Malignant Peritoneal Mesothelioma: a Case Report

In this paper we report a case of malignant peritoneal mesothelioma, a rare abdominal tumour. A 72-year-old male with a medical history of heart disease presented to our Clinic because of pain in the right half of the abdomen. Diagnostic procedures, including clinical and laboratory examination, X-ray, ultrasonography and computed tomography, revealed a tumour in the right lower quadrant of the abdomen. The approximate size of the tumour size at initial detection was 7 cm. During the pre-operative procedure an evident growth of the tumour was noticed, indicating exploratory laparotomy. Intra-operative findings revealed a large tumour of the anterolateral abdominal wall, involving the greater omentum. Tumour resection was performed, as well as resection of the portion of the anterolateral abdominal wall and omentectomy. Postoperative immunohistochemical analysis revealed malignant peritoneal mesothelioma.     

Prognostic Analysis of Clinicopathologic Factors in 49 Patients With Diffuse Malignant Peritoneal Mesothelioma Treated With Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

Background Diffuse malignant peritoneal mesothelioma (DMPM) is a subset of peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic analysis in a cohort of DMPM patients treated homogeneously by cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP). Methods Forty-nine DMPM patients who underwent 52 consecutive procedures were enrolled onto the study. Cytoreductive surgery was performed according to the peritonectomy technique, and the IPHP was performed with cisplatin plus doxorubicin or cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic variables (previous surgical score, age, sex, performance status, previous systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction, IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix metalloproteinase 9]) with overall and progression-free survival. Results The mean age was 52 years (range, 22–74 years). The mean follow-up was 20.3 months (range, 1–89 months). Regarding the biological markers, the rates of immunoreactivity of epidermal growth factor receptor, p16, matrix metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%, respectively. The strongest factors influencing overall survival were completeness of cytoreduction and MC, whereas those for progression-free survival were performance status and MC. No biological markers were shown to be of prognostic value. Conclusions Completeness of cytoreduction, performance status, and MC seem to be the best determinants of outcome. These data warrant confirmation by a further prospective formal trial. No biological markers presented a significant correlation with the outcome. The overexpression of epidermal growth factor receptor, matrix metalloproteinase 2, and matrix metalloproteinase 9 and absent or reduced expression of p16 might be related to the underlining tumor kinetics of DMPM and warrant further investigation with other methods.     

Laparoscopy and Primary Diffuse Malignant Peritoneal Mesothelioma: a Diagnostic Challenge

Primary diffuse malignant peritoneal mesothelioma is a rare malignancy with an estimated incidence of 200 to 400 new cases annually in the USA. We describe a case of diffuse malignant peritoneal mesothelioma arising in a 65-year old man who presented ascites of unknown origin. The importance of laparoscopy with subsequent histology of biopsy specimens in the diagnosis of this disease is emphasized. Because of his poor general condition, the patient had no further treatment. Update of treatment is briefly described with particular attention to multimodality approach.     

Lymph Node Metastases in Diffuse Malignant Peritoneal Mesothelioma

Background  

Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The significance of lymph node involvement in this disease is still poorly understood.     

Current Trends in the Management of Malignant Peritoneal Mesothelioma

Background

Historically, malignant peritoneal mesothelioma (MPM) has been considered an aggressive and lethal neoplasm. However, contemporary series have demonstrated improved outcomes following a combination of cytoreductive surgery and intraperitoneal chemotherapy. We sought to assess the trends in management and survival of patients with MPM in the United States.

Methods

The Surveillance, Epidemiology, and End Results database was used to identify all patients diagnosed with malignant peritoneal mesothelioma from 1973 to 2010. Overall survival (OS) was studied with Kaplan–Meier curves and Cox regression analyses.

Results

We identified 1,591 patients with MPM. Median age at diagnosis was 64 years (IQR 53–74 years) with the majority of patients presenting with metastatic disease (n = 962, 60.5 %). A total of 980 patients (61.6 %) did not receive surgical therapy. Receipt of radical cytoreduction for patients with metastatic MPM demonstrated a significant improvement in OS compared with patients not receiving surgery (20 vs. 4 months, p < 0.01). A temporal increase was observed in OS for patients receiving surgery (1991–1995: 15 vs. 2006–2010: 38 months, p = 0.1). In multivariate models, limited (HR 0.55; 95 % CI 0.48–0.63; p < 0.01) and radical (HR 0.66; 95 % CI 0.54–0.80; p < 0.01) surgery were independently associated with improved survival.

Conclusions

In the current era, approximately three of every five patients do not receive surgery when diagnosed with MPM, although a significant survival benefit is noted in select patients. The opportunity to improve patient survival with surgical therapy is lost in a significant number of MPM patients.     

Diffuse Malignant Peritoneal Mesothelioma: Failure Analysis Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The issue of treatment failure has never been extensively addressed. The present study assessed the failure pattern, management, and outcome of progressive DMPM following comprehensive treatment. Clinical data on 70 patients with DMPM undergoing cytoreduction and HIPEC were prospectively collected; after a median follow-up of 43 months, disease progression occurred in 38 patients. Progressive disease distribution in 13 abdominopelvic regions was analyzed. In 28 patients undergoing adequate cytoreduction (residual tumor ≤2.5 mm), clinicopathological factors correlating to disease progression in each region were investigated. Median time to progression was 9 months [95% confidence interval (CI) 1.6–35.9]. Median survival from progression was 8 months (95% CI 4–16.2). The failure pattern was categorized as peritoneal progression (n = 31), liver metastases (n = 1), abdominal lymph-node involvement (n = 2), pleural seeding (n = 4). Small bowel was the single site most commonly involved (n = 27). Residual tumor ≤2.5 mm (versus no visible) was the only independent risk factor for disease progression in epigastric region (P = 0.047), upper ileum (P = 0.029), upper jejunum (P = 0.034), and lower jejunum (P = 0.002). Progressive disease was treated with second HIPEC in 3 patients, debulking in 4, systemic chemotherapy in 16, and supportive care in 15. At multivariate analysis, time to progression <9 months (P = 0.009), poor performance status (P = 0.005), and supportive care (P = 0.003) correlated to reduced survival from progression. We conclude that minimal residual disease, compared with macroscopically complete cytoreduction, correlated to failure in critical anatomical areas, suggesting the need for maximal cytoreductive surgical efforts. In selected patients, aggressive management of progressive disease seems worthwhile.     

Parasternal Lymph Node Metastasis of Malignant Peritoneal Mesothelioma: Report of a Case

We report a case of malignant peritoneal mesothelioma with parasternal lymph node metastasis. The patient was a 34-year-old man who presented with a history of several years of abdominal pain and ascites of unknown origin. Exploratory laparoscopic biopsies yielded histological findings of malignancy, but a final diagnosis was not able to be made. A chest computed tomographic scan done the following year showed a parasternal nodule, and thoracoscopically obtained biopsied material was positive for calretinin. These findings led to a pathological diagnosis of metastasis to the parasternal lymph node from peritoneal mesothelioma.     

我国165例腹膜恶性间皮瘤临床特点

目的：总结我国腹膜恶性间皮瘤的临床表现及诊治方法。方法：以腹膜恶性间皮瘤为检索词,分别对中国期刊网全文数据库、维普资讯网中文科技期刊数据库在2000—2010年期间发表的中文临床报道进行检索。结果：共检出腹膜恶性间皮瘤165例,男性多于女性。临床症状以腹痛、腹胀为最常见,出现率约为77.8%及63.9%。腹水是最常见的体征,出现率约为96%。剖腹及腹腔镜下探查是确诊的最常见手段。腹膜恶性间皮瘤预后较差,综合治疗后中位生存期约1.5年。结论：腹膜恶性间皮瘤是临床罕见病,误诊率高,应充分认识其特点,提高早期诊治腹膜恶性间皮瘤的水平。积极的综合治疗可以延长病人的生存期。     

Summary of Prognostic Factors and Patient Selection for Extrapleural Pneumonectomy in the Treatment of Malignant Pleural Mesothelioma

Background  

Extrapleural pneumonectomy (EPP) has been shown to improve long-term survival outcomes in selected patients with malignant pleural mesothelioma (MPM). The present study aimed to evaluate potential prognostic factors on overall survival for patients who underwent EPP for MPM and to examine the patient selection process in major referral centers that perform EPP.     

Primary Malignant Peritoneal Mesothelioma in an Incarcerated Groin Hernia: Report of a Case

Malignant peritoneal mesothelioma arising from the inguinal hernia sac is rare. We report the case of a 71-year-old man examined in our emergency department for a bilateral inguinoscrotal hernia, which was recurrent in the right groin, and primary and incarcerated in the left groin. An emergency exploratory operation revealed a firm mass, 10cm in diameter, in the left inguinal hernia sac. The remaining peritoneal surface appeared macroscopically normal. Therefore, we resected the mass and performed a Rutkow hernioplasty. The patient was discharged after a short, uneventful recovery, and was referred to the oncology department for adjuvant therapy. He is now well and asymptomatic with no evidence of ascites, 26 months after his operation. A mesothelioma of the hernial sac peritoneum was the final histological diagnosis.     

Cytoreductive Surgery with Intraperitoneal Hyperthermic Chemotherapy for Malignant Peritoneal Mesothelioma: Mitomycin Versus Cisplatin

Background  

Malignant peritoneal mesothelioma (MPM) is a rare, rapidly fatal disease. Because traditional treatments offer little benefit, there has been increasing interest in cytoreductive surgery (CS) with intraperitoneal hyperthermic chemotherapy (IPHC). The most efficacious chemotherapy regimen is not established. Herein we report clinical outcomes of MPM patients treated with CS and IPHC and contrast results using two chemoperfusates: mitomycin and cisplatin.     

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma

Purpose

Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity.

Methods

The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM.

Results

The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly. Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is < 1 year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1 year.

Conclusion

The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3 K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

     

Quantitative X-ray Computed Tomography Peritoneography in Malignant Peritoneal Mesothelioma Patients Receiving Intraperitoneal Chemotherapy

Background

Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients.

Methods

Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR.

Results

Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167).

Discussion

Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment’s surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

     

Oncolytic Vaccinia Virus as an Adjuvant Treatment to Cytoreductive Surgery for Malignant Peritoneal Mesothelioma

Background

Malignant peritoneal mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. This experimental study aimed to examine the potential of modified vaccinia virus (VV) to treat MPM when administered alone or as an adjuvant treatment to surgery.

Methods

Two aggressive murine mesothelioma cell lines (AC29, AB12), were used. Cell viability and viral cytopathic effects were assessed using MTS and crystal violet assays. Immunocompetent mice were injected intraperitoneally with MPM cells and treated with intraperitoneal VV. Tumor-bearing mice also underwent cytoreductive surgery (CRS) followed by VV (or control) therapy.

Results

The cytotoxic effects of VV on MPM cell lines was significantly increased compared with the control non-cancer cell line. In both orthotopic models, VV induced tumor regression, prolonging median and long-term survival. VV treatment after incomplete CRS was not superior to VV alone; however, when mice with microscopic disease were treated with VV, further prolongation of median and long-term survivals was observed.

Conclusions

VV selectively kills MPM cells in vitro and leads to improved survival and cures in immunocompetent murine models. Higher efficacy of the virus in the microscopic disease context suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of VV in humans as a novel treatment for MPM.     

Prognostic Factors in Gastric Carcinoma with Peritoneal Dissemination

Objective: The prognosis for gastric carcinoma patients with peritoneal dissemination is very poor. We evaluated the survival benefit of resection and intravenous chemotherapy in these patients.

Material and methods: We reviewed the hospital records of 348 gastric carcinoma patients with peritoneal dissemination seen during the period from 1986 to 2000.

Results: Based on the grade of anaplasia, 76 (21.8%) were differentiated and 272 (78.2%) were undifferentiated. In the univariate analyses, the factors influencing the 5-year survival rate were histologic type, resection, and intravenous chemotherapy. Using Cox’s proportional hazard regression model, two factors were independent, statistically significant prognostic parameters: resection (risk ratio, 1.48; 95% confidence interval, 0.90-2.46; p<0.05) and intravenous chemotherapy (risk ratio, 1.68; 95% confidence interval 1.15-2.47; p < 0.01). The 5-year survival rate was higher for patients who had intravenous chemotherapy (3.6%) than for patients who did not (2.4%), and also higher for patients who underwent resection (4.8%) than for patients who did not (0%; p < 0.001).

Conclusion: The results highlight the improved survivorship of gastric carcinoma patients with peritoneal dissemination who had resection and received intravenous chemotherapy, compared with those who did not. Although curative resection cannot be performed in this group of patients, we recommend performing resection and subsequent intravenous chemotherapy.     

Cystic Peritoneal Mesothelioma: Report of a Case

(Received for publication on Aug. 24, 1998; accepted on July 13, 1999)     

Resection of Peritoneal Implantation of Hepatocellular Carcinoma after Hepatic Resection: Risk Factors and Prognostic Analysis

Peritoneal implantation from hepatocellular carcinoma (HCC) after hepatic resection is infrequent, and information on risk factors and long-term survival of such patients is lacking. The clinicopathologic features and risk factors of 16 HCC patients after hepatic resection who developed peritoneal implantation from an HCC and the prognosis after surgical resection of these HCC implants were assessed. The clinical features of 16 HCC patients after hepatic resection undergoing resection of peritoneal HCC implants (P-HCC) from 1986 and 2000 were reviewed. The clinical features and outcomes of 195 HCC patients undergoing hepatectomy without recurrence (NR-HCC) were used for comparison. During 1986 and 2000 a total of 749 HCC patients underwent hepatic resection. Of these 749 patients, 465 (62.1%) had HCC recurrence after hepatic resection during the follow-up period (median 26 months). Of the 465 patients, 26 (5.6%) developed peritoneal implants, and 16 of them underwent resection. Multivariate logistic regression analysis revealed that a high -fetoprotein (AFP) level and capsular invasion by the tumor cells may predispose posthepatectomy patients to peritoneal implantation from their HCCs. The overall survival of the P-HCC patients after peritoneal implant resection was similar to that of the NR-HCC patients. An elevated AFP level might be regarded as a significant prognostic factor for poor overall survival (p = 0.0577) after resection of peritoneal implants from HCCs. Peritoneal implantation occurs infrequently in posthepatectomy patients with an HCC. Elevated AFP values and capsule invasion by tumor cells may predispose posthepatectomy patients to peritoneal implantation from HCCs. Surgical resection of peritoneal implants from HCCs may prolong survival in selected patients. Elevated AFP levels may be regarded as a possibly significant prognostic factor for poor overall survival after resection of peritoneal HCC implants.