papillary Mesothelioma (WDPM) is a rare disease, with no consensus recommendation for treatment. In the present article, we propose novel treatment options for the treatment of WDPM. Methods: From 2006 to 2023, nine patients (five male, four femail) were pathologically classified as WDPM, ranging age from 35 to 65 years. One patient showed scattered peritoneal nodules, and was treated by Laparoscopic Hyperthermic Peritoneal Perfusion (LHIPEC) alone. The remaining eight patients had multifocal peritoneal involvement, four patients were treated with LHIPEC alone. Neoadjuvant Intraoperative Chemotherapy (NIC) was administered in five cases, using Docetaxel Plus Cisplatinum (CDDP) via an intraperitoneal port system. In five cases, laparotomy and peritonectomy was accompanied by intraoperative HIPEC. Complete macroscopic resection of peritoneal nodules (CC-0) achieved in two cases, but in two other cases, CC-0 could not be performed due to diffuse involvement of the small bowel mesentery. Second and third sessions of LHIPEC were performed in six cases. Results: The peritoneal carcinomatosis index (PCI) after the first LHIPEC was 24.1 ± 8.9, and that after LHIPEC plus IP chemotherapy was16.9 ± 8.3 (N=6)(P=0.0124). Four patients treated with LHIPEC alone were alive with WDPM from 11 to 77 months or without recurrence after 92 months. The PCI for the scattered type was 3 at the 1st LHIPEC, reducing 0 at the second laparoscopy. The PCI for the multifocal type was 30 at the 1st LHIPEC, followed by completely disappearence of macroscopic nodules at the 2nd laparoscopy. In contrast, PCIs of 26 and 23 in two patients could not be reduced by LHIPEC and IP chemotherapy to the levels required for complete resection. This was due to diffuse involvement of the small bowel mesentery, One of these patients died from recurrent mesothelioma in the pleural cavity and abdominal wall with epihelioid malignant peritoneal mesothelioma on histology. She had microscopic invasive foci with atypical cells in part of resected specimen. The other case who had a peritoneal recurrence of biphasic mesothelioma is still alive. Conclusions: Most of WDPM that are either solitary or have few nodules are thought to behave benignly, however, some multifocal WDPM contain highly malignant foci. Complete cytoreduction of visible nodules after LHIPEC and IP chemotherapy combined with intraoperative HIPEC are essential for cure. Patients with multifocal WDPM who have incomplete resection may develop recurrence due to occult invasive foci and transformation into MPM. Accordingly, the resected specimen should be studied carefully to detect invasive foci. Although most WDPM have indolent biological behavior, patients should be followed carefully for many years.

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