Malignant Peritoneal Mesothelioma Research Articles

Malignant peritoneal mesothelioma

Malignant mesothelioma is one of the rare disease. It is an aggressive tumor arising from the mesothelial lining of the pleura or peritoneum. In our country there is no reported data or known incidence rate. It has an association with exposure to asbestos and usually has a poor prognosis. Early diagnosis and establishment of a standard treatment for malignant peritoneal mesothelioma is difficult. We report on a case of malignant peritoneal mesothelioma in a 59-year-old man with huge abdominal swelling, ascites and respiratory distress.KYAMC Journal Vol. 8, No.-2, Jan 2018, Page 40-42

Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study

BackgroundThe differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients. MethodsMarkers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC). ResultsMean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81–23.05; P = 0.004). ConclusionWhen assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.

Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) benefits selected patients with peritoneal mesothelioma. We present the outcomes of this treatment strategy in a UK peritoneal malignancy national referral centre.Methods: Observational retrospective analysis of data prospectively collected in a dedicated peritoneal malignancy database between March 1998 and January 2016.Results: Of 1586 patients treated for peritoneal malignancy, 76 (4.8%) underwent surgery for peritoneal mesothelioma. Median age was 49 years (range 21–73 years). 34 patients (45%) were female. Of the 76 patients, 39 (51%) had low grade histological subtypes (mostly multicystic mesothelioma), and 37 (49%) had diffuse malignant peritoneal mesothelioma (DMPM; mostly epithelioid mesothelioma). Complete cytoreduction was achieved in 52 patients (68%) and maximal tumour debulking (MTD) was performed in 20 patients (26%); the remaining 4 patients (5%) underwent a laparotomy with biopsy only. HIPEC was administered in 67 patients (88%). Median overall (OS) and disease-free survival (DFS) after CRS was 97.8 (80.2–115.4) and 58.8 (47.4–70.3) months, respectively. After complete cytoreduction, 100% overall survival was observed amongst patients with low-grade disease. Ki-67 proliferation index was significantly associated with survival outcomes after complete cytoreduction for DMPM and was an independent predictor of decreased survival.Conclusion: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma.

Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity. The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM. The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly.Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is<1year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1year. The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

Malignant peritoneal mesothelioma: Clinicopathological features, prognostic factors, and survival outcomes.

650 Background: Peritoneal mesothelioma (PeM) is an orphan disease with approximately 300-400 cases diagnosed in the United States each year. Due to its rarity, data on its presentation and prognostic factors is limited. The purpose of this study was to investigate the clinicopathological profile and outcome of Malignant PeM (MPeM). Methods: We retrospectively reviewed 128 PeM patients (pts) seen at UTMDACC (2011 - 2017) comprised of 111 MPeM and 17 variants (VPeM) [9 well-differentiated papillary and 8 multicystic]. Kaplan-Meier method was used to estimate median overall survival (mOS) and compared with log-rank tests. Results: Median age at diagnosis was 57 yrs. with a higher proportion of women (61%). The mOS for MPeM was significantly shorter than VPeM (HR 3.7, 95% CI: 1.6 – 8.4, P = 0.002). Among pts with MPeM, median age at diagnosis was 56 yrs. and 58% were women. Only 22% had prior exposure to asbestos. Epithelioid subtype was seen in 94 (85%) pts. Calretinin and WT-1 IHC were positive in 98% and 96% of cases. BerEP4 and MOC-31 IHC were negative in 90% and 84% of cases. After median follow-up of 31 months (m), the mOS for MPeM cohort was 78 m. In univariate analysis, age, prior asbestos exposure, ECOG PS, histologic subtype, CA125, neutrophil-lymphocyte ratio (NLR) and cytoreductive surgery (CRS) were found to be associated with OS. In multivariate analyses, age ≥ 65 years (HR 4.5, 95% CI: 1.3 - 15.2, P = 0.02), prior asbestos exposure (HR 4.1, 95% CI: 1.1 – 15.6, P = 0.04), poor PS (ECOG 2/3) (HR 8.9, 95% CI: 1.7 – 47.7, P = 0.01), elevated CA125 ( &gt; 3X upper limit of normal) (HR 4.5, 95% CI: 1.3 – 15.5, P = 0.02), and high NLR (HR 3.8, 95% CI: 1.1 – 12.6, P = 0.03) were found to be independently associated with poor OS. A total of 50 (45%) pts underwent CRS and among these the completion of cytoreduction score (CCS) was strongly associated with OS (mOS: 201 m, 53 m and 36 m for CCS 0, 1, 2/3, respectively, P = 0.005). Conclusions: MPeM is associated with poor survival outcomes. Prognostic factors include age, history of asbestos exposure, CA-125 level, NLR, and PS. CRS with CCS 0 results in favorable survival. Further understanding of molecular genetics is warranted to improve prognostication and outcomes.

Malignant peritoneal mesothelioma: clinical aspects, and therapeutic perspectives.

Malignant peritoneal mesothelioma (MPM) is a rare disease with a wide clinical spectrum. It arises from the peritoneal lining and commonly presents with diffuse, extensive spread throughout the abdomen and, more rarely, metastatic spread beyond the abdominal cavity. Computed tomography, magnetic resonance imaging and positron-emission tomography are important diagnostic tools used for the preoperative staging of MPM. The definitive diagnosis is based on histopathological analysis, mainly via immunohistochemistry. In this regard, paired-box gene 8 negativity represents a useful diagnostic biomarker for differentiating MPM from ovarian carcinoma. In addition, BRCA1-associated protein-1 (BAP1) loss is specific to MPM and allows it to be distinguished from both benign mesothelial lesions and ovarian serous tumors. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an increasingly important therapeutic approach, while systemic therapies are still being developed. Histology, Ki-67, completeness of cytoreduction, age, sex, and baseline thrombocytosis are commonly used to optimize patient selection for CRS with HIPEC. Additionally, it is well recognized that, compared to other subtypes, an epithelial morphology is associated with a favorable prognosis, whereas baseline thrombocytosis predicts an aggressive biologicalbehavior. Platelets and other immunologic cytokines have been evaluated as potential novel therapeutic targets. Epigenetic modifiers, including BAP1, SETD2 and DDX3X, are crucial in mesothelial tumorigenesis and provide opportunities for targeted treatment. Overexpression of the closely interacting phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways appears crucial in regulation of the malignant phenotype. The use of targeted therapies with PI3K-mTOR-based inhibitors requires further clinical assessment as a novel approach.

Malignant Peritoneal Mesothelioma: A Rare Cause of Ascites.

Malignant peritoneal mesothelioma (MPM) is a rare diagnosis that presents with difficulties in diagnosis and management. This article reports a case of an 88-year-old male who presented with a 2-week history of abdominal distention and bloating. He worked at an insulation production factory between the ages of 23 and 25 years with presumed asbestos exposure. On the computed tomography scan of the abdomen/pelvis, the patient was found to have diffuse omental, peritoneal, and mesenteric nodularity with moderate to large ascites. Omental biopsy revealed MPM. The overall prognosis of MPM remains poor, with a median survival time of 12 months at the time of diagnosis. Treatment modalities offered in the United States include chemotherapy alone, cytoreductive surgery alone, or cytoreductive surgery/chemotherapy combination.

Prognostic Significance of Blood, Serum, and Ascites Parameters in Patients with Malignant Peritoneal Mesothelioma or Peritoneal Carcinomatosis.

To determine effects of the biochemical and cytological properties of blood, serum, and ascites on survival of patients with malignant peritoneal effusion (MPeE), including malignant peritoneal mesothelioma (MPeM) and peritoneal carcinomatosis (PC), we conducted a retrospective study of patients with MPeE and healthy controls. Potential prognostic factors were identified as follows: age, sex, blood neutrophil-to-lymphocyte ratio (NLR), serum parameters, ascites parameters, serum-ascites albumin gradient, and the ascites-serum LDH ratio. Compared to those of the control group, serum albumin levels were significantly lower, and the NLR and serum LDH levels were significantly higher in the MPeE group. Overall survival (OS) was longer in patients with MPeM compared to that in patients with PC. Compared with patients in the MPeM, patients with PC had higher NLRs, ascites glucose levels, serum-ascites albumin gradients, and serum LDH levels. In contrast, their ascites albumin levels and ascites-serum LDH ratios were lower. Univariate analyses indicated that the NLR, serum LDH levels, ascites LDH levels, ascites coenocyte levels, and the ascites coenocyte-to-monocyte ratios affected the OS. Multivariate analyses identified only serum and ascites LDH levels as independent prognostic factors.

AB016. Pleurectomy/decortication for malignant pleural mesothelioma

AB016. Pleurectomy/decortication for malignant pleural mesothelioma

Mesothelioma from Asbestos Exposure in Brake Mechanics: Epidemiology in Context

Asbestos causes pleural and peritoneal malignant mesothelioma, in addition to lung cancer, other cancers and asbestosis and pleural plaques. Multiple scientific disciplines have made significant contributions to the strength of the cancer causality consensus conclusion which has led many countries to ban the use of asbestos. Epidemiology has been applied to the study of automobile repair workers who have been exposed to asbestos from the replacement and installation of brakes containing asbestos. It is important to clear up the misunderstandings of the limits of epidemiology methods and their interpretation in the investigation of brake repair workers in order to prevent mesothelioma and other asbestos diseases in developing countries which are continuing to use asbestos in brake pads and for other uses.

A case of peritoneal malignant mesothelioma following radiation therapy for cervical cancer.

The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively. The patient underwent concurrent chemoradiotherapy (CCRT), and a complete response was achieved. After 54 months, ascites was found at the rectouterine pouch, but peritoneal cytology suggested reactive mesothelial cell. After 62 months of CCRT, magnetic resonance imaging revealed masses in both the salpinges. The serum levels of SCC and CA125 were 0.9 ng/ml and 506.1 U/ml, respectively. Following this, left salpingectomy and peritoneal biopsy were performed laparoscopically. Histologic examination revealed atypical mesothelial cells with no continuity of background tubal epithelium. Immunohistochemistry showed positive staining for calretinin, thrombomodulin, mesothelin and glucose transporter 1. Based on these findings, the patient was diagnosed with PMM epithelioid type and underwent systemic chemotherapy; stable disease status has been obtained for 3 months. This case demonstrates the possibility of PMM occurrence within 10 years after radiotherapy, and indicates the importance of histological and immunohistochemical examination, particularly in cases of an atypical tumorigenesis pattern from the primary cancer.

Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation.

Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs). These mutations all clustered into one of five recurrent hotspots within the WD40 repeat domains at the C-terminus of the protein. Functional studies in vitro revealed that expression of mutant but not wildtype TRAF7 led to increased phosphorylation of nuclear factor-kappa B (NF-kB) and increased expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation. Immunohistochemistry demonstrated robust L1CAM expression in adenomatoid tumors that was absent in normal mesothelial cells, malignant peritoneal mesotheliomas, and multilocular peritoneal inclusion cysts. Together, these studies demonstrate that adenomatoid tumors of the male and female genital tract are genetically defined by TRAF7 mutation that drives aberrant NF-kB pathway activation.

Recurrence of Optimally Treated Malignant Peritoneal Mesothelioma with Cytoreduction and Heated Intraperitoneal Chemotherapy.

The prognosis for patients with diffuse malignant peritoneal mesothelioma has dramatically improved with cytoreductive surgery and intraperitoneal chemotherapy. Little is known about disease recurrence after treatment. We analyzed the time to and predictors of recurrence in a large cohort of optimally treated patients. We examined 113 patients completing a two-stage cytoreduction and intraperitoneal chemotherapy protocol. All patients achieved optimal surgical resection with completeness of cytoreduction (CC) score≤1 and were divided into two groups based on absence (Group A) or presence (Group B) of gross disease at the outset of the second operation. Predictors of disease recurrence and recurrence-free survival (RFS) were determined using Cox proportional hazard regression modeling, and estimates were obtained by using the Kaplan-Meier method. Forty-six percent of patients had no gross evidence of disease at the second operation; the remaining 54% were cytoreduced to CC≤1 (Group B). Forty-two percent of patients developed disease recurrence with a median recurrence-free survival of 38.5months for the cohort; 79% of these received a form of iterative treatment. There was no statistically significant difference in recurrence-free survival between Group A (median RFS: 44.6months) and B (median RFS: 35.5months) (log-rank test, p=0.06). Additionally, the only variable significantly associated with RFS was male gender (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.16-3.38). Absence of gross disease at the second operation was not statistically protective against recurrence compared with presence of quantifiable residual disease (Group B) that was effectively cytoreduced. Long-term disease surveillance is recommended, because recurrence continues years after treatment. Where a question of recurrence arises on surveillance, males may benefit from a higher degree of suspicion.

Perplexing Malignant Peritoneal Mesothelioma in a Young Woman Without Exposure

Introduction: Malignant mesothelioma is a rare disease that most often occurs in the pleura as a result of environmental exposure. Malignant peritoneal mesothelioma (MPM) is an even less common disease, accounting for approximately 10-15% of all cases of mesothelioma. Interestingly, MPM occurs more often in females than pleural mesotheliomas do for reasons that are not entirely understood. This higher proportion of females is thought to reflect their higher incidence of non-asbestos related disease. We report the case of a young woman with no known environmental exposure history who was diagnosed with MPM. Case Report: A healthy 20-year-old woman presented with dehydration and malnutrition. She reported a 2 month history of nausea, vomiting, diarrhea and abdominal pain. She also endorsed anorexia and an associated 20-30 pound weight loss over the same period. She had presented to her local emergency department 3 times with these complaints and had been found to have small pockets of ascites as well as hepatic sinusoidal dilatation on ultrasound. Additional workup including CT imaging, liver biopsy, paracentesis, colonoscopy and upper endoscopy had failed to identify any pathology. An MRI showed extensive soft tissue implants and omental caking in the abdomen and pelvis with abnormal peritoneal thickening and enhancement. The patient underwent a CT-guided biopsy of the omental soft tissue, which demonstrated a mesothelioma of epithelioid type. She was treated with peritonectomy, omentectomy, small bowel resection, total abdominal hysterectomy and installation and circulation of hyperthermic intraperitoneal chemotherapy. Biopsies of all sampled tissue showed extensive involvement by MPM. Of note, extensive imaging and evaluation did not capture any pleural involvement. Discussion: MPM is an exceedingly rare disease. Although previous studies have demonstrated an association between MPM and asbestos exposure in men, the same association has not been deduced in female populations. Other contributing exposures that have been described include radiation, chronic peritonitis, mica exposure and the simian virus-40. Both this patient's young age and lack of any such exposures reinforce the prevailing current wisdom that the risk factors for this rare, yet highly deadly disease have yet to be properly defined.Figure: A) Coronal MRI revealing broad sheet of omental caking along the left abdomen extending into the pelvis and diffuse peritoneal thickening and enhancement both along the abdominal wall and the bowel surfaces. Overall findings are suspicious for peritoneal malignancy. B) Coronal MRI revealing overall reduction in diffuse peritoneal disease burden with resolution of omental caking after therapy.

Peritoneal Mesothelioma: A Challenge to Medical Profession

Malignant peritoneal mesothelioma (MPM) is an extremely rare cancer of peritoneum. It is associated with very poor prognosis due to late presentation and non-specific symptoms. We present a case of primary peritoneal mesothelioma in a 54 year old Hispanic female. She presented with epigastric abdominal pain and bloating for 5 months in the background of chronic non-specific abdominal discomfort. She had no history of occupational asbestos exposure, family history of cancer, smoking or weight loss. Her hemoglobin and chemistry were normal. Initial abdominal CT showed non-specific changes including loculated intra-abdominal ascites and mild epiphrenic adenopathy. Patient was referred for diagnostic laparoscopy. However, surgeons did not proceed with a surgical intervention initially. Her upper endoscopy and cystoscopy were performed and were normal. Her prior colonoscopy was normal. Repeat abdominal CT scan 3 month later revealed moderate volume of abdominal and pelvic ascites, worsening epiphrenic adenopathy, and mildly thickened anterior urinary bladder wall. Diagnostic laparoscopy was performed. Numerous implants were found on serosal surface of internal organs, peritoneum and omentum. Pathology specimen was consistent with malignant mesothelioma-Epithelioid type. Patient underwent debulking surgery, including resection and reconstructions of right hemi-diaphragm, cholecystectomy, right colectomy, partial gastrectomy, distal pancreatectomy, splenectomy, transverse colectomy, with temporary loop ileostomy followed by hyperthermic intraperitoneal chemotherapy (HIPEC) and cisplatin therapy for 6 months. Patient is disease free at 3 years postoperatively, and she is doing well with close follow-up. Malignant peritoneal mesothelioma is very difficult to diagnose due to nonspecific clinical presentation and clinical course. Diagnosis requires high level of clinical suspicion. Diagnosis is based on good quality imaging, pathology and immunohistochemistry. MPM can be treated with debulking surgery and intra-peritoneal chemotherapy or radiotherapy.

A proposal of Brazilian Society of Surgical Oncology (BSSO/SBCO) for standardizing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

Cytoreductive surgery plus hypertermic intraperitoneal chemotherapy has emerged as a major comprehensive treatment of peritoneal malignancies and is currently the standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome as well as malignant peritoneal mesothelioma. Unfortunately, there are some worldwide variations of the cytoreductive surgery and hypertermic intraperitoneal chemotherapy techniques since no single technique has so far demonstrated its superiority over the others. Therefore, standardization of practices might enhance better comparisons between outcomes. In these settings, the Brazilian Society of Surgical Oncology considered it important to present a proposal for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil, with a special focus on producing homogeneous data for the developing Brazilian register for peritoneal surface malignancies.

Malignant Peritoneal Mesothelioma Presenting With Shortness of Breath and Chest Pain

Malignant Peritoneal Mesothelioma Presenting With Shortness of Breath and Chest Pain

Diffuse peritoneal mesothelioma: A case series of 62 patients including paraoccupational exposures to chrysotile asbestos.

Diffuse peritoneal malignant mesothelioma (DPM) is caused by exposure to asbestos. The medical literature has linked DPM primarily to high levels of asbestos exposure, in particular amosite. Controversy persists as to whether chrysotile is capable of causing DPM, especially when exposures are paraoccupational. Sixty-two subjects (51 men, 11 women) with DPM were reviewed in medical-legal consultation with deposition and product identification evidence. All had pathologically confirmed DPM. Most were exposed to both amphibole and chrysotile, but chrysotile alone was documented in 14/62 (26%) cases. A total of 7/14 (50%) cases of the paraoccupational exposures were to chrysotile alone. Women were younger than men as were those with paraoccupational versus those with occupational exposure. The mean duration of exposure for all cases was 17.9 ± 10 years and latency from time of first exposure was 45.9 + 11.6 years. DPM occurs with both occupational and paraoccupational exposures to asbestos and may be seen in paraoccupational exposures to chrysotile asbestos.

Recent advances in diagnosis and treatment of malignant peritoneal mesothelioma

Recent advances in diagnosis and treatment of malignant peritoneal mesothelioma

Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy.

This report aims to describe preliminary results concerning secondary resectability after bidirectional chemotherapy for initially unresectable malignant peritoneal mesothelioma (MPM). Between January 2013 and January 2016, 20 consecutive patients treated for diffuse MPM not suitable for upfront surgery received bidirectional chemotherapy associating intraperitoneal and systemic chemotherapy. Evaluation of the response to chemotherapy was assessed clinically and by laparoscopy. The median peritoneal cancer index (PCI) score at staging laparoscopy was 27 (range 15-39). Altogether, 118 intraperitoneal chemotherapy cycles were administered without any specific adverse catheter-related event. Concerning tolerance, 85% of the patients experienced no pain or mild pain during chemotherapy administration. The clinical response rate was 60% after a median of three chemotherapy cycles. At laparoscopic reevaluation, the median PCI was 18 (range 0-35), and a secondary resectability was considered for 55% of the patients. Complete cytoreduction surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) was finally achieved for 10 patients (50%), with a median intraoperative PCI score of 14 (range 6-30). After a median follow-up period of 18months, the 2-year overall survival rate was 83.3% for the patients treated by CRS followed by HIPEC and 44% for the patients treated by bidirectional chemotherapy. Bidirectional chemotherapy is a promising, well-tolerated treatment capable of increasing the resection rate for selected patients with diffuse MPM initially considered as unresectable or borderline resectable. For patients with definitively unresectable disease, bidirectional chemotherapy achieves a higher clinical response rate.