Ana Slipicevic, MSca, Geir Frode Øy, MScb, Inger Cecilie Askildt, BSca, Arild Holth, BSca, Ellen Hellesylt, BSca, Vivi Ann Flørenes, PhDa, Ben Davidson, MD, PhD

Division of Pathology, Norwegian Radium Hospital, Rikshospitalet Medical Center, N-0310 Oslo, Norway.

Abstract

We recently reported on higher expression of the insulin-like growth factor pathway genes IGF-II and IGFBP3 in serous ovarian/peritoneal carcinoma compared to malignant peritoneal mesothelioma. The present study analyzed the diagnostic and clinical role of these proteins in serous effusions. Effusions (n = 327), including 294 carcinomas (205 ovarian, 48 breast, 17 cervical/endometrial, 12 lung, 12 gastrointestinal/genitourinary) and 33 malignant mesotheliomas, were immunostained for insulin-like growth factor-II and insulin-like growth factor binding protein-3. Surgical ovarian carcinoma (n = 124) and peritoneal mesothelioma (n = 18) specimens were additionally studied. Insulin-like growth factor binding protein-3 levels were measured in 148 effusion supernatants (114 ovarian carcinomas, 18 breast carcinomas, 16 mesotheliomas) using enzyme-linked immunosorbent assay. Insulin-like growth factor binding protein-3 promoter methylation was analyzed in 11 ovarian carcinoma effusions. Insulin-like growth factor binding protein-3 (P = .002) and insulin-like growth factor-II (P < .001) expression by immunohistochemistry was significantly higher in carcinomas compared to mesotheliomas, with diagnostic sensitivity of 77% and 70% and specificity of 55% and 70%, respectively. In surgical specimens, insulin-like growth factor binding protein-3 expression was higher in ovarian carcinomas compared to peritoneal mesotheliomas (P = .007), whereas insulin-like growth factor-II expression was comparable (P = .505). Insulin-like growth factor binding protein-3 levels by enzyme-linked immunosorbent assay were comparable in the 3 analyzed cancer types. Insulin-like growth factor binding protein-3 promoter methylation was found in 6 of 11 effusions. High insulin-like growth factor binding protein-3 expression in prechemotherapy and high insulin-like growth factor-II expression in postchemotherapy ovarian carcinoma effusions correlated with poor overall survival (P = .031 and P = .024, respectively). Insulin-like growth factor-II expression in postchemotherapy effusions was an independent prognostic factor in Cox multivariate analysis (P = .04). In conclusion, insulin-like growth factor-II and insulin-like growth factor binding protein-3 are more frequently expressed in metastatic carcinomas compared to mesothelioma in effusions but are less specific than currently used markers. Insulin-like growth factor-II and insulin-like growth factor binding protein-3 may be novel prognostic markers in metastatic ovarian carcinoma.

Keywords: Insulin-like growth factor, Effusions, Carcinoma, Mesothelioma, Survival

Glossary

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.

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.)

Passot G, Cotte E, Brigand C, Beaujard AC, Isaac S, Gilly FN, Glehen O.

Service de chirurgie générale digestive et endocrinienne, centre hospitalier Lyon Sud (CHLS) – Lyon.

Abstract

Diffuse malignant peritoneal mesothelioma is a rare and lethal disease. Locoregional treatments combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) seem to improve prognosis.

Methods: Cytoreductive surgery and HIPEC was performed in 22 patients at the Centre Hospitalier-Lyon Sud between 1989 and 2006. A retrospective analysis of survival was carried out to assess clinical and histological prognostic factors.

Results: Nineteen patients with diffuse malignant peritoneal mesothelioma were included (16 epithelial, 3 biphasic and 3 multicystic forms). Sixteen patients presented stage 3 or 4 peritoneal carcinomatosis according to the Gilly classification. Optimal cytoreductive surgery was performed for 11 patients (complete macroscopic resection or residual tumor nodules less than 2.5mm). No post-operative deaths occurred but 9 patients (47%) presented grade III or IV post-operative complications. The overall median survival was 36.9 months; completeness of cytoreduction was the only significant prognostic factor.

Conclusion: Cytoreductive surgery combined with HIPEC may improve the length of survival for patients with diffuse malignant peritoneal mesothelioma; such patients should be treated in specialized centers.

Keywords: Peritoneal Mesothelioma , Treatment , Cytoreductive surgery , Hyperthermic intraperitoneal chemotherapy

Glossary

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.

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

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.

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.

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.

Moore AJ, Parker RJ, Wiggins J.

Department of Respiratory Medicine, Wexham Park Hospital, Wexham, Slough, Berkshire, UK. a.moore@ic.ac.uk

Abstract

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational “environmental” exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.

Glossary

prevalence

a measure of the proportion of persons in the population with a certain disease at a given time.

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.

benign

(be-nine) not cancer; not malignant.

mesothelioma

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

tunica vaginalis

The serous sheath of the testis and epididymis, derived from the peritoneum; it consists of outer parietal and inner visceral serous layers.

peritoneal

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

pleural effusion

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

ascites

(uh-sigh-tees) excess fluid accumulation in the abdominal (peritoneal) cavity.

Kaneko O, Gong L, Zhang J, Hansen JK, Hassan R, Lee B, Ho M.

Laboratory of Molecular Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Ovarian cancer and malignant mesothelioma frequently express both mesothelin and CA125 (also known as MUC16) at high levels on the cell surface. The interaction between mesothelin and CA125 may facilitate the implantation and peritoneal spread of tumors by cell adhesion, whereas the detailed nature of this interaction is still unknown. Here, we used truncated mutagenesis and alanine replacement techniques to identify a binding site on mesothelin for CA125. We examined the molecular interaction by Western blot overlay assays and further quantitatively analyzed by enzyme-linked immunosorbent assay. We also evaluated the binding on cancer cells by flow cytometry. We identified the region (296-359) consisting of 64 amino acids at the N-terminal of cell surface mesothelin as the minimum fragment for complete binding activity to CA125. We found that substitution of tyrosine 318 with an alanine abolished CA125 binding. Replacement of tryptophan 321 and glutamic acid 324 with alanine could partially decrease binding to CA125, whereas mutation of histidine 354 had no effect. These results indicate that a conformation-sensitive structure of the region (296-359) is required and sufficient for the binding of mesothelin to CA125. In addition, we have shown that a single chain monoclonal antibody (SS1) recognizes this CA125-binding domain and blocks the mesothelin-CA125 interaction on cancer cells. The identified CA125-binding domain significantly inhibits cancer cell adhesion and merits evaluation as a new therapeutic agent for preventing or treating peritoneal malignant tumors.

Glossary

mutation

a change; a change in a gene.

flow cytometry

(flow cy-tom-uh-tree) a test of tumor tissue to see how fast the tumor cells are reproducing and whether the tumor cells contain a normal or abnormal amount of DNA. This test is used to help predict how aggressive a cancer is likely to be. (See also ploidy, DNA, S-phase fraction.)

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.

antibody

a protein in the blood that defends against foreign agents, such as bacteria. These agents contain certain substances called antigens. Each antibody works against a specific antigen. (See also antigen.)

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.)

Baratti D, Kusamura S, Cabras AD, Dileo P, Laterza B, Deraco M.

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

Abstract

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 < or =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 < or =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.

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

oncology

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

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.

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.

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.

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.

jejunum

the section of the small intestine between the duodenum and the ileum.

Miao N, Pingpank JF, Alexander HR, Royal R, Steinberg SM, Quezado MM, Beresnev T, Quezado ZM.

Department of Anesthesia and Surgical Services, National Institutes of Health Clinical Center, National Institutes of Health, 10 Center Drive, MSC-1512, Building 10, Room 2C624, Bethesda, MD 20892-1512, USA.

Abstract

Cytoreductive surgery and continuous hyperthermic peritoneal perfusion (CHPP) involve the conduct of a complex surgical procedure and delivery of high-dose hyperthermic chemotherapy to the peritoneum. This therapeutic modality has been shown to benefit patients with peritoneal carcinomatosis resulting from gastrointestinal and ovarian tumors and mesothelioma. However, it is unknown whether the primary disease (mesothelioma versus peritoneal carcinomatosis) affects hemodynamic and metabolic perturbations during the course of CHPP with cisplatin. We examined the perioperative course of patients undergoing CHPP with cisplatin and evaluated the effect of primary diagnosis (mesothelioma versus peritoneal carcinomatosis) on hemodynamic and metabolic parameters in response to peritoneal perfusion. Sixty-nine mesothelioma and 100 peritoneal carcinomatosis patients underwent 169 consecutive cytoreduction and CHPP procedures with general anesthesia. During CHPP, patients from both groups developed significant increases in central venous pressure, and heart rate, decreases in mean arterial pressure (all P < 0.0001), metabolic acidosis with significant decreases in pH and bicarbonate (P < 0.0001), deterioration of gas exchange with significant increases in PaCO₂ and oxygen alveolar–arterial gradient (P < 0.0001), and significant increases in activated partial thromboplastin time (aPTT) and prothrombin time (PT) and decreases in hematocrit and platelet counts (all P < 0.0001). However, patients with mesothelioma had lesser increases in temperature (P < 0.01) and heart rate (P < 0.0001) and lesser decreases in hematocrit (P = 0.0013) during CHPP and greater decreases in sodium bicarbonate (P = 0.0082) after completion of CHPP compared with patients with peritoneal carcinomatosis. We conclude that the transient hemodynamic and metabolic perturbations associated with cytoreductive surgery and CHPP with cisplatin can vary according to the primary diagnosis (mesothelioma versus peritoneal carcinomatosis) warranting this therapy.

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.

platelet

a part of the blood that helps it "stick together" (clot) to promote healing after an injury. Chemotherapy can cause a drop in the platelet count--a condition called thrombocytopenia.

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.

anesthesia

(an-es-thee-zha) the loss of feeling or sensation as a result of drugs or gases. General anesthesia causes loss of consciousness ("puts you to sleep"). Local or regional anesthesia numbs only a certain area.

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.)

Carteni G, Manegold C, Garcia GM, Siena S, Zielinski CC, Amadori D, Liu Y, Blatter J, Visseren-Grul C, Stahel R.

Cardarelli Hospital, Medical Oncology, Via Cardarelli 9, 80100 Naples, Italy. giacomo.carteni@ospedalecardarelli.it

Abstract

Aim: Peritoneal mesothelioma (PM) has rarely been studied. The Expanded Access Program (EAP) provided access to 109 patients with PM.

Methods: This was a nonrandomized, open-label study conducted in chemo-naïve or previously treated patients with PM not amenable to curative surgery. Patients received pemetrexed (PEM) 500mg/m2 alone or with cisplatin (CIS) 75mg/m2 or carboplatin (CARBO) AUC 5 every 21 days, supplemented with standard vitamin B12, folate, and dexamethasone.

Results: Response rates (95% CI) for PEM, PEM/CIS, and PEM/CARBO were 12.5% (3.5, 29.0), 20.0% (7.7, 38.6), and 24.1% (10.3, 43.5), respectively. Median survival for PEM was 10.3 months. One-year survival rates for PEM/CIS and PEM were 57.4% (95% CI: 10.3, 100) and 41.5% (95% CI: 4.6, 78.4), respectively, and were not available for PEM/CARBO. Anemia was the most common serious adverse event (6.4%). Neutropenia (34.6%) was the most frequent CTC grade 3 or 4 toxicity reported.

Concluding statement: PEM with or without a platinum agent was both active and well tolerated in patients with peritoneal mesothelioma.

Keywords: Peritoneal mesothelioma, Pemetrexed, Platinum, Cisplatin, Carboplatin, Compassionate-use program, Expanded Access Program (EAP).

Glossary

oncology

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

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

cancer

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

anemia

(uh-neem-ee-uh) low red blood cell count.

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.)

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.

Chua TC, Yan TD, Morris DL.

Department of Surgery, University of New South Wales, St George Hospital, Kogarah, Sydney, NSW, Australia.

Abstract

Aims: Peritoneal mesothelioma is a rapidly progressing malignancy with a median survival of 6-12 months. Palliative surgery, chemotherapy and radiotherapy are futile and have not shown to improve survival. This paper reports the outcomes of cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of this disease.

Patients and Methods: An observational study of 20 patients with peritoneal mesothelioma treated with CRS and HIPEC at the St George Hospital, Sydney, Australia. Survival analysis was performed using the Kaplan-Meier method and comparison using the Log Rank test.

Results: There were six females. The mean age was 55.7 (9.0) years. The median survival was 29.5 (0.46-87.2) months with 1- and 3-year survival of 78.2% and 46.3%, respectively. Survival was found to be influenced by completeness of cytoreduction (P = 0.02) and histological subtype (P = 0.01). Patients with epitheloid peritoneal mesothelioma who had a CC0 had a median survival of 87.2 months.

Conclusion: CRS and HIPEC is a treatment option for peritoneal mesothelioma. Patients with epithelioid tumor who undergo complete cytoreduction may potentially benefit from this procedure.

Keywords: cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, mesothelioma, peritoneal neoplasms, peritonectomy

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.

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.

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.

Shukla S, Pujani M, Singh SK.

Department of Pathology, Lady Hardinge Medical College and Smt. Sucheta Kriplani Hospital, New Delhi, India.

Abstract

Ectopic decidual reaction is commonly seen in the ovary and cervix; however, peritoneal localization is rare. Peritoneal deciduosis is usually an incidental histological finding. It may present a diagnostic dilemma by mimicking grossly peritoneal carcinomatosis or tubercles and deciduoid mesothelioma, microscopically. We report three cases of ectopic decidual reaction discovered incidentally during caesarian sections, as whitish yellow nodules resembling tubercles. Histology revealed extensive decidualisation. To the best of our knowledge, this is the first report of ectopic decidua mimicking peritoneal tubercles.

Glossary

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.)

Foster JM, Gatalica Z, Lilleberg S, Haynatzki G, Loggie BW.

Division of Surgical Oncology, Creighton University Medical Center, Creighton University, Omaha, NE 68131, USA. jasonfoster@creighton.edu

Abstract

Malignant peritoneal mesotheliomas (MPM) are rare tumors representing 20% of all malignant mesothelioma cases. The median survival for these tumors is less than a year, and like other peritoneal surface malignancies, this is due primarily to intra-abdominal recurrence and progression. Currently there is a paucity of information about the biology of these tumors and molecular perturbations that are involved in tumor formation. Elucidation of mutations and biological pathways active in these tumors may identify valuable prognostic markers, as well as facilitate the development of novel therapies. In this study, we investigate the predictive value of epidermal growth factor receptor (EGFR) mutations in achieving optimal resectability. Twenty-nine patients with MPM were evaluated at a single tertiary care center and their tumors were probed for point mutations in the catalytic TK domain of epidermal growth factor receptor (mut+). All specimens were examined for somatic mutations by polymerase chain reaction amplification, and all variants were confirmed by multiple independent amplifications. Twenty-five patients were treated with cytoreductive surgery with or without intraperitoneal hyperthermic chemotherapy and complete clinical data including age, sex, cytoreductive score, mutation, and survival were available for comparison of the mut+ and mut- groups. The median age was 56 years, 71% of the patients were male, and the median follow-up time was 14.5 months. Mutations were found in 31% (9 of 29) of the tumors. Seven of these mutations were novel, and one was the L858R mutation described in non-small-cell lung cancer. Of the 25 patients managed surgically, 7 had mut+ and 18 wild type (mut-) disease. Optimal resectability was achieved in 7 (100%) of 7 of mut+ group and 9 (50%) of 18 mut- (p = .026). All mut+ patients are alive with a mean follow-up time of 24 months, whereas 5 (28%) of 18 of the mut- group are dead of disease with a mean follow-up time of 7 months (p = .27). In an analysis of covariance model, only optimal resectability (p = .04) was found to be predictive of survival. EGFR-TK seems to be a common site for mutation in MPM, with mutations being identified in 31% of patients. The EGFR mutations identified included the L858R activating mutation, as well as eight novel EGFR-TK catalytic domain point mutations. These mutations were predictive of optimal resectability, which was the only variable found to be predictive of survival. With longer follow-up, mut+ may not only be predictive of survival but may represent a subset of patients whose disease may be responsive to TK-inhibitor therapy. Experiments confirming the activating properties of the novel mutations are warranted.

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.

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.

oncology

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

mutation

a change; a change in a gene.

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.

cancer

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

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.

peritoneal

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

epidermal growth factor receptor

The process of cell division, growth, differentiation and death is a highly regulated process. Several class of trans membrane receptors play a pivot role in this process, of these, epidermal growth factor receptor (EGFR) a member of Receptor Tyrosine Kinase (RTK) family are best known. These comprises of four receptors Erb B1/HER 1, Erb B2 / HER 2, Erb B3/ HER 3, and Erb B4 / HER 4. Of these HER 2 is the most favoured target. (Source: Manoj Pandey and K Chandramohan)