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Liang XL, Su YD, Li XB, Fu YB, Ma R, Yang R, Wu HL, Cui YR, Li Y. Prognostic Factors of Long-Term Survival and Conditional Survival Analysis in MPM Patients Treated with CRS+HIPEC: A Retrospective Study of Two Centers. Ann Surg Oncol 2025; 32:2912-2922. [PMID: 39538101 DOI: 10.1245/s10434-024-16485-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVES This study was designed to explore the survival benefit factors of malignant peritoneal mesothelioma (MPM) patients after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and to make dynamic survival prediction by conditional survival (CS). METHODS Data of 212 patients with MPM who underwent CRS+HIPEC were retrospectively analyzed. Patients were divided into long-term survival (LTS) group (≥48.0 months) and short-term survival (STS) group (≤16.0 months) according to OS. Conditional survival is the probability of surviving y years after already survived for x years. Univariate and multivariate analyses were performed to explore the favorable factors of LTS. Conditional survival and Kaplan-Meier were applied to assess the postoperative survival probability. RESULTS Ninety patients were enrolled: 53 (58.9%) were LTS, and 37 (41.1%) were STS. Univariate analysis revealed 14 meaningful factors (P < 0.05): age, surgery history, Karnofsky performance status, pathological types, tumor vascular emboli, lymphatic metastasis, Ki-67 index, preoperative CA125 level, peritoneal cancer index (PCI), completeness of cytoreduction, bleeding, red blood cell (RBC) transfusion, ascites, and severe adverse events (SAEs). Multivariate analysis identified that PCI ≤ 20, less RBC transfusion and no SAEs were independent prognostic factors for LTS. Five-year CS increased from 27% at 0 years to 84% at 4 years with the increasing number of survival years. The survival curve flattens at postoperative 5 years. CONCLUSIONS The key factors in CRS+HIPEC for MPM patients to achieve LTS are lower tumor burden, less intraoperative RBC transfusion, and prevention of SAEs. Malignant peritoneal mesothelioma patients demonstrated a substantial increase in CS over time. Some patients may achieve clinical cure 5 years after surgery.
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Affiliation(s)
- Xin-Li Liang
- Department of Surgical Oncology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yan-Dong Su
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Xin-Bao Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yu-Bin Fu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Ru Ma
- Department of Surgical Oncology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Rui Yang
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - He-Liang Wu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yu-Run Cui
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yan Li
- Department of Surgical Oncology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
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Tang F, Cui Y, Gao Y. Diagnosis and treatment of malignant retroperitoneal mesothelioma: A case report. Medicine (Baltimore) 2024; 103:e37985. [PMID: 38669368 PMCID: PMC11049770 DOI: 10.1097/md.0000000000037985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 04/02/2024] [Indexed: 04/28/2024] Open
Abstract
RATIONALE Malignant peritoneal mesothelioma (MPM) is a rare clinical disease. Although there are several reports describing intraperitoneal mesothelioma of the lung, liver, and intestine, retroperitoneal mesothelioma is, to our knowledge, very rare and rarely reported. In recent years, our best clinical protocols for the treatment and diagnosis of retroperitoneal mesothelioma have not been proven and the diagnosis and treatment are challenging. PATIENT CONCERNS A 37-year-old Chinese woman complained of bilateral low back pain for a month, with obvious symptoms of low back pain on the left side. To treat low back pain, retroperitoneal masses were found during physical examination. The patient consulted a urological specialist for further treatment. DIAGNOSIS After the operation, pathological biopsy confirmed retroperitoneal epithelioid diffuse mesothelioma. INTERVENTIONS After exclusion of surgical contraindications, the patient underwent laparoscopic retroperitoneal lesion resection under tracheal intubation and general anesthesia, and the operation was successful. OUTCOMES On the tenth day after surgery, the patient vital signs were stable, and he was discharged. LESSONS Patients with malignant peritoneal mesothelioma may have no typical clinical symptoms, and the diagnosis is based on pathological and immunohistochemical examination. In selected patients, surgical cell reduction and intraoperative intraperitoneal heat chemotherapy have become the first choice of treatment, which can achieve ideal therapeutic effects and prolong survival.
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Affiliation(s)
- Feihu Tang
- Department of Clinical Medicine, Shandong Second Medical University, Weifang City, Shandong, China
| | - Yong Cui
- Department of Clinical Medicine, Shandong Second Medical University, Weifang City, Shandong, China
| | - Yuan Gao
- Department of Urinary Surgery, Weifang People’s Hospital, No.151 Guangwen Street, Weifang City, Shandong, China
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Deban M, Taqi K, Knapp GC, Soucisse M, Curry M, Sidéris L, Dubé P, Khaldi MA, Jedrzejko N, Porter G, Giacomantonio C, Hamilton T, MacNeill A, Mack L, Bouchard-Fortier A. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma: Canadian practices and outcomes. J Surg Oncol 2023; 128:595-603. [PMID: 37249154 DOI: 10.1002/jso.27301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 03/26/2023] [Accepted: 04/18/2023] [Indexed: 05/31/2023]
Abstract
INTRODUCTION Peritoneal mesothelioma (PM) is a rare malignancy originating from the peritoneal lining. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is the standard-of-care for patients with isolated PM. Due to a paucity of prospective data there are several different HIPEC protocols. The aims of this study are to describe the CRS and HIPEC protocols for PM and patient outcomes across Canada. METHODS A multicenter retrospective study was performed on patients diagnosed and treated for PM with CRS and HIPEC in four major peritoneal disease centers in Canada between 2000 and 2021. Data on patient characteristics, treatment patterns, postoperative morbidity, recurrence, and survival were collected. RESULTS A total of 72 patients were identified. Mean age was 52 years (17-75) and 37.5% were male. Epithelioid (70.1%) and multicystic (13%) mesothelioma were the most common subtypes. Twenty-one patients (30%) were treated with neoadjuvant chemotherapy. CRS and HIPEC was performed in 64 patients (91.4%). Of these, the mean PCI was 22 (2-39) and cisplatin+doxorubicin was the most common HIPEC regimen (n = 33, 51.6%). A semi-closed coliseum technique was used in 68.8% of HIPECs and the mean duration of surgery was 486 min (90-1052). Clavien-Dindo III or IV complications occurred in 12 patients (16.9%). With a median follow-up of 24 months (0.2-104.4), we found a 5-year overall survival of 61% and a 5-year recurrence-free survival of 35%. CONCLUSION CRS and HIPEC is a safe and effective treatment modality for well-selected patients with PM, with some achieving prolonged survival.
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Affiliation(s)
- Melina Deban
- Tom Baker Cancer Center, Calgary, Alberta, Canada
| | - Kadhim Taqi
- Vancouver General Hospital, Vancouver, British Columbia, Canada
| | | | | | - Matt Curry
- QE II Health Sciences Center, Halifax, Nova Scotia, Canada
| | - Lucas Sidéris
- Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
| | - Pierre Dubé
- Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
| | | | | | - Geoff Porter
- QE II Health Sciences Center, Halifax, Nova Scotia, Canada
| | | | - Trevor Hamilton
- Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Andrea MacNeill
- Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Lloyd Mack
- Tom Baker Cancer Center, Calgary, Alberta, Canada
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van Kooten JP, de Gooijer CJ, von der Thüsen JH, Brandt-Kerkhof ARM, Albers AGJ, Lahaye MJ, Monkhorst K, Burgers JA, Aerts JGJV, Verhoef C, Madsen EVE. Impact of centralization of care for malignant peritoneal mesothelioma: A historical cohort study from the Dutch mesothelioma expert centers. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:611-618. [PMID: 36610896 DOI: 10.1016/j.ejso.2022.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 09/07/2022] [Accepted: 10/07/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer that has a poor prognosis. An earlier population-based study found that the majority of Dutch patients do not receive anti-cancer treatment. In 2015, Dutch Malignant Mesothelioma care was centralized in two expert centers. We reviewed treatment patterns at these centers, to assess the impact of centralization of MPM care in the Netherlands. METHODS Data from all patients referred to the Dutch MPM expert centers from 2014 to 2020, were retrospectively collected. Descriptive statistics regarding referrals, patient and tumor characteristics, and treatment patterns were provided. Population-based incidence rates were provided by the Netherlands Cancer Registry. RESULTS From 2014 to 2020, 78 patients were referred to the Dutch Mesothelioma expert centers, of whom 32 were female (41%). From 2014 to 2017, 27 patients were referred, whereas 51 patients were referred from 2018 to 2020. This represents about 24% and 61% of the estimated population incidence, respectively. Treatment patterns were comparable between both periods. Between 2014 and 2018, 33% of patients underwent surgery, 44% systemic therapy, and 22% received best supportive care (BSC), while this was 29%, 37%, and 33% respectively from 2018 to 2020. CONCLUSION Centralization of care for patients with MPM resulted in an increase of annual referrals to the Dutch mesothelioma expert centers. While population-based incidence did not change during the study period, the absolute number of patients receiving treatment at our centers did increase. This might be considered a first important step towards better treatment for patients with this fatal disease.
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Affiliation(s)
- Job P van Kooten
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
| | - Cornedine J de Gooijer
- Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | - Alexandra R M Brandt-Kerkhof
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Arend G J Albers
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Max J Lahaye
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Kim Monkhorst
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Jacobus A Burgers
- Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Joachim G J V Aerts
- Department of Pulmonary Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Eva V E Madsen
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
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Rouhi AD, Choudhury RA, Hoeltzel GD, Yule A, Williams NN, Dumon KR, Karakousis GC. Delayed CRS-HIPEC Is Associated with Decreased Survival in Patients with Malignant Peritoneal Mesothelioma: A Markov Decision Analysis. J Gastrointest Surg 2022; 27:995-997. [PMID: 36443555 DOI: 10.1007/s11605-022-05540-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 11/01/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Armaun D Rouhi
- Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, 4th Floor Silverstein, PA, 19104, Philadelphia, USA
| | | | - Gerard D Hoeltzel
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Arthur Yule
- Department of Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Noel N Williams
- Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, 4th Floor Silverstein, PA, 19104, Philadelphia, USA
| | - Kristoffel R Dumon
- Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, 4th Floor Silverstein, PA, 19104, Philadelphia, USA.
| | - Giorgos C Karakousis
- Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, 4th Floor Silverstein, PA, 19104, Philadelphia, USA
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Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma—A 3-D In Vitro Study. Int J Mol Sci 2022; 23:ijms23137293. [PMID: 35806313 PMCID: PMC9267014 DOI: 10.3390/ijms23137293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/24/2022] [Accepted: 06/28/2022] [Indexed: 11/16/2022] Open
Abstract
Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.
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Chandramohan A, Shah N, Thrower A, Carr NJ, Mittal R, Mohamed F, Moran B. Communicating imaging findings in peritoneal mesothelioma: the impact of 'PAUSE' on surgical decision-making. Insights Imaging 2021; 12:174. [PMID: 34817720 PMCID: PMC8613330 DOI: 10.1186/s13244-021-01118-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 10/27/2021] [Indexed: 12/26/2022] Open
Abstract
The peritoneal cavity is the second commonest site of mesothelioma after the pleural cavity. There are five histological types of peritoneal mesothelioma with variable symptomatology, clinical presentation and prognosis. Cystic mesothelioma is a borderline malignant neoplasm with a favourable prognosis, well-differentiated papillary mesothelioma is generally a low-grade malignancy, and all other varieties such as epithelioid, sarcomatoid and biphasic mesothelioma are highly malignant types of peritoneal mesothelioma with poor prognosis. Malignant peritoneal mesothelioma was considered inevitably fatal prior to the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in selected cases where long-term survival and cure could be achieved. However, the survival benefits following CRS and HIPEC mainly depend on completeness of cytoreduction, which come at the cost of high morbidity and potential mortality. Using the acronym 'PAUSE', we aimed at describing the key imaging findings that impact surgical decision-making in patients with peritoneal mesothelioma. PAUSE stands for peritoneal cancer index, ascites and abdominal wall disease, unfavourable sites of involvement, small bowel and mesenteric disease and extraperitoneal disease. Reporting components of 'PAUSE' is crucial for patient selection. Despite limitations of CT in accurately depicting the volume of disease, describing findings in terms of PAUSE plays an important role in excluding patients who might not benefit from CRS and HIPEC.
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Affiliation(s)
| | - Nehal Shah
- Department of Radiology, Basingstoke Hospital, Aldermaston Road, Basingstoke, RG24 9NA, UK
| | - Andrew Thrower
- Department of Radiology, Basingstoke Hospital, Aldermaston Road, Basingstoke, RG24 9NA, UK
| | - Norman John Carr
- Peritoneal Malignancy Institute, Basingstoke Hospital, Aldermaston Road, Basingstoke, RG24 9NA, UK
| | - Rohin Mittal
- Christian Medical College, Vellore, 632004, India
| | - Faheez Mohamed
- Peritoneal Malignancy Institute, Basingstoke Hospital, Aldermaston Road, Basingstoke, RG24 9NA, UK
| | - Brendan Moran
- Peritoneal Malignancy Institute, Basingstoke Hospital, Aldermaston Road, Basingstoke, RG24 9NA, UK
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Ray MD, Dhall K. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the management of peritoneal surface malignancies - An evidence-based review. Curr Probl Cancer 2021; 45:100737. [PMID: 34116836 DOI: 10.1016/j.currproblcancer.2021.100737] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 02/27/2021] [Accepted: 03/15/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Traditionally, peritoneal surface malignancies (PSM) were considered terminal diseases because of their advanced nature, therefore, systemic chemotherapy was given with palliative intent only. As a result, very poor survival outcomes were observed. But with the introduction of complete Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC), the scenario has changed dramatically. METHODOLOGY An objective electronic database search was performed in Pubmed, NLM Catalog, Google scholar, Bookshelf, and Pubmed Central published in the time period from 2000 till 2020. All the randomized studies were included. In the absence of randomized studies, both prospective and retrospective studies were included. The outcomes of HIPEC were measured in terms of median survival, disease-free survival, overall survival, complications and drug toxicities. RESULTS CRS and HIPEC are considered the standard of care for PMP and MPM even in the absence of level 1 evidence due to lack of an effective alternative treatment. In colorectal and gastric cancer, several phase-three trials are showing overall survival benefit in selected cases while there is a prophylactic and palliative role of HIPEC in gastric cancer. Three reported phase 3 trials showed positive results in ovarian cancer. In peritoneal sarcomatosis, the role of HIPEC is yet to be proven. CONCLUSION The patient selection is the key to the successful outcomes after HIPEC. HIPEC should be performed by the experienced surgeons in specialized centres with a strong critical care and intensive care support to reduce the morbidity and mortality. Ongoing trials and future directions will prove to be an indispensable arm in the oncological armamentarium.
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Affiliation(s)
- Mukur Dipi Ray
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Kunal Dhall
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.
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Guaglio M, Baratti D, Kusamura S, Reis ACV, Montenovo M, Bartolini V, Battaglia L, Deraco M. Impact of Previous Gynecologic Surgical Procedures on Outcomes of Non-Gynecologic Peritoneal Malignancies Mimicking Ovarian Cancer: Less Is More? Ann Surg Oncol 2021; 28:2899-2908. [PMID: 33641011 DOI: 10.1245/s10434-021-09587-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 01/02/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Non-gynecologic rare peritoneal surface malignancies (PSMs) often are misdiagnosed as disseminated ovarian cancer and initially treated by gynecologic surgeons. This study aimed to assess whether these previous maneuvers (i.e., full surgical staging and/or cytoreductive attempts) affect outcomes after the definitive surgery performed in a tertiary center. METHODS The study reviewed 298 women affected by non-gynecologic PSM who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after previous gynecologic surgery. Prior surgery was categorized as limited surgery (pLS: abdominal exploration with biopsy plus adnexectomy and/or appendectomy) or extended surgery (pES: full surgical staging or cytoreductive attempts including hysterectomy with bilateral salpingo-oophorectomy). RESULTS Of the 298 patients, 143 had pLS and 153 had pES. Morbidity was similar between the groups (P = 0.143), but the pES group had more severe urinary tract injuries (19 vs. 3; P < 0.001), longer operating time (585.9 vs. 506.7; P = 0.027), and more patients needing more than two anastomoses (41 vs. 26; P = 0.033). Age older than 55 years (odds ratio [OR] 2.42; P = 0.009) and number of anastomoses (OR 3.17; P = 0.002) correlated with severe morbidity; pES correlated with urinary tract grades 3 and 4 injuries (OR 7.9; P = 0.001). The 5-year cumulative incidence of locoregional relapse was significantly higher in the pES group (0.41 vs. 0.27; P = 0.012; median follow-up period, 69 months). The multivariate analysis identified a Peritoneal Carcinomatosis Index (PCI) higher than 20 and pES as independent risk factors. CONCLUSION For women undergoing CRS±HIPEC for non-gynecologic PSM, the risk for locoregional relapse and severe postsurgical urinary tract complications is increased by pES. Therefore, prior full surgical staging or cytoreductive attempts without definitive gynecologic histology should be avoided. Prophylactic ureteral stenting and stricter oncologic follow-up assessment must be considered in this scenario.
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Affiliation(s)
- Marcello Guaglio
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Dario Baratti
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Shigeki Kusamura
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Arthur C V Reis
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.,Fellow of European School of PeritonealSurface Oncology (ESPSO), Department of Gastrointestinal Surgery, Irmandade Santa Casa de Misericórdia de São José Dos Campos, São Paulo, Brazil
| | - Matteo Montenovo
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Valentina Bartolini
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Luigi Battaglia
- Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marcello Deraco
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Elghali MA, Bourigua R, Belaid I, Nasri S, Mestiri S, Yaacoub S, Makni A, Letaief R. Prolonged survival with systemic chemotherapy in an advanced malignant mesothelioma: A case report. Rare Tumors 2021; 13:2036361320984527. [PMID: 33613924 PMCID: PMC7874336 DOI: 10.1177/2036361320984527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 12/07/2020] [Indexed: 11/16/2022] Open
Abstract
Peritoneal mesotheliomas are very rare tumors. Their prognosis is poor, average survival does not exceed 1 year after peritoneal cytoreduction. Systemic chemotherapy is considered to have no proven value in the management of peritoneal mesotheliomas. Objective responses with systemic chemotherapy are very rare. We report here a case of an advanced peritoneal mesothelioma which achieved an unexpected partial response with chemotherapy, allowing the patient to have a right colectomy. The patient was referred to a specialized center on HIPEC, but taking in account the long awaiting interval, the HIPEC was judged to be inefficient and then the poursuit of 6 cycles of systemic chemotherapy was decided. The patient is still alive without any symptom and with a good performance status at 59 months after diagnosis. Throughout our case, we provide an encouraging evidence of the role of initial systemic chemotherapy in the downstaging of initially unresectable primary malignant mesothelioma and in the improvement of overall survival.
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Affiliation(s)
- Mohamed Amine Elghali
- Department of Digestive Surgery, University of Sousse, Faculty of Medicine, Farhat Hached University Hospital, Sousse, Tunisia
| | - Rym Bourigua
- Department of Medical Oncology, University of Sousse, Faculty of Medicine, Farhat Hached University Hospital, Sousse, Tunisia
| | - Imtinene Belaid
- Department of Medical Oncology, University of Sousse, Faculty of Medicine, Farhat Hached University Hospital, Sousse, Tunisia
| | - Salsabil Nasri
- Department of Digestive Surgery, University of Sousse, Faculty of Medicine, Farhat Hached University Hospital, Sousse, Tunisia
| | - Sara Mestiri
- Department of Pathology, University of Sousse, Faculty of Medicine, Farhat Hached University Hospital, Sousse, Tunisia
| | - Sara Yaacoub
- Department of Pathology, University of Sousse, Faculty of Medicine, Farhat Hached University Hospital, Sousse, Tunisia
| | - Amine Makni
- Department of Digestive Surgery, University of Tunis, Faculty of Medicine, La Rabta University Hospital, Tunis, Tunisia
| | - Rached Letaief
- Department of Digestive Surgery, University of Sousse, Faculty of Medicine, Farhat Hached University Hospital, Sousse, Tunisia
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Ray MD, Dhall K. Where Does HIPEC Stand: An Evidence Based Review. MULTIDISCIPLINARY APPROACH TO SURGICAL ONCOLOGY PATIENTS 2021:349-358. [DOI: 10.1007/978-981-15-7699-7_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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12
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Brandl A, Westbrook S, Nunn S, Arbuthnot-Smith E, Mulsow J, Youssef H, Carr N, Tzivanakis A, Dayal S, Mohamed F, Moran BJ, Cecil T. Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting. BJS Open 2020; 4:260-267. [PMID: 32003132 PMCID: PMC7093780 DOI: 10.1002/bjs5.50256] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 11/29/2019] [Indexed: 12/21/2022] Open
Abstract
Background Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video‐conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. Methods Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video‐conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. Results A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien–Dindo grade I–II complications occurred in 16 patients; there was no grade III–IV morbidity or 30‐day in‐hospital mortality. The median follow‐up for the whole cohort was 18·7 months, and the 2‐year survival rate from time of first review at the national PM MDT was 68·3 per cent. Conclusion The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection.
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Affiliation(s)
- A Brandl
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - S Westbrook
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - S Nunn
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - E Arbuthnot-Smith
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - J Mulsow
- National Centre for Peritoneal Malignancy, Mater Misericordiae University Hospital, Dublin, Ireland
| | - H Youssef
- Good Hope Hospital, Heart of England NHS Foundation Trust, Birmingham, UK
| | - N Carr
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - A Tzivanakis
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - S Dayal
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - F Mohamed
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - B J Moran
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - T Cecil
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
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Establishment and characterization of a new malignant peritoneal mesothelioma cell line, KOG-1, from the ascitic fluid of a patient with pemetrexed chemotherapy resistance. Hum Cell 2019; 33:272-282. [PMID: 31583526 DOI: 10.1007/s13577-019-00286-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 09/24/2019] [Indexed: 10/25/2022]
Abstract
Malignant peritoneal mesothelioma (MPeM) is a rare and aggressive form of malignant mesothelioma. Sufficient biological tools for studying the functional characteristics of this cancer have not been developed. Therefore, in this study, a novel human cancer cell line, KOG-1, was established from ascites fluids isolated from a 39-year-old Japanese woman with pemetrexed-resistant MPeM. Cells were dendritic or linear immediately after thawing, showed a jigsaw puzzle-like and spindle arrangement during growth, and formed monolayers without contact inhibition in two-dimensional (2D) culture. The population doubling time was 13.7 h. Karyotypic and molecular genetic analyses showed that chromosome numbers ranged from 62 to 142, with a peak of 73 with complicated copy number alterations. No germline BAP1 pathogenic variant was detected. Cells expressed various tumor markers of mesothelioma, such as calretinin, podoplanin, and Wilms tumor 1 (WT-1). Drug sensitivity and resistance testing with a set of 36 drugs using 2D and three-dimensional (3D) culture models demonstrated that KOG-1 cells showed high and low sensitivity to pemetrexed under 2D and 3D culture conditions, respectively, whereas control ovarian cancer cell lines showed low sensitivity to pemetrexed under both culture conditions. This newly established cell line will be a valuable biological resource to expand the feasibility of functional studies as well as drug testing for potential therapeutic purposes in MPeM.
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Jiang Y, Mei Z, Cao H, Li S, Xu H, Qiu H, Liu Y. Meningeal metastasis of a malignant peritoneal mesothelioma: A case report and literature review. Cancer Biol Ther 2019; 20:1409-1415. [PMID: 31411522 DOI: 10.1080/15384047.2019.1647053] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.
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Affiliation(s)
- Yaofei Jiang
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University , Wuhan , China
| | - Zijie Mei
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University , Wuhan , China
| | - Hong Cao
- Department of Pathology, Zhongnan Hospital of Wuhan University , Wuhan , Hubei , China
| | - Sirui Li
- Department of Radiology, Zhongnan Hospital of Wuhan University , Wuhan , Hubei , China
| | - Haibo Xu
- Department of Radiology, Zhongnan Hospital of Wuhan University , Wuhan , Hubei , China
| | - Hui Qiu
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University , Wuhan , China
| | - Yu Liu
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University , Wuhan , China
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15
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Letica-Kriegel AS, Leinwand JC, Sonett JR, Gorenstein LA, Taub RN, Chabot JA, Kluger MD. 50 Patients with Malignant Mesothelioma of Both the Pleura and Peritoneum: A Single-Institution Experience. Ann Surg Oncol 2019; 27:205-213. [DOI: 10.1245/s10434-019-07409-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Indexed: 11/18/2022]
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16
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Kusamura S, González-Moreno S, Nizri E, Baratti D, Guadagni S, Guaglio M, Battaglia L, Deraco M. Learning Curve, Training Program, and Monitorization of Surgical Performance of Peritoneal Surface Malignancies Centers. Surg Oncol Clin N Am 2018; 27:507-517. [PMID: 29935686 DOI: 10.1016/j.soc.2018.02.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is a complex procedure with high cost and significant morbidity and mortality. The associated learning curve is steep and could reliably be evaluated using specific statistics. Risk-adjusted sequential probability ratio test is an effective and robust method to monitor surgical performance in the learning and audit phase of a peritoneal surface malignancies center development. The most critical factor associated with surgical performance is mentoring of the trainee by an expert. A well-structured tutor-based training program has been implemented in Europe. This initiative will improve the standardization of the combined procedure and improve quality of services across the continent.
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Affiliation(s)
- Shigeki Kusamura
- Peritoneal Surface Malignancies unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, Milano, Milan cap 20133, Italy
| | | | - Eran Nizri
- Department of General Surgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Weizmann Street 6, Tel Aviv, Israel
| | - Dario Baratti
- Peritoneal Surface Malignancies unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, Milano, Milan cap 20133, Italy
| | - Stefano Guadagni
- Department of Biotechnological and Applied Clinical Sciences, Università degli Studi dell'Aquila, Via Giovanni di Vincenzo, 16/B, L'Aquila, Italy
| | - Marcello Guaglio
- Peritoneal Surface Malignancies unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, Milano, Milan cap 20133, Italy
| | - Luigi Battaglia
- Colorectal Cancer unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, Milano, MI, cap 20133, Italy
| | - Marcello Deraco
- Peritoneal Surface Malignancies unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, Milano, Milan cap 20133, Italy.
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17
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Brandl A, Pratschke J, Rau B. Chirurgisch-onkologische Therapie primärer und sekundärer peritonealer Neoplasien. Eur Surg 2018. [DOI: 10.1007/s10353-018-0553-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Boussios S, Moschetta M, Karathanasi A, Tsiouris AK, Kanellos FS, Tatsi K, Katsanos KH, Christodoulou DK. Malignant peritoneal mesothelioma: clinical aspects, and therapeutic perspectives. Ann Gastroenterol 2018; 31:659-669. [PMID: 30386115 PMCID: PMC6191875 DOI: 10.20524/aog.2018.0305] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 07/18/2018] [Indexed: 12/11/2022] Open
Abstract
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.
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Affiliation(s)
- Stergios Boussios
- Medway NHS Foundation Trust, Kent, UK (Stergios Boussios, Afroditi Karathanasi)
| | - Michele Moschetta
- Drug Development Unit, Sarah Cannon Research Institute, London, UK (Michele Moschetta)
| | | | - Alexandros K Tsiouris
- Department of Biological Applications & Technology, University of Ioannina, Ioannina, Greece (Alexandros K. Tsiouris, Foivos S. Kanellos)
| | - Foivos S Kanellos
- Department of Biological Applications & Technology, University of Ioannina, Ioannina, Greece (Alexandros K. Tsiouris, Foivos S. Kanellos)
| | - Konstantina Tatsi
- Gynecology Unit, General Hospital "G. Hatzikosta", Ioannina, Greece (Konstantina Tatsi)
| | - Konstantinos H Katsanos
- Department of Gastroenterology, University Hospital of Ioannina, Faculty of Medicine, School of Health Sciences, University of Ioannina, Greece (Konstantinos H. Katsanos, Dimitrios K. Christodoulou)
| | - Dimitrios K Christodoulou
- Department of Gastroenterology, University Hospital of Ioannina, Faculty of Medicine, School of Health Sciences, University of Ioannina, Greece (Konstantinos H. Katsanos, Dimitrios K. Christodoulou)
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Kindler HL. The Challenge of Defining Treatment Standards for a Rare Disease: Malignant Peritoneal Mesothelioma. J Oncol Pract 2018; 12:936-937. [PMID: 27858567 DOI: 10.1200/jop.2016.016576] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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20
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Bruno F, Baratti D, Martinetti A, Morelli D, Sottotetti E, Bonini C, Guaglio M, Kusamura S, Deraco M. Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study. Eur J Surg Oncol 2018; 44:792-798. [DOI: 10.1016/j.ejso.2018.02.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 02/06/2018] [Indexed: 02/06/2023] Open
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Badrudin D, Sideris L, Perrault-Mercier C, Hubert J, Leblond FA, Dubé P. Comparison of open and closed abdomen techniques for the delivery of intraperitoneal pemetrexed using a murine model. J Surg Oncol 2018; 117:1318-1322. [PMID: 29355970 DOI: 10.1002/jso.24960] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Revised: 10/24/2017] [Accepted: 11/30/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND OBJECTIVES Pemetrexed is an appealing agent to use for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the optimal method of pemetrexed delivery still remains undefined. Using a murine model, we compared the use of open and closed abdomen techniques on the absorption of intraperitoneal (IP) pemetrexed in different compartments. METHODS Eleven Sprague-Dawley rats were submitted to a fixed dose of IP pemetrexed (1000 mg/m2 ) at a perfusion temperature of 40°C during 25 min according to two techniques: open and closed. At the end of perfusion, samples in different compartments were harvested and the concentrations of pemetrexed were measured by high performance liquid chromatography. RESULTS Absorption of IP pemetrexed in portal and systemic blood was significantly higher using the open compared to the closed abdomen technique (93.17 vs 52.50 µg/mL, P < 0.001) and (76.26 vs 51.65 µg/mL, P < 0.001), respectively. No difference was found between the two techniques on the peritoneal tissue concentration of pemetrexed (18.07 vs 19.17 µg/g, P = 0.51). CONCLUSION Peritoneal absorption of pemetrexed is not modified by the use of either technique. However, systemic concentrations of pemetrexed increased using the open technique, suggesting it could increase systemic toxicity.
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Affiliation(s)
- David Badrudin
- Maisonneuve-Rosemont Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
| | - Lucas Sideris
- Maisonneuve-Rosemont Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
| | - Camille Perrault-Mercier
- Maisonneuve-Rosemont Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
| | - Julien Hubert
- Maisonneuve-Rosemont Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
| | - François A Leblond
- Maisonneuve-Rosemont Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
| | - Pierre Dubé
- Maisonneuve-Rosemont Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
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Cytoreductive Surgery and HIPEC in the First-Line and Interval Time Points of Advanced Epithelial Ovarian Cancer. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2017. [DOI: 10.1007/s40944-017-0148-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Fujimoto E, Kijima T, Kuribayashi K, Negi Y, Kanemura S, Mikami K, Doi H, Kitajima K, Nakano T. First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma. Expert Rev Anticancer Ther 2017; 17:865-872. [PMID: 28594258 DOI: 10.1080/14737140.2017.1340157] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM. RESEARCH DESIGN AND METHODS Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent 18F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment. RESULTS Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively. Wet- type MPeM had significantly longer survival (40.9 months median) than other clinical types (15.5 months) (P = 0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5-16.77). CONCLUSIONS Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.
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Affiliation(s)
- Eriko Fujimoto
- a Division of Respiratory Medicine, Department of Internal Medicine , Hyogo College of Medicine , Hyogo , Japan
| | - Takashi Kijima
- a Division of Respiratory Medicine, Department of Internal Medicine , Hyogo College of Medicine , Hyogo , Japan
| | - Kozo Kuribayashi
- a Division of Respiratory Medicine, Department of Internal Medicine , Hyogo College of Medicine , Hyogo , Japan
| | - Yoshiki Negi
- a Division of Respiratory Medicine, Department of Internal Medicine , Hyogo College of Medicine , Hyogo , Japan
| | - Shingo Kanemura
- a Division of Respiratory Medicine, Department of Internal Medicine , Hyogo College of Medicine , Hyogo , Japan
| | - Koji Mikami
- a Division of Respiratory Medicine, Department of Internal Medicine , Hyogo College of Medicine , Hyogo , Japan
| | - Hiroshi Doi
- b Department of Radiology , Hyogo College of Medicine , Hyogo , Japan
| | - Kazuhiro Kitajima
- b Department of Radiology , Hyogo College of Medicine , Hyogo , Japan
| | - Takashi Nakano
- a Division of Respiratory Medicine, Department of Internal Medicine , Hyogo College of Medicine , Hyogo , Japan
- c Center for Respiratory Diseases , Otemae Hospital , Osaka , Japan
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Chandramohan A, Thrower A, Shah N, Mohamed F. Radiological predictors of complete cytoreduction in 59 patients with peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a UK referral centre. Br J Radiol 2017; 90:20170361. [PMID: 28830230 DOI: 10.1259/bjr.20170361] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To assess the imaging features of peritoneal mesothelioma and identify key anatomical sites that aid patient selection for complete cytoreduction. METHODS Pre-operative imaging of 59 (32 males, 27 females) patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for histologically proven peritoneal mesothelioma [36 malignant peritoneal mesothelioma, 23 cystic mesothelioma were reviewed. Imaging findings were correlated with surgical outcome. Best imaging predictors of complete cytoreduction, n = 22 and major tumour debulking, n = 12 were assessed. RESULTS Most patients (88.9%) had diffuse peritoneal disease with mean radiological peritoneal cancer index of 18 ± 12 (range 2-39). Disease in the lesser omentum (n = 10), porta hepatis (n = 8), perigastric area (n = 5), mesentery (n = 25), small bowel (n = 17), hydronephrosis (n = 1), concurrent pleural disease (n = 2), lymph nodes (n = 1) and abdominal wall disease (n = 4) was considered unfavourable. While 78.9% of patients who underwent complete cytoreduction had no disease at unfavourable sites, 75% of those who underwent MTD did have disease at these sites. There was significant difference in the radiological peritoneal cancer index, severity of upper abdominal disease, small bowel and mesenteric involvement between patients who underwent complete cytoreduction and MTD for malignant peritoneal mesothelioma. Complete cytoreduction was not achieved in the presence of a rind of soft tissue around the small bowel (p = 0.016) and was unlikely in the presence of large volume upper abdominal disease (p = 0.06). CONCLUSION Involvement of key anatomical sites such as small bowel serosa and large volume upper abdominal disease reduced the likelihood of achieving complete cytoreduction in patients with malignant peritoneal mesothelioma. Advances in knowledge: Demonstration of small bowel disease and large volume upper abdominal disease on imaging in patients with malignant peritoneal mesothelioma can be used to identify patients who may not benefit from cytoreductive surgery.
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Affiliation(s)
- Anuradha Chandramohan
- 1 Visiting Faculty, Abdominal Imaging Unit, Department of Radiology, MD Anderson Cancer Center, Houston, TX, USA.,2 Associate professor of Radiology, Christian Medical College, Vellore, India
| | - Andrew Thrower
- 3 Consultant Radiologist, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, England
| | - Nehal Shah
- 3 Consultant Radiologist, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, England
| | - Faheez Mohamed
- 4 Consultant Surgeon, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, England
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El-Gamal MI, Anbar HS. Recent advances of pyrrolopyridines derivatives: a patent and literature review. Expert Opin Ther Pat 2017; 27:591-606. [DOI: 10.1080/13543776.2017.1280465] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Mohammed I. El-Gamal
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
- Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt
| | - Hanan S. Anbar
- Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt
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Pharmacokinetics and the effect of heat on intraperitoneal pemetrexed using a murine model. Surg Oncol 2016; 25:435-440. [DOI: 10.1016/j.suronc.2016.05.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 05/12/2016] [Accepted: 05/19/2016] [Indexed: 11/22/2022]
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Spiliotis J, Halkia E, de Bree E. Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy-current perspectives. Curr Oncol 2016; 23:e266-e275. [PMID: 27330364 PMCID: PMC4900847 DOI: 10.3747/co.23.2831] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Peritoneal carcinomatosis (ptc) represents advanced malignant disease and has generally been associated with a grim prognosis. Peritoneal surface malignancy is often the major source of morbidity and mortality; it is of major concern in cancer management. Although ptc is categorized as metastatic disease, it represents a special disease pattern considered to be a locoregional disease limited to the abdominal cavity. The combination of cytoreductive surgery (crs) and intraoperative hyperthermic intraperitoneal chemotherapy (hipec) has successfully been used as locoregional treatment for selected patients with ptc from gastric, colorectal, and ovarian cancer; with mesothelioma; and with pseudomyxoma peritonei. In the prophylactic setting, hipec can also be used to prevent ptc in high-risk patients, and the first results of the "second-look" approach are promising. Patient selection-in which the risks of perioperative morbidity and mortality, which are analogous to those for any other major gastrointestinal surgery, are assessed-is of utmost importance. Those risks have to be weighed against the anticipated survival benefit, which depends mainly on tumour biology, extent of disease, and probability of achieving complete crs. The present review discusses the principles of crs and hipec, the most significant recent clinical data, and current perspectives concerning the application of this treatment modality in various malignancies. Ongoing trials and future directions are noted. It appears that the combination of crs and hipec is an indispensable tool in the oncologist's armamentarium.
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Affiliation(s)
- J. Spiliotis
- 1st Department of Surgery, Metaxa Cancer Institute, Piraeus, Greece
| | - E. Halkia
- Peritoneal Surface Malignancy Unit, iaso General Hospital, Athens, Greece
| | - E. de Bree
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
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Brevet M. Comparative genetics of diffuse malignant mesothelioma tumors of the peritoneumand pleura, with focus on BAP1 expression. Pleura Peritoneum 2016; 1:91-97. [PMID: 30911612 DOI: 10.1515/pp-2016-0007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 05/04/2016] [Indexed: 12/27/2022] Open
Abstract
Malignant mesothelioma (MM) is a malignancy arising from the mesothelial cells lining the thoracic and abdominal serosal cavities. The pleural space is the most commonly affected site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. The different types of mesotheliomas are generally considered as distinct diseases with specific risk factors, therapeutic strategies and prognoses. Epidemiological and clinical differences between pleural and peritoneal MM raise questions about the involvement of different molecular mechanisms. Since the BAP1 gene is involved in the BAP1 cancer syndrome and seems to be a prognostic factor in MM, this review presents an overview of BAP1 alterations in mesothelioma comparing pleural and peritoneal localizations.
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Benedetti S, Nuvoli B, Catalani S, Galati R. Reactive oxygen species a double-edged sword for mesothelioma. Oncotarget 2016; 6:16848-65. [PMID: 26078352 PMCID: PMC4627278 DOI: 10.18632/oncotarget.4253] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 05/29/2015] [Indexed: 12/13/2022] Open
Abstract
It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10-15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display 'asbestos-like' pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review.
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Affiliation(s)
- Serena Benedetti
- Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy
| | - Barbara Nuvoli
- Molecular Medicine Area, Regina Elena National Cancer Institute, Rome, Italy
| | - Simona Catalani
- Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy
| | - Rossella Galati
- Molecular Medicine Area, Regina Elena National Cancer Institute, Rome, Italy
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Abstract
The etiology, gender distribution, pathology, natural history, and treatment options for mesothelioma (MM) differ substantially depending on the site of origin. Peritoneal mesothelioma (MPeM) is a rare disease, comprising only approximately 10% to 15% of the 2,500 cases of MM diagnosed in the United States each year. Patients with MPeM are younger than patients with pleural MM, and a higher proportion, mostly women, are long-term survivors. Most MPeM is caused by asbestos exposure. Germ-line mutations of BAP1 (BRCA associated protein 1) can predispose to MM, uveal melanoma, and potentially other cancers. MPeM can be challenging to diagnose, and cytology is rarely helpful. Review by an experienced pathologist using a panel of at least two positive and two negative immunohistochemical stains is essential. The three major pathologic subtypes are epithelial, sarcomatoid, and biphasic. Most cases are epithelial; the others have a dismal prognosis. Two indolent subtypes of borderline malignant potential-well-differentiated papillary mesothelioma and benign multicystic mesothelioma-are more common in the peritoneum and are treated surgically. In highly selected patients receiving treatment at experienced referral centers, an aggressive locoregional strategy that combines cytoreductive surgery to remove all gross disease and hyperthermic intraperitoneal chemotherapy to treat residual microscopic tumors yields a 3-year survival of 60% and a median survival approaching 5 years, far better than expected from historic controls. This approach also provides durable palliation of malignant ascites in nearly all patients. Pemetrexed is the only U.S. Food and Drug Administration (FDA)-approved systemic chemotherapy for pleural MM. Largely on the basis of data from pharmaceutical registry studies, the activity of pemetrexed-based chemotherapy appears to be similar in pleural MM and MPeM.
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Affiliation(s)
- Hedy Lee Kindler
- From the Gastrointestinal Oncology and Mesothelioma Programs, Section of Hematology/Oncology, University of Chicago, Chicago, IL
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31
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Mogal H, Chouliaras K, Levine EA, Shen P, Votanopoulos KI. Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: review of indications and outcomes. J Gastrointest Oncol 2016; 7:129-42. [PMID: 26941991 DOI: 10.3978/j.issn.2078-6891.2015.131] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment option in selected patients with peritoneal dissemination from a variety of epithelial primaries. Even though a small proportion will be alive and potentially cured at 10 years, the majority will eventually develop recurrent disease. Repeat CRS/HIPEC is a valid consideration in a selected subpopulation of patients with isolated peritoneal recurrence. This review summarizes the data on patient selection, feasibility, limitations and outcomes of repeat CRS/HIPEC.
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Affiliation(s)
- Harveshp Mogal
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Konstantinos Chouliaras
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Edward A Levine
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Perry Shen
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Konstantinos I Votanopoulos
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
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Valdivielso Cortázar E, Martínez Echeverría A, Fernández-Urién I, Llanos Chávarri MC, Vila Costas JJ, Jiménez Pérez FJ. [Peritoneal mesothelioma unmasked by an acute appendicitis]. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 39:217-218. [PMID: 25767003 DOI: 10.1016/j.gastrohep.2015.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/19/2015] [Accepted: 01/21/2015] [Indexed: 06/04/2023]
Affiliation(s)
| | | | | | | | - Juan José Vila Costas
- Servicio de Aparato Digestivo, Complejo Hospitalario de Navarra, Pamplona, Navarra, España
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Borczuk AC, Pei J, Taub RN, Levy B, Nahum O, Chen J, Chen K, Testa JR. Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration. Cancer Biol Ther 2016; 17:328-35. [PMID: 26853494 DOI: 10.1080/15384047.2016.1145850] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
Malignant mesothelioma (MM) is an aggressive tumor arising from mesothelial linings of the serosal cavities. Pleural space is the most common site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. While histologically similar, tumors from these sites are epidemiologically and clinically distinct and their attribution to asbestos exposure differs. We compared DNA array-based findings from 48 epithelioid peritoneal MMs and 41 epithelioid pleural MMs to identify similarities and differences in copy number alterations (CNAs). Losses in 3p (BAP1 gene), 9p (CDKN2A) and 22q (NF2) were seen in tumors from both tumor sites, although CDKN2A and NF2 losses were seen at a higher rate in pleural disease (p<0.01). Overall, regions of copy number gain were more common in peritoneal MM, whereas losses were more common in pleural MM, with regions of loss containing known tumor suppressor genes and regions of gain encompassing genes encoding receptor tyrosine kinase pathway members. Cases with known asbestos causation (n = 32 ) were compared with those linked to radiation exposure (n = 9 ). Deletions in 6q, 14q, 17p and 22q, and gain of 17q were seen in asbestos-associated but not radiation-related cases. As reported in post-radiation sarcoma, gains outnumbered losses in radiation-associated MM. The patterns of genomic imbalances suggest overlapping and distinct molecular pathways in MM of the pleura and peritoneum, and that differences in causation (i.e., asbestos vs. radiation) may account for some of these site-dependent differences.
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Affiliation(s)
- Alain C Borczuk
- a Department of Pathology and Medicine , Weill Cornell Medicine , New York , USA
| | - Jianming Pei
- b Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center , Philadelphia , USA
| | - Robert N Taub
- c Department of Medicine , Division of Hematology and Oncology
| | - Brynn Levy
- d Department of Pathology and Cell Biology , Columbia University Medical Center , New York , USA
| | - Odelia Nahum
- d Department of Pathology and Cell Biology , Columbia University Medical Center , New York , USA
| | - Jinli Chen
- d Department of Pathology and Cell Biology , Columbia University Medical Center , New York , USA
| | - Katherine Chen
- a Department of Pathology and Medicine , Weill Cornell Medicine , New York , USA
| | - Joseph R Testa
- b Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center , Philadelphia , USA
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CT differentiation of malignant peritoneal mesothelioma and tuberculous peritonitis. LA RADIOLOGIA MEDICA 2015; 121:253-60. [DOI: 10.1007/s11547-015-0609-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 11/26/2015] [Indexed: 10/22/2022]
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Aydin N, Sardi A, Milovanov V, Nieroda C, Sittig M, Nunez MF, Jimenez W, Gushchin V. Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma: Experience of a Peritoneal Surface Malignancy Center. Am Surg 2015. [DOI: 10.1177/000313481508101228] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon malignancy, which can be difficult to treat. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have evolved as the treatment of choice when complete cytoreduction is to be achieved. This study reports the outcomes of CRS/HIPEC for peritoneal mesothelioma performed in a center for peritoneal surface malignancy. A retrospective analysis of a prospective database of 389 CRS/ HIPEC procedures identified 23 patients who underwent CRS/HIPEC for DMPM from 1999 to 2014. Gender, age at diagnosis, age at surgery, previous surgeries, follow-up time, peritoneal cancer index (PCI) score, completeness of cytoreduction (CC), pathology, and overall survival (OS) were analyzed. The univariate analysis was used to determine the prognostic value of age, gender, neoadjuvant chemotherapy, histopathology of the tumor, PCI, CC, and lymph node status on survival. Mean follow-up time from surgery was 31 months (range = 0.5–124). The median PCI score was 28, and 77 per cent had PCI ≥20. CC 0–1 was achieved in 65 per cent of cases. One- and 5-year actuarial OS rates from diagnosis were 86 per cent and 60 per cent, respectively. One- and 5-year actuarial OS from HIPEC was 70 per cent and 64 per cent, respectively. The univariate analysis showed that the CC was the only significant prognostic factor. Patients with DMPM may achieve long-term survival when treated with CRS/HIPEC. The CC is the most significant prognostic factor for long-term survival.
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Affiliation(s)
- Nail Aydin
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
| | - Armando Sardi
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
| | - Vladimir Milovanov
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
| | - Carol Nieroda
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
| | - Michelle Sittig
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
| | - Maria F. Nunez
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
| | - William Jimenez
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
| | - Vadim Gushchin
- Department of Surgical Oncology, Institute for Cancer Care at Mercy Medical Center, Baltimore, Maryland
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Judge S, Thomas P, Govindarajan V, Sharma P, Loggie B. Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment. Ann Surg Oncol 2015; 23:1496-500. [DOI: 10.1245/s10434-015-4965-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Indexed: 01/16/2023]
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Ying C, Maeda M, Nishimura Y, Kumagai-Takei N, Hayashi H, Matsuzaki H, Lee S, Yoshitome K, Yamamoto S, Hatayama T, Otsuki T. Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos. Toxicology 2015; 338:86-94. [PMID: 26505785 DOI: 10.1016/j.tox.2015.10.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 10/08/2015] [Accepted: 10/13/2015] [Indexed: 01/02/2023]
Abstract
Asbestos exposure causes lung fibrosis and various malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos on immune cells have not been thoroughly investigated, although our previous reports showed that asbestos exposure reduced anti-tumor immunity. The effects of continuous exposure of regulatory T cells (Treg) to asbestos were examined using the HTLV-1 immortalized human T cell line MT-2, which possesses a suppressive function and expresses the Treg marker protein, Foxp3. Sublines were generated by the continuous exposure to low doses of asbestos fibers for more than one year. The sublines exposed to asbestos showed enhanced suppressive Treg function via cell-cell contact, and increased production of soluble factors such as IL-10 and transforming growth factor (TGF)-β1. These results also indicated that asbestos exposure induced the reduction of anti-tumor immunity, and efforts to develop substances to reverse this reduction may be helpful in preventing the occurrence of asbestos-induced tumors.
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Affiliation(s)
- Chen Ying
- Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China; Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Megumi Maeda
- Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, Okayama, Japan; Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Yasumitsu Nishimura
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Naoko Kumagai-Takei
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Hiroaki Hayashi
- Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China; Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan
| | - Hidenori Matsuzaki
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Suni Lee
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Kei Yoshitome
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Shoko Yamamoto
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Tamayo Hatayama
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Takemi Otsuki
- Department of Hygiene, 4: Department of Dermatology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
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38
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Abstract
Diffuse malignant peritoneal mesotheliomas in children are uncommon, aggressive tumors with a grave prognosis. We herein report the clinical, radiologic, and pathologic findings of a 16-year-old male. The adolescent presented with a history of abdominal pain, nausea and daily, nonbilious, nonbloody emesis for 3 weeks. Radiographic imaging suggested small bowel obstruction. The diagnostic work-up and differential diagnoses are discussed. Histologically, the tumor was composed of epithelioid cells with a papillary and glandular architectural pattern. A few glands appeared to produce mucinous material. Histochemistry revealed PAS diastase resistant mucin, an inconspicuous finding in diffuse malignant peritoneal mesothelioma. An extensive immunohistochemistry panel (calretinin, WT-1, D2-40, CK 7, CAM 5.2, CK 5/6, CEA, B72.3, CK 20, CD10, CD30, CD15, CD117, PLAP, S100, TFE3, and EMA) confirmed the diagnosis. Of special interest, BAP1 staining was cytoplasmic and consistent with 3p deletion detected by conventional cytogenetics. The ultrastructural analysis demonstrated long microvilli, desmosomes, and intercellular junctions which further supported the diagnosis.
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Ito T, Hamasaki M, Matsumoto S, Hiroshima K, Tsujimura T, Kawai T, Shimao Y, Marutsuka K, Moriguchi S, Maruyama R, Miyamoto S, Nabeshima K. p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer. Am J Clin Pathol 2015; 143:830-8. [PMID: 25972325 DOI: 10.1309/ajcpoatj9l4gcgda] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
OBJECTIVES It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC. METHODS p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion. RESULTS According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%. CONCLUSIONS Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected.
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Affiliation(s)
- Tomohiro Ito
- Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan
- Department of Obstetrics and Gynecology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan
| | - Makoto Hamasaki
- Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan
| | - Shinji Matsumoto
- Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan
| | - Kenzo Hiroshima
- Department of Pathology, Tokyo Women’s Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Tohru Tsujimura
- Department of Pathology, Hyogo College of Medicine, Hyogo, Japan
| | - Toshiaki Kawai
- Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan
| | - Yoshiya Shimao
- Department of Pathology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
| | - Kousuke Marutsuka
- Department of Pathology, Miyazaki University School of Medicine, Miyazaki, Japan
| | - Sayaka Moriguchi
- Department of Pathology, Miyazaki University School of Medicine, Miyazaki, Japan
| | - Riruke Maruyama
- Laboratory of Surgical Pathology, Shimane University School of Medicine, Izumo, Japan
| | - Shingo Miyamoto
- Department of Obstetrics and Gynecology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan
| | - Kazuki Nabeshima
- Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan
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Hemodynamic Monitoring During Heated Intraoperative Intraperitoneal Chemotherapy Using the FloTrac/Vigileo System. Int Surg 2015; 100:1033-9. [PMID: 25590363 DOI: 10.9738/intsurg-d-14-00138.1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cytoreductive surgery with HIPEC has provided a chance for long-term survival in selected patients. However, perioperative management remains a challenge for the anesthesiology team. The aim of this study was to evaluate the changes in hemodynamic parameters during hyperthermic intraperitoneal chemotherapy (HIPEC) using the FloTrac/Vigileo system. Forty-one consecutive patients undergoing cytoreductive surgery and HIPEC were enrolled. Heart rate (HR), esophageal temperature, and cardiac output (CO) steadily increased until the end of HIPEC. In the first half of HIPEC, systolic blood pressure (SBP) and central venous pressure (CVP) increased whereas systemic vascular resistance (SVR) decreased; SVR stabilized in the second half. Diastolic blood pressure (DBP), mean arterial pressure (MAP), and stroke volume (SV) showed no significant variation. Male gender was related to increased CVP, CO, and SV, and decreased SVR; age >55 years was related to increased SBP, and peritoneal cancer index (PCI) was correlated with HR, DBP, and SV. PCI >14 was associated with increased HR and decreased DBP and MAP. American Society of Anesthesiologists score >1 was related to decreased CO and SV. Patients undergoing HIPEC develop a hyperdynamic circulatory state because of the increased temperature, characterized by a steady decrease in SVR and continuous increase in HR and CO. FloTrac/Vigileo system may provide an easy-to-handle, noninvasive monitoring tool.
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Raza A, Huang WC, Takabe K. Advances in the management of peritoneal mesothelioma. World J Gastroenterol 2014; 20:11700-11712. [PMID: 25206274 PMCID: PMC4155360 DOI: 10.3748/wjg.v20.i33.11700] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Revised: 03/21/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023] Open
Abstract
Malignant peritoneal mesothelioma (PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Accordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1 (SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease.
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42
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Helm JH, Miura JT, Glenn JA, Marcus RK, Larrieux G, Jayakrishnan TT, Donahue AE, Gamblin TC, Turaga KK, Johnston FM. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis. Ann Surg Oncol 2014; 22:1686-93. [PMID: 25124472 DOI: 10.1245/s10434-014-3978-x] [Citation(s) in RCA: 166] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate and synthesize the recent published literature. METHODS The review was conducted according to the recommendation of the Meta-Analysis of Observational Studies in Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE method was used to combine mortality rates, and imputation techniques were used to calculate standard errors. Meta-regression techniques were used to synthesize data. Publication bias was assessed using funnel plots. RESULTS Of 6,528 citations collected, 20 articles reporting on 1,047 patients were included in the analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54-67) female. The median peritoneal carcinomatosis index score was 19 (16-23). Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients. Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and 42 %, respectively. Patients receiving early postoperative intraperitoneal chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year survival. CONCLUSIONS While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit.
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Affiliation(s)
- Joseph H Helm
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
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43
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Miura JT, Johnston FM, Gamblin TC, Turaga KK. Current Trends in the Management of Malignant Peritoneal Mesothelioma. Ann Surg Oncol 2014; 21:3947-53. [DOI: 10.1245/s10434-014-3803-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Indexed: 02/01/2023]
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44
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Mery É, Hommell-Fontaine J, Capovilla M, Chevallier A, Bibeau F, Croce S, Dartigues P, Kaci R, Lang-Averous G, Laverriere MH, Leroux-Broussier A, Poizat F, Robin N, Valmary-Degano S, Verriele-Beurrier V, Villeneuve L, Isaac S. Mésothéliome malin péritonéal : mise au point et données actuelles. Ann Pathol 2014; 34:26-33. [DOI: 10.1016/j.annpat.2014.01.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Accepted: 01/10/2014] [Indexed: 01/29/2023]
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Mikami K, Tabata C, Tabata R, Nogi Y, Terada T, Honda M, Kamiya H, Nishizaki T, Nakano T. Clinical significance of serum angiopoietin-1 in malignant peritoneal mesothelioma. Cancer Invest 2013; 31:511-5. [PMID: 24010773 DOI: 10.3109/07357907.2013.830734] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
We have previously reported that angiopoietin-1 was correlated with pulmonary fibrosis. Here, we investigated the serum levels of angiopoietin-1 in patients with malignant peritoneal mesothelioma, which originate from mesenchymal cells similar to lung fibroblasts. We showed that patients with peritoneal mesothelioma had significantly higher serum levels of angiopoietin-1 in comparison with a population with a history of asbestos exposure without peritoneal mesothelioma, and the Kaplan-Meier method revealed a significant correlation between serum angiopoietin-1 levels and survival. This is the first report about the relationship between angiopoietin-1 and peritoneal mesothelioma.
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Affiliation(s)
- Koji Mikami
- Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine,1
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Abstract
BACKGROUND Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, early diagnosis of DMPM is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. DMPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells, similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM. STUDY The serum concentrations of HMGB1 were measured in 13 DMPM patients and 45 individuals with benign asbestos-related diseases. RESULT We demonstrated that the patients with DMPM had significantly higher serum levels of HMGB1 compared with the population who had been exposed to asbestos but did not develop DMPM. CONCLUSION Our data suggest that serum HMGB1 concentration is a useful serum marker for DMPM.
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Carbone A, Pennati M, Parrino B, Lopergolo A, Barraja P, Montalbano A, Spanò V, Sbarra S, Doldi V, De Cesare M, Cirrincione G, Diana P, Zaffaroni N. Novel 1H-pyrrolo[2,3-b]pyridine derivative nortopsentin analogues: synthesis and antitumor activity in peritoneal mesothelioma experimental models. J Med Chem 2013; 56:7060-72. [PMID: 23919303 DOI: 10.1021/jm400842x] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
In this study, we describe the synthesis of new nortopsentin analogues, 1H-pyrrolo[2,3-b]pyridine derivatives and their biological effects in experimental models of diffuse malignant peritoneal mesothelioma (DMPM), a rare and rapidly fatal disease, poorly responsive to conventional therapies. The three most active compounds, 1f (3-[2-(5-fluoro-1-methyl-1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[2,3-b]pyridine), 3f (3-[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1-methyl-1H-pyrrolo[2,3-b]pyridine), and 1l (3-[2-(5-fluoro-1-methyl-1H-indol-3-yl)-1,3-thiazol-4-yl]-1-methyl-1H-pyrrolo[2,3-b] pyridine), which were shown to act as cyclin-dependent kinase 1 inhibitors, consistently reduced DMPM cell proliferation and induced a caspase-dependent apoptotic response, with a concomitant reduction of the expression of the active Thr(34)-phosphorylated form of the antiapoptotic protein survivin. Moreover, the combined treatment of DMPM cells with 3f derivative and paclitaxel produced a synergistic cytotoxic effect, which was paralleled by an enhanced apoptotic response. In the mouse model, i.p. administration of 1f, 3f, and 1l derivatives was effective, resulting in a significant tumor volume inhibition of DMPM xenografts (range, 58-75%) at well-tolerated doses, and two complete responses were observed in each treatment group.
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Affiliation(s)
- Anna Carbone
- Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy
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Baratti D, Kusamura S, Cabras AD, Bertulli R, Hutanu I, Deraco M. Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Cancer 2013; 49:3140-8. [PMID: 23831335 DOI: 10.1016/j.ejca.2013.05.027] [Citation(s) in RCA: 100] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Revised: 03/18/2013] [Accepted: 05/26/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Prognosis of diffuse malignant peritoneal mesothelioma (DMPM) has been recently improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). As with other peritoneal surface malignancies, the survival benefit is maximal when a complete surgical cytoreduction is achieved, but additional factors predicting long-term outcome are still poorly understood. We sought to investigate outcome and prognostic factors in patients with DMPM treated by complete cytoreduction and HIPEC. METHODS From a prospective database, we selected 108 patients with DMPM undergoing complete cytoreduction (residual tumour nodules ≤2.5 mm) and closed-abdomen HIPEC with cisplatin and doxorubicin or mitomycin-C. Twenty-seven patient-, tumour- and treatment-related variables were assessed by multivariate analysis with respect to overall (OS) and progression-free (PFS) survival. A panel of immunohistochemical markers was tested. RESULTS Operative mortality was 1.9% and major morbidity 38.9%. Median follow-up was 48.8 months (95% confidence interval (CI) 37.1-60.6). Median OS and PFS were 63.2 months (95%CI 29.6-96.7) and 25.1 months (95%CI 5.1-45.1). The survival curve reached a plateau after 7 years, representing 19 actual survivors of 39 patients (43.6%) with potential follow-up ≥7 years. Cytokeratin 5/6, calretinin, Wilms tumour-1 (WT-1), podoplanin and epithelial growth factor receptor (EGFR) were mostly positive. At multivariate analysis, epithelial histological subtype, negative lymph-nodes, ≤10% Ki67-positive cells correlated with both increased OS and PFS. Positive podoplanin correlated to increased PFS. CONCLUSIONS After complete cytoreduction and HIPEC, prognosis of DMPM is primarily dependent on pathologic and biologic features. Patients with DMPM surviving ≥7 years appeared to be cured. Cure rate was 43.6%. Proliferative index and podoplanin may be used for prognostic stratification.
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Affiliation(s)
- Dario Baratti
- Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian, 1 20133 Milan, Italy
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Abstract
BACKGROUND Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, diagnosing DMPM early is very important. Reactive oxygen species play an important role in asbestos toxicity, which is associated with the pathogenesis of DMPM growth. Thioredoxin-1 (TRX) is a small redox-active protein that demonstrates antioxidative activity associated with tumor growth. Here, we investigated the serum levels of TRX in patients with DMPM and compared them with those of a population that had been exposed to asbestos but did not have DMPM. STUDY The serum concentrations of TRX were measured in 15 DMPM patients and 34 individuals with benign asbestos-related diseases. RESULTS We demonstrated that the patients with DMPM had significantly higher serum levels of TRX than the population that had been exposed to asbestos but did not have DMPM. CONCLUSIONS Our data suggest that serum TRX concentration is a useful serum marker for DMPM.
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Suchy SL, Landreneau RJ, Schuchert MJ, Wang D, Ervin PR, Brower SL. Adaptation of a chemosensitivity assay to accurately assess pemetrexed in ex vivo cultures of lung cancer. Cancer Biol Ther 2012; 14:39-44. [PMID: 23114649 DOI: 10.4161/cbt.22622] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
PURPOSE Pemetrexed is the only FDA approved treatment for mesothelioma and is a second line agent for treatment of non-small cell lung carcinoma (NSCLC). Pemetrexed is inhibited by folate and its analogs, which are components of many culture media, making it challenging to study pemetrexed in vitro. In order to accurately evaluate pemetrexed's effects in vitro, the protocol for a standard chemosensitivity assay, the ChemoFx drug response marker, had to be modified. EXPERIMENTAL DESIGN Novel rinse and media change steps were assessed and then added to the assay protocol in order to observe pemetrexed activity. The intraday and interday stability of pemetrexed were also established under the adapted protocol. Then, the modified protocol was used to examine pemetrexed in 65 ex vivo lung cancer specimens. RESULTS Substituting 5% RPMI + EGF for BEGM allowed pemetrexed to exert its anticancer activity in the ChemoFx DRM. ChemoFx classified 6.2% of the lung specimens as responsive, 9.2% as intermediate responsive and 84.6% as non-responsive to pemetrexed. CONCLUSIONS Adapting the ChemoFx protocol allowed for the accurate evaluation of pemetrexed anticancer activity in ex vivo lung specimens. ChemoFx evaluation may provide an indication of a patient's clinical response to the drug prior to pemetrexed treatment. Having this information when treatment options are being considered could avoid wasted time, unnecessary costs and needless side effects that are the result of an inappropriate chemotherapy regimen.
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