Research Article

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

by Yutaka Yonemura1-3*, Haruaki Ishibashi2, Ching-Hsien Ling2, Takuji Fujita2, Yang Liu2, Sachio Fushida2, Toshiyuki Kitai2, Yasuo Hirono2, Shouzou Sako2, Akiyoshi Mizumoto3, Nobuyuki Takao3, Keizou Taniguchi4, Daisuke Fujimoto4

1Asian School of Peritoneal Surface Malignancy Treatment, Kyoto City, Kyoto Prefecture, 600-8189, Japan

2Department of Regional Cancer Therapy, Peritoneal Dissemination Center, Kishiwada Tokushukai Hospital, Kishiwada City, Oosaka Prefecture, 596-8522, Japan

3Department of Regional Cancer Therapy, Peritoneal Dissemination Center, Kusatsu General Hospital, Kusatsu City, Shiga Prefecture, 525-8585n, Japan

4Department of Surgery, Mizonokuchi Hospital, Teikyo University, School of medicine, Kawasaki, Kanagawa, 213-8507, Japan

5Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8654, Japan

*Corresponding author: Yutaka Yonemura, Representative of Asian School of Peritoneal Surface Malignancy Treatment, Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital, Osaka, Japan

Received Date: 18 May 2024

Accepted Date: 23 May 2024

Published Date: 25 May 2024

Citation: Yonemura Y, Ishibashi H, Ling CH, Fujita T, Liu Y, et al. (2024) Effects of Hyperthermic Intraperitoneal Chemotherapy and Intraperitoneal Chemotherapy for Well-Differentiated Papillary Mesothelioma. J Surg 9: 11059


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.

Keywords: HIPEC; Mesothelioma; Peritoneal cancer index; Peritoneal metastasis; Peritonectomy; WDPM; Well differentiated papillary mesothelioma


Well-Differentiated Papillary Mesothelioma (WDPM) is one of the groups of peritoneal mesothelioma [1]. Deraco M et al. classified the disease as a borderline malignancy in malignant peritoneal mesothelioma (MPM), and occupies 10.4% (105/1103) of all MPM [2]. Most articles about WDPM reported that the biological characters of the disease show a benign course, but some cases progress to malignant transformation [3]. Accordingly, this disease has a broad spectrum of malignancy [4]. However, the incidence of WDPM is very rare, and no consensus for the recommendation of treatment option has been described. In the present article, we report the data of our experiences of 9 patients with WDPM, and propose some treatment options for the treatment of WDPM

Patients and Methods

From 2006 to 2023, 107 patients with MPM were referred to our hospitals, and 9 (8.4%), 84 (78.5%), 9 (8.4%) and 5 (4.7%) were pathologically classified into WDPM, epithelioid, biphasic, and sarcomatoid type, respectively, according to the classification of WHO from biopsied materials and resected specimens. Among 9 WDPM patients, 5 were male and 4 were female, and the age range from 35 to 65 with mean age of 45.1 years old (Table 1). Case one showed scattered nodules (5 small nodules of smaller than 5 mm in diameter on the small bowel mesentery and one nodule of 6 mm in diameter on the caecum) (Figure 1). Biopsied material showed typical papillary architecture containing fibrovasular cores with a single lining of cuboidal mesothelial cells without atypia or mitoses on the peritoneal surface. She was treated by Laparoscopic Hyperthermic Peritoneal Chemotherapy (LHIPEC) with 20mg of mitomycin C (MMC) and 100mg of cisplatinum (CDDP) (Tables 1,2). She is alive without recurrence 7 years after LHIPEC.


Figure 1: Scattered type of WDPM (case 1), 2-3 mm of several nodules were found on the small bowel mesentery.

The other 8 patients showed multifocal involvement of peritoneal surface with small nodules of 2-3 mm in diameter (Figure 2). Eight patients except case 6 were received laparoscopy and LHIPEC. Four patients (Case 1, 2, 5, and 7) were treated with LHIPEC alone, using MMC + CDDP for case 1 and 2 or MMC + Gemicitabine (1000mg/body) for case, 5 and 7. Neoadjuvant intraoperative chemotherapy (NIC) using 40mg of docetaxel plus 40mg of CDDP through intraperitoneal port system was performed in case 2, 3, 4, 7, and 8 (Table 3). In case 3, 4, 6, 8, and 9, laparotomy was performed and peritonectomy was done accompanying with intraoperative HIPEC. Complete macroscopic resection of peritoneal nodules (CCR-0) could be done in case 3, and 4, but in case 8, and 9, CCR-0 could not be performed due to diffuse involvement of small bowel mesentery. Specimens of all these 9 patients histologically shows a mesothelial proliferation with a papillary architecture, a myxoid appearance to the papillary cores , and a sigle layer of cytologically bland mesothelial cells covering the papillae, with small number of KI-67 labelled cells (Figure 5) and absence of invasion to other organs [5].