Lee JM, Pou K, Sadow PM, Chen H, Hu B, Hewison M, Adams JS, Sugarbaker DJ, Fisher ND.

Division of Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA. jaymoonlee@mednet.ucla.edu

Abstract

Objective: To report a case of coincident hypercalcemia and Cushing syndrome arising from mesothelioma.

Methods: We describe the clinical, laboratory, imaging, and pathologic findings of a patient with malignant pleural mesothelioma and elucidate the underlying biologic mechanisms resulting in concurrent overexpression of steroid and polypeptide hormones.

Results: A 62-year-old woman presented with chest discomfort and cough. Radiologic imaging revealed a diffuse pleural-based mass encasing the right lung. There was no invasion into the chest wall, diaphragm, or mediastinum, and there was no distant disease. Laboratory analyses documented hypercalcemia and Cushing syndrome, which were due to ectopic overproduction of 1,25-dihydroxyvitamin D (1,25[OH]₂D) and corticotropin. Surgical resection resulted in normocalcemia with normalization of serum 1,25(OH)₂D and reduction in hypercortisolemia. The extrapleural pneumonectomy specimen revealed overexpression of the 1,25(OH)₂D synthetic enzyme 25-hydroxyvitamin-D-1alpha-hydroxylase (1alpha-hydroxylase) and underexpression of the 1,25(OH)₂D catabolic enzyme 24-hydroxylase. Immunohistochemistry and electron microscopy demonstrated corticotropin and secretory granules in the tumor tissue.

Conclusion: These findings support the evidence for a paracrine role of vitamin D in the resistance of the human host to antigen.

Glossary

resection

surgery to remove part or all of an organ or other structure.

imaging

any method used to produce a picture of internal body structures. Some imaging methods used to detect cancer are x-rays (including mammograms and CT scans), magnetic resonance imaging (MRI), scintigraphy, and ultrasound.

antigen

(an-tuh-jen) a substance that causes the body's immune system to react. This reaction often involves production of antibodies. For example, the immune system's response to antigens that are part of bacteria and viruses helps people resist infections. Cancer cells have certain antigens that can be found by laboratory tests. They are important in cancer diagnosis and in watching response to treatment. Other cancer cell antigens play a role in immune reactions that may help the body's resistance against cancer.

tissue

a collection of cells, united to perform a particular function.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Javedan K, Stevens CW, Forster K.

Radiation Oncology,1 H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. khosrow.javedan@moffitt.org

Abstract

The present work investigated the potential of compensator-based intensity-modulated radiation therapy (CB-IMRT) as an alternative to multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) to treat malignant pleural mesothelioma (MPM) post extrapleural pneumonectomy. Treatment plans for 4 right-sided and 1 left-sided MPM post-surgery cases were generated using a commercial treatment planning system, XIO/CMS (Computerized Medical Systems, St. Louis, MO). We used a 7-gantry-angle arrangement with 6 MV beams to generate these plans. The maximum required field size was 30 x 40 cm. We evaluated IMRT plans with brass compensators (.Decimal, Sanford, FL) by examining isodose distributions, dose-volume histograms, metrics to quantify conformal plan quality, and homogeneity. Quality assurance was performed for one of the compensator plans. Conformal dose distributions were achieved with CB-IMRT for all 5 cases, the average planning target volume (PTV) coverage being 95.1% of the PTV volume receiving the full prescription dose. The average lung V20 (volume of lung receiving 20 Gy) was 1.8%, the mean lung dose was 6.7 Gy, and the average contralateral kidney V15 was 0.6%. The average liver dose V30 was 34.0% for the right-sided cases and 10% for the left-sided case. The average monitor units (MUs) per fraction were 980 MUs for the 45-Gy prescriptions (mean: 50 Gy) and 1083 MUs for the 50-Gy prescriptions (mean: 54 Gy). Post surgery, CB-IMRT for MPM is a feasible IMRT technique for treatment with a single isocenter. Compensator plans achieved dose objectives and were safely delivered on a Siemens Oncor machine (Siemens Medical Solutions, Malvern, PA). These plans showed acceptably conformal dose distributions as confirmed by multiple measurement techniques. Not all linear accelerators can deliver large-field MLC-based IMRT, but most can deliver a maximum conformal field of 40 x 40 cm. It is possible and reasonable to deliver IMRT with compensators for fields this size with most conventional linear accelerators.

Glossary

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

radiation therapy

treatment with radiation to destroy cancer cells. This type of treatment may be used to reduce the size of a cancer before surgery, to destroy any remaining cancer cells after surgery, or, in some cases, as the main treatment.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

IMRT

(intensity-modulated radiation therapy) an advanced mode of high-precision radiotherapy that utilizes computer-controlled x-ray accelerators to deliver thin beams of radiation of different strengths (beams of modulating intensity) directly to the tumor from many angles. Higher and more effective radiation doses can safely be delivered to tumors with fewer side effects as compared to conventional radiotherapy techniques. Even when doses are not increased, IMRT can potentially reduce treatment toxicity.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Arrossi AV, Lin E, Rice D, Moran CA.

Department of Anatomic Pathology, University of Texas M.D. Anderson Cancer Center, Houston, USA.

Abstract

We studied 56 cases of malignant pleural mesothelioma (MPM) treated with extrapleural pneumonectomy (EPP). The slides from the EPP specimens were reviewed, and tumors were classified with the guidance of the World Health Organization classification of pleural tumors. Agreement between the histologic type from the EPP review and the diagnostic procedure (DP) reports was evaluated. Histologic and clinical parameters were also correlated with clinical outcome. There was a significant disagreement (P = .0001) between the histologic type in the DP reports and the EPP specimen review. The histologic type from the DP was associated with disease-specific survival (DSS); however, the histologic type from the EPP specimen was not associated with survival. Postoperative treatment was associated with DSS and with recurrence-free survival. Our study confirms that in many cases, final histopathologic typing of MPM is influenced by complete surgical resection and that initial biopsy should be carefully weighed in the treatment stratification.

Glossary

resection

surgery to remove part or all of an organ or other structure.

recurrence

cancer that has come back after treatment. Local recurrence is when the cancer comes back at the same place as the original cancer. Regional recurrence is when the cancer appears in the lymph nodes near the first site. Distant recurrence is when it appears in organs or tissues (such as the lungs, liver, bone marrow, or brain) farther from the original site than the regional lymph nodes. Metastasis means that the disease has recurred at a distant site.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

biopsy

(buy-op-see) the removal of a sample of tissue to see whether cancer cells are present. There are several kinds of biopsies. In some, a very thin needle is used to draw fluid and cells from a lump. In a core biopsy, a larger needle is used to remove more tissue.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Flores RM, Routledge T, Seshan VE, Dycoco J, Zakowski M, Hirth Y, Rusch VW.

Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. floresr@mskcc.org

Abstract

Objectives: The propensity of malignant pleural mesothelioma to metastasize to N1 or N2 nodes and their corresponding prognostic value is unclear. The American Joint Committee on Cancer staging system groups N1 and N2 disease together as stage III. The goal of this study was to define the prognostic value of specific nodal stations.

Methods: Patients with malignant pleural mesothelioma who underwent resection were identified from an institutional database. Nodal stations were defined by the American Joint Committee on Cancer lung cancer node map classification. Survival was analyzed by the Kaplan–Meier method, log-rank test, and Cox proportional hazards analysis.

Results: From 1990 to 2006, 348 patients were identified: 279 men and 69 women with a median age of 67 years (range 26–85 years). Extrapleural pneumonectomy was performed in 223 cases, and pleurectomy/decortication was performed in 125 cases. Survival differences (P < .01) were observed between 2 groups: N0 or N1(+) (median survival = 19 months) and N2(+), N2/N1(+) and internal thoracic(+) (median survival = 10 months). Survival was influenced by the number of involved N2 stations (0, 1, 2, or more: P < .001). Multivariate analysis grouping all N2 and internal thoracic(+) versus N1(+) and N0 demonstrated a hazard ratio for survival of 1.7 (P < .0001) controlling for T3/T4 status (hazard ratio = 1.3, P < .01), non-epithelioid histology (hazard ratio = 1.7, P < .0001), extrapleural pneumonectomy (1.1, P = .4), and male gender (hazard ratio 1.4, P < .01).

Conclusion: This study confirms a preferential pattern of drainage of malignant pleural mesothelioma to N2 rather than N1 lymph nodes, but suggests that N1 only nodal involvement should be classified as lower stage disease. Multiple N2 nodal site involvement could potentially be classified as higher stage disease than single station N2. Our results emphasize the need for larger, confirmatory multicenter studies that could lead to revision of the current staging system.

Glossary

staging

the process of finding out whether cancer has spread and if so, how far. There is more than one system for staging. The TNM system, described below, is one used often. The TNM system for staging gives three key pieces of information: T refers to the size of the Tumor N describes how far the cancer has spread to nearby Nodes M shows whether the cancer has spread (Metastasized) to other organs of the body Letters or numbers after the T, N, and M give more details about each of these factors. To make this information somewhat clearer, the TNM descriptions can be grouped together into a simpler set of stages, labeled with Roman numerals. In general, the lower the number, the less the cancer has spread. A higher number means a more serious cancer.

resection

surgery to remove part or all of an organ or other structure.

lymph nodes

small bean-shaped collections of immune system tissue such as lymphocytes, found along lymphatic vessels. They remove cell waste and fluids from lymph and help fight infections. Also called lymph glands.

lymph

(limf) clear fluid that flows through the lymphatic vessels and contains cells known as lymphocytes. These cells are important in fighting infections and may also have a role in fighting cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Sørensen JB, Ravn J, Loft A, Brenøe J, Berthelsen AK; Nordic Mesothelioma Group.

Aaseboe U, Billing B, Bjørck T, Brodin O, Brunsvig P, Forsløw U, Frank H, Hansen O, Harving H, Hillerdal G, Jakobsen KD, Johansson A, Ladegaard L, Lindh B, Melgaard P, Mygind N, Månsson T, Palshof T, Sundstrøm S, Sørensen P, Vigander T.

Department of Oncology, Finsen Centre/National University Hospital, Copenhagen, Denmark. jens.benn.soerensen@rh.regionh.dk

Abstract

Objectives: Extrapleural pneumonectomy (EPP) in MPM may be confined with both morbidity and mortality and careful preoperative staging identifying resectable patients is important. Staging is difficult and the accuracy of preoperative CT scan, 18F-FDG PET/CT scan (PET/CT), and mediastinoscopy is unclear. The objectives were to compare these staging techniques to each other and to surgical–pathological findings.

Methods: Patients had epithelial subtype MPM, age ≤70 years, and lung function test allowing pneumonectomy. Preoperative staging after 3–6 courses of induction chemotherapy included conventional CT scan, PET/CT, and mediastinoscopy. Surgical–pathological findings were compared to preoperative findings.

Results: Forty-two consecutive patients were without T4 or M on CT scan. PET/CT showed inoperability in 12 patients (29%) due to T4 (7 patients) and M1 (7 patients). Among 30 patients with subsequent mediastinoscopy, including 10 with N2/N3 on PET/CT, N2 were histologically verified
in 6 (20%). Among 24 resected patients, T4 occurred in 2 patients (8%), and N2 in 4 (17%), all being PET/CT negative. PET/CT accuracy of T4 and N2/N3 compared to combined histological results of mediastinoscopy and EPP showed sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios of 78% and 50%, 100% and 75%, 100% and 50%, 94% and 75%, not applicable and 5.0, and 0.22 and 0.67, respectively.

Conclusions: Non-curative surgery is avoided in 29% out of 42 MPM patients by preoperative PET/CT and in further 14% by mediastinoscopy. Even though both procedures are valuable, there are false negative findings with both, urging for even more accurate staging procedures.

Keywords: Mesothelioma; Staging; PET/CT scan; Mediastinoscopy; Extrapleural pneumonectomy

Glossary

staging

the process of finding out whether cancer has spread and if so, how far. There is more than one system for staging. The TNM system, described below, is one used often. The TNM system for staging gives three key pieces of information: T refers to the size of the Tumor N describes how far the cancer has spread to nearby Nodes M shows whether the cancer has spread (Metastasized) to other organs of the body Letters or numbers after the T, N, and M give more details about each of these factors. To make this information somewhat clearer, the TNM descriptions can be grouped together into a simpler set of stages, labeled with Roman numerals. In general, the lower the number, the less the cancer has spread. A higher number means a more serious cancer.

scan

a study using either x-rays or radioactive isotopes to produce images of internal body organs.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

morbidity

a measure of the new cases of a disease in a population; the number of people who have a disease.

mortality

a measure of the rate of death from a disease within a given population.

mediastinoscopy

(me-dee-as-tin-OS-ko-pee) examination of the chest cavity using a lighted tube replaced under the chest bone (sternum). This allows the doctor to see the lymph nodes in this area and remove samples to check for cancer.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

CT scan

computed tomography (tom-og-ruh-fee), an imaging test in which many x-rays are taken of a part of the body to produce cross-sectional pictures of internal organs. Except for the injection of a dye (needed in some but not all cases), this is a painless procedure that can be done in an outpatient clinic. It is often referred to as a "CT" or "CAT" scan.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Ramalingam SS, Belani CP.

Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.

Abstract

Malignant pleural mesothelioma clinically manifests after decades of initial exposure to etiologic agents, such as asbestos, and presents with nonspecific symptoms such as dyspnea, pain, or weight loss. In patients with limited, resectable disease, surgical therapy with extrapleural pneumonectomy or pleurectomy is recommended, although, it is unclear which approach is superior. Radiation has a limited role and is used primarily for palliation. The palliative efficacy of traditional chemotherapeutic agents and combination regimens is modest at best. The combination of cisplatin and pemetrexed, a novel multitargeted antifolate agent, is the approved "standard of care" for patients with unresectable malignant pleural mesothelioma. A number of molecularly targeted agents are currently under evaluation for mesothelioma such as the Histone deacetylase (HDAC) inhibitors that have demonstrated promising anticancer activity. Vorinostat, a small molecule inhibitor of HDAC, which targets select members of class I and II HDACs, has shown early evidence of activity and is currently being evaluated in a randomized study for patients who progress with standard therapy for advanced mesothelioma. It is hoped that the HDAC inhibitors and other novel targeted agents will pave the way for improved outcomes for patients with this disease.

Glossary

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Kent M, Rice D, Flores R.

Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Abstract

Opinion statement: The clinical presentation of malignant pleural mesothelioma (MPM) is nonspecific. The process to obtain the correct diagnosis can be challenging and requires a high index of suspicion. Once the diagnosis is made, there is no universally accepted standard of care and treatment decisions are strongly influenced by physician bias. Physicians who see few numbers of patients tend to treat based on symptoms alone by drainage of the pleural effusion and talc pleurodesis, while physicians at several tertiary referral centers tend to take an aggressive multimodality approach incorporating surgical resection, chemotherapy, and radiation. The primary goal of surgery in this setting is the resection of all gross disease. The choice of operation, extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D), depends on disease stage, pulmonary function, philosophy of the treating physician, and type of planned adjuvant therapy.

Glossary

adjuvant therapy

(add-joo-vunt) treatment used in addition to the main treatment. It usually refers to hormonal therapy, chemotherapy, or radiation added after surgery to increase the chances of curing the disease or keeping it in check.

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

resection

surgery to remove part or all of an organ or other structure.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

pleural effusion

an abnormal accumulation of fluid, usually caused by trauma or disease, in the pleural space.

Neragi-Miandoab S, Winer S, Sugarbaker DJ.

New York Medical College, School of Medicine, New York, USA.

Abstract

Extrapleural pneumonectomy (EPP) and pleurectomy are the surgical procedures for the treatment of pleural mesothelioma. However, EPP increases the risk for postoperative atrial fibrillation (AF) in this patient population, which might be partly explained by increase in right heart stress after EPP. We conducted a retrospective chart review of 130 patients who were treated for malignant pleural mesothelioma with either pleurectomy or EPP between 2001 and 2003 in a single institution. Risk factors for AF were evaluated with logistic regression and the postoperative AF events were evaluated. The absence of a history of cardiac arrhythmia was an inclusion criterion. Seventy patients (excluding the 3 patients with a prior history of AF) underwent EPP and 57 patients underwent pleurectomy. The mean ages were 60+/-11 and 63+/-13, and the male to female ratios were 50/20 and 44/13, respectively. Postoperative AF was observed in 45 patients with 36 (51%) of these cases occurring after EPP and 9 (17%) after pleurectomy (p<0.0001). There were no significant differences between the two treatment groups for gender, age, side of affected lung, preoperative heart rate and history of beta-blocker use, coronary heart disease, and chronic obstructive pulmonary disease. There were significant differences between the two groups for cancer histology (p=0.03) with the EPP group having a larger proportion of epithelial-type histology. Through logistic regression, EPP (OR=7.1, 95% CI: 2.9, 17.8) and age over 65 (OR=2.9, 95% CI: 1.2, 6.8) were found to be risk factors for AF. Abnormal cardiac structure and function were identified as important possible confounder, which could not be adequately evaluated due to missing data. Most of these patients had at least one additional expected risk factor for AF. EPP versus pleurectomy and age over 65 are risk factors for postoperative AF. The increased odds of having AF after EPP could be due to right heart stress caused by pneumonectomy. Increased right heart stress might not be sufficient to cause AF alone, but may be an important risk factor that warrants further investigation.

Keywords: Right heart stress; Extrapleural pneumonectomy; Pleurectomy; Atrial fibrillation.

Glossary

risk factor

anything that increases a person's chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposure to sunlight is a risk factor for skin cancer, smoking is a risk factor for lung and other cancers, and a high-fat, low-fiber diet is a risk factor for colorectal cancer. Some risk factors, such as smoking, can be controlled. Others, like a person's age, can't be changed

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Hasegawa S, Tanaka F.

Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan, hasegawa@hyo-med.ac.jp.

Abstract

Malignant pleural mesothelioma (MPM) is associated with a poor prognosis; and to make things worse, its incidence is increasing throughout the world. Surgical management of MPM is comprised of two aspects: diagnosis and resection. Surgical biopsy with thoracoscopy provides a higher yield but a higher rate of tumor cell seeding than blind biopsy. In some surgical cases, extended surgical staging with mediastinoscopy, laparoscopy, and contralateral thoracoscopy is required for the preoperative evaluation for resectablity. There are two types of surgical resection for MPM. Pleurectomy/decortication (P/D) involves removal of as much of the visceral, parietal, and pericardial pleura and the tumor as possible without removing the underlying lung. Because P/D is less radical but less invasive compared to extrapleural pneumonectomy (EPP), it can be tolerated by poor-risk patients. EPP comprises en bloc resection of visceral, parietal, and pericardial pleura and adjacent components such as ipsilateral lung, pericardium, and diaphragm, without opening the pleural cavity. EPP was considred a highly dangerous procedure with a surgical mortality of more than 30% decades ago, but its current operative mortality/morbidity rates are 4%-9% and 60%, respectively. As macroscopic complete resection is the primary goal of surgery for MPM because of its diffuse intrapleural growth, surgical resection alone is associated with poor survival. In this context, combination therapy with surgery plus chemotherapy and/or radiotherapy is currently considered the standard treatment for patients with respectable MPM. A national survey of EPP was conducted recently in Japan, and a few multicenter clinical trials will start soon

Keywords: Malignant pleural mesothelioma – Pleurectomy – Extrapleural pneumonectomy – Chemotherapy – Multimodality treatment

Glossary

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

surgical biopsy

see biopsy

staging

the process of finding out whether cancer has spread and if so, how far. There is more than one system for staging. The TNM system, described below, is one used often. The TNM system for staging gives three key pieces of information: T refers to the size of the Tumor N describes how far the cancer has spread to nearby Nodes M shows whether the cancer has spread (Metastasized) to other organs of the body Letters or numbers after the T, N, and M give more details about each of these factors. To make this information somewhat clearer, the TNM descriptions can be grouped together into a simpler set of stages, labeled with Roman numerals. In general, the lower the number, the less the cancer has spread. A higher number means a more serious cancer.

resection

surgery to remove part or all of an organ or other structure.

prognosis

(prog-no-sis) a prediction of the course of disease; the outlook for the cure of the patient. For example, women with breast cancer that was detected early and who received prompt treatment have a good prognosis.

pleura

(pler-uh) the membrane around the lungs and lining of the chest cavity. (Pleural mesothelioma.)

morbidity

a measure of the new cases of a disease in a population; the number of people who have a disease.

mortality

a measure of the rate of death from a disease within a given population.

mediastinoscopy

(me-dee-as-tin-OS-ko-pee) examination of the chest cavity using a lighted tube replaced under the chest bone (sternum). This allows the doctor to see the lymph nodes in this area and remove samples to check for cancer.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

biopsy

(buy-op-see) the removal of a sample of tissue to see whether cancer cells are present. There are several kinds of biopsies. In some, a very thin needle is used to draw fluid and cells from a lump. In a core biopsy, a larger needle is used to remove more tissue.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Neragi-Miandoab S, Richards WG, Sugarbaker DJ.

Department of Surgery, Cardiothoracic Surgery, Boston University Medical Center, School of Medicine, One Boston Medical Center Place, Boston MA 02118, United States.

Abstract

Aim: The survival of patients with malignant pleural mesothelioma (MPM) who do not seek treatment ranges from 4 to 12 months. To date, the optimal procedure for resection of malignant pleural mesothelioma is controversial, extrapleural pneumonectomy has been most consistently associated with long-term survival and has provided the most radical cytoreduction; but, unfortunately, not all patients qualify for this invasive surgical approach.

Methods: Between 1992 and 2000, 64 patients underwent pleurectomy as a palliative treatment for MPM. This retrospective study evaluates the operative outcome and the impact of some prognostic factors on patients’ survival. Preoperative evaluation included chest X-ray, CT and/or MRI. Diagnosis was made by pleural biopsy via needle, open, or VATS biopsy. The Kaplan-Meier curve and the Log-Rank test were used to analyze the data.

Results: The median age of the study group was 65 (with a range of 29-84 years). Thirty-six patients had epithelial histology, and 28 patients had sarcomatoid or mixed type (e.g., epithelial+spindle, epithelial+sarcomatoid). The 30-day mortality rate was 3.1%. The overall survival rate was 43%, 28%, and 10% at 1, 2, and 3 years, respectively. The overall median survival was 9.4 months (ranging from 1.15 to 52.7 months). The overall median survival with epithelial histology (n=36, 56%) was 21.7 months (with a range of 1.4-52.7 months) versus 5.8 months (with a range of 1.15-18.3 months) for the sarcomatoid or mixed type (n=28, 44%), p=0.0001. The morbidity included atrial fibrillation (n=5), wound infection (n=2), prolonged intubation (longer than 24h, n=8), reintubation for respiratory failure (n=2), pulmonary emboli (n=1), UTI (n=16), DVT (n=5), MI (n=4), and postoperative bleeding (n=7). Univariant analysis demonstrated that the only prognostic factors influencing survival in our series was the histologic type. Age, gender, and the affected side of the lung did not affect the median survival.

Conclusion: Our results show that pleurectomy can be performed as a means of palliation for advanced-stage disease with a low mortality rate and may, in fact, improve survival in patients with epithelial subtype as compared with historical controls in the literature with no surgical intervention.

Glossary

survival rate

the percentage of survivors with no trace of disease within a certain period of time after diagnosis or treatment. For cancer, a 5-year survival rate is often given. This does not mean that people can't live more than five years, or that those who live for 5 years are necessarily permanently cured.

resection

surgery to remove part or all of an organ or other structure.

morbidity

a measure of the new cases of a disease in a population; the number of people who have a disease.

mortality

a measure of the rate of death from a disease within a given population.

MRI

Stands for magnetic resonance imaging. A method of taking pictures of the inside of the body. Instead of using x-rays, MRI uses a powerful magnet and transmits radio waves through the body; the images appear on a computer screen as well as on film. Like x-rays, the procedure is physically painless, but some people find it psychologically uncomfortable to be in the small core of the MRI machine.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

biopsy

(buy-op-see) the removal of a sample of tissue to see whether cancer cells are present. There are several kinds of biopsies. In some, a very thin needle is used to draw fluid and cells from a lump. In a core biopsy, a larger needle is used to remove more tissue.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.