Fukazawa T, Matsuoka J, Naomoto Y, Maeda Y, Durbin ML, Tanaka N.

Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. FukazawaT@aol.com

Abstract

Gene therapy and virotherapy are one of the approaches used to treat malignant pleural mesothelioma. To improve the efficiency of targeting malignant mesothelioma cells, we designed a novel system using the promoter of the CREBBP/EP300 inhibitory protein 1 (CRI1), a gene specifically expressed in malignant pleural mesothelioma. Four tandem repeats of the CRI1 promoter (CRI1(-138 4x)) caused significantly high promoter activity in malignant pleural mesothelioma cells but little promoter activity in normal mesothelial cells and normal fibroblasts. The recombinant adenoviral vector expressing proapoptotic BH3-interacting death agonist or early region 1A driven by the CRI1(-138 4x) promoter induced cell death in malignant mesothelioma cells but not in normal cells. Moreover, these viruses showed antitumor effects in a mesothelioma xenograft mouse model. Here, we describe a novel strategy to target malignant mesothelioma using the CRI1(-138 4x) promoter system.

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.

gene therapy

a new type of treatment in which defective genes are replaced with normal ones. The new genes are delivered into the cells by viruses or proteins. (Mesothelioma gene therapy treatment options.)

gene

a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.

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.

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.

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.

Kusamura S, O’Dwyer ST, Baratti D, Younan R, Deraco M.

Department of Surgery, National Cancer Institute of Milan, Milan, Italy.

Abstract

At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. Five conflicting points were discussed: radicality of the peritonectomy procedure, cytoreduction of neoplastic nodules <2.5 mm, the timing of bowel anastomoses in relation to hyperthermic intraperitoneal chemotherapy (HIPEC) and indications of protective ostomies. According to the panel of experts a partial parietal peritonectomy restricted to the macroscopically involved regions could be indicated in all listed clinical conditions with the exception of peritoneal mesothelioma. No expert was of the opinion that a radical parietal peritonectomy is advisable irrespective of the disease being treated. All the experts agreed that electrovaporization of small (<2.5 mm) non-infiltrating metastatic nodules in the mesentery would be appropriate, even if theoretically
the HIPEC affords microscopic cytoreduction. The panel also agreed that in the closed technique for HIPEC administration the intestinal anastomoses should be fashioned after completion of the perfusion. Finally when considering the place for protective ostomies the experts voted for a flexible approach allowing the surgeon to exercise discretion for individual patients.

Keywords: peritoneal carcinomatosis, cytoreductive surgery, consensus

Glossary

oncology

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

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.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

intraperitoneal chemotherapy

(IPC) a form of regional chemotherapy; the flooding of the abdominal cavity with chemotheraputic drugs to target the cancer cells directly. It is sometimes heated to improve absorption of the anticancer drugs by the cancerous cells and because heat itself can kill cancer cells.

Baratti D, Kusamura S, Deraco M.

Department of Surgery, National Cancer Institute, Milan, Italy.

Abstract

Peritoneal surface malignancies (PSM) have been traditionally regarded as uniformly terminal conditions. The combination of cyto-reductive surgery and perioperative intraperitoneal chemotherapy has changed PSM management from palliation to possible cure. Due to the inherent differences in biological and clinical behavior, the optimal adaptation of comprehensive treatment to each PSM is still a matter of debate. A session of The Fifth International Workshop on Peritoneal Surface Malignancy (Milan, Italy, December 4-6, 2006) was committed to reach a consensus pertaining to conceptual and technical aspects of the loco-regional treatment of each PSM. The consensus developing process was based on principles of the Delphi method. A total of 103 international experts from 17 countries were included in six Working Groups (WG) for each of the following PSM: peritoneal mesothelioma, abdominal sarcomatosis, carcinomatosis of gastric, colo-rectal, appendiceal, and ovarian origin. Evidence reports were written by the respective WG. The main conflicting points (CP) regarding preoperative evaluation, patient eligibility, combined treatment methodology, postoperative follow-up and future investigational perspectives were summarized as a list of multiple-choice questions. Overall, 160 CP were identified. A consensus 51% of voters favoring one option was reached in 143/160 CP (89.4%). The general treatment guidelines and future investigational perspectives were defined.

Keywords: consensus, peritoneal surface malignancies, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, HIPEC

Glossary

oncology

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

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.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

intraperitoneal chemotherapy

(IPC) a form of regional chemotherapy; the flooding of the abdominal cavity with chemotheraputic drugs to target the cancer cells directly. It is sometimes heated to improve absorption of the anticancer drugs by the cancerous cells and because heat itself can kill cancer cells.

Goudar RK.

Department of Medicine, Division of Hematology, Medical Oncology and Cellular Therapy, Duke University Medical Center, Durham, NC, USA.

Abstract

Malignant pleural mesothelioma is a resistant form of lung cancer, and its incidence continues to rise in Europe and Australia. Until recently, chemotherapy had not been shown to be effective in the treatment of this slowly progressive disease. In 2004, the combination of pemetrexed and cisplatin was shown to induce high response rates in MPM. This article reviews the published literature describing the development and testing of this therapeutic combination in mesothelioma, and examines in detail the key phase III clinical trial that led to the approval of pemetrexed by the US FDA. Ongoing research will further define the role of pemetrexed plus cisplatin in the treatment of MPM.

Keywords: malignant pleural mesothelioma, mesothelioma, pemetrexed, cisplatin

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.

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.

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.

Tran TA, Holloway RW, Finkler NJ.

Department of Pathology, Florida Hospital Orlando, Orlando, Florida 32803, USA. trannguyentienanh@hotmail.com

Abstract

Atypical/florid mesothelial hyperplasia associated with another neoplastic process is not an infrequent phenomenon and has been reported in a variety of tumors. In those instances, the mesothelial proliferation might create a misdiagnosis of metastatic carcinoma but seldom raises the possibility of a well-differentiated mesothelioma seeded by metastatic neoplastic cells. Herein, we report the case of a 40-year-old woman originally diagnosed with exuberant atypical mesothelial hyperplasia after an diagnostic laparoscopy. The subsequent operation, however, demonstrated a mucinous neoplasm of the appendix with involvement of the peritoneal cavity in the form of peritoneal mucinous carcinomatosis as well as metastases to the uterine serosa and adnexal surfaces. Microscopic analysis revealed an appendiceal adenocarcinoma with signet-ring-cell features that has metastasized to a diffuse well-differentiated mesothelioma of the peritoneal cavity. In many areas, the atypical mesothelial proliferation is indistinguishable from florid mesothelial hyperplasia. The true nature of the mesothelial proliferation was only confirmed after extensive additional sampling, which showed unequivocal stromal invasion. To the best of our knowledge, this is the first report of a metastatic appendiceal mucinous adenocarcinoma to a well-differentiated diffuse mesothelioma of the peritoneal cavity. Although commonly associated with atypical/ florid mesothelial hyperplasia, a carcinoma can rarely metastasize to a well-differentiated mesothelioma, which can pose significant diagnostic difficulties because it can mimic a reactive process. This unusual case report expands the spectrum of mesothelial proliferation in conjunction with a malignant neoplasm and serves to remind pathologists that such a concomitant occurrence exists.

Glossary

adenocarcinoma

(add-en-o car-sin-o-muh). Cancer that starts in the glandular tissue, such as in the ducts or lobules of the breast.

neoplasm

(nee-o-plas-um) an abnormal growth (tumor) that starts from a single altered cell; a neoplasm may be benign or malignant. Cancer is a malignant neoplasm.

hyperplasia

(hy-per-PLAY-zuh) too much growth of cells or tissue in a specific area, such as the lining of the breast ducts or the prostate. By itself, hyperplasia is not cancerous, but when there is a lot of growth or the cells are not like normal cells, the risk of cancer developing is greater.

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.

carcinoma

(car-sin-o-ma) a malignant tumor that begins in the lining layer (epithelial cells) of organs. At least 80% of all cancers are carcinomas.

atypical

(A-tip-uh-kul) not usual; abnormal. Often refers to the appearance of cancerous or precancerous cells. (See also hyperplasia.)

mesothelioma

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

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

Kim DS, Lee SG, Jun SY, Kim KW, Ha TY, Kim KK.

Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.

Abstract

The following reports a rare case of primary localized malignant mesothelioma of the liver. A 53-year-old man with no history of exposure to asbestos was admitted to our department for evaluation of incidentally detected liver mass. Computed tomography and hepatic angiogram showed a tumor at the dome of the liver, which was fed mainly through the inferior phrenic artery. The mass was resected, including a portion of the diaphragm. Microscopically, the tumor was composed of cord-like or trabecular arrangements of epithelioid cells having abundant eosinophilic cytoplasm and prominent nucleoli. Immunohistochemically, the tumor cells were strongly positive for calretinin and cytokeratin 5 and negative for hepatocyte markers. These findings were consistent with our diagnosis of epithelioid mesothelioma. A local recurrence was noted 15 months after surgery, which was treated by radiofrequency ablation. At 23 months after initial surgery, locally recurrent masses with direct invasion of the diaphragm and a solitary intrahepatic metastasis were noted, which was treated by partial excision of the diaphragm with intraoperative RFA after transarterial chemoembolization.

Glossary

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.

metastasis

(meh-tas-teh-sis) the spread of cancer cells to distant areas of the body by way of the lymph system or bloodstream.

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.

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.

Yan T, Sugarbaker P.

Peritoneal Surface Malignancy Program, Washington Cancer Institute, Washington Hospital Center, Washington, DC 20010, USA.

Abstract

Aims and Background: Diagnostic technologies which penetrate the abdominal wall in an attempt to definitively diagnose an intraabdominal malignancy by biopsy can contaminate the abdominal wall by cancerous cells. With follow-up these entrapped cancer cells may progress as an abdominal wall recurrence of the disease process. Frequently, laparoscopy is the definitive diagnostic study which results in the abdominal wall cancer progression.

Methods: We examined recurrences within the abdominal wall and attempted to establish a surgical approach to this problem which would maximize a functional result and minimize the incidence of disease persistence within the abdominal wall.

Results: Eighteen patients with abdominal wall recurrence were studied. Laparoscopy port sites resulted in the abdominal wall disease in eight patients, in four the recurrence was at a previous ostomy site, in three it was in a Pfannenstiel incision and in three it was in a McBurney incision site. All of these patients were treated by total resection of the rectus abdominis muscle. This resulted in a complete removal of visible disease that was dissecting along the fibers of the rectus abdominis muscle.

Conclusions: No patients required reoperation for abdominal wall hernia and mesh repair was not used in any of these patients. Disease control within the abdominal wall has been excellent.

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.

ostomy

(os-to-me) a general term meaning an opening, especially one made by surgery. See also colostomy, ileostomy, urostomy, and tracheostomy.

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.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

Yildirim H, Metıntaş M, Ak G, Dündar E, Ergınel S.

Department of Chest Diseases, Faculty of Medicine, Osmangazi University, Eskişehir, Turkey. heylul2002@yahoo.com.

Abstract

Almost all cancers can cause distant pleural metastases. However, pleural metastases of soft tissue sarcoma that constitute less than 1% of adult solid malignancy are extremely rare. It is very difficult to distinguish them form sarcomatous malignant mesothelioma on histopathological features. We report a 57 year-old man who presented to us with left chest pain and progressive dyspnea and was diagnosed to have a pleural metastases of soft tissue sarcoma by thoracoscopic biopsy.

Glossary

sarcoma

(sar-co-muh) a malignant tumor growing from connective tissues, such as cartilage, fat, muscle, or bone.

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.

tissue

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

mesothelioma

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