Archive for the ‘Epithelial Mesothelioma’ Category

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Immunohistochemical and Ultrastructural Features of Mesothelioma

Immunohistochemical and Ultrastructural Features of Mesothelioma

Another interesting study is called, “Lymph Node Metastasis: as the Initial Manifestation of: Malignant Mesothelioma: Report of Six Cases” by Sussman, Jeffrey M.D.; Rosai, Juan M.D.  Here is an excerpt: “Abstract – We present six cases in which lymphadenopathy was the initial manifestation of malignant mesothelioma. In five cases, the primary tumor was located in the peritoneum; it was located in the pleura in the sixth. The involved lymph nodes were cervical in four cases, mediastinal in one, and inguinal in one. The morphologic, immunohistochemical, and ultrastructural features were typical of malignant epithelial mesothelioma. A review of the literature disclosed only one previously documented example of this phenomenon. When confronted with a lymph node involved by metastatic tumor, pathologists should be aware that malignant mesothelioma can present initially in the form of lymphadenopathy and include this possibility in the differential diagnosis.”

Another interesting study is called, “Induction Chemotherapy, Extrapleural Pneumonectomy, and Postoperative High-Dose Radiotherapy for Locally Advanced Malignant Pleural Mesothelioma: A Phase II Trial” by Flores, Raja M. MD; Krug, Lee M. MD; Rosenzweig, Kenneth E. MD; Venkatraman, Ennapadam PhD; Vincent, Alain BS; Heelan, Robert MD; Akhurst, Tim MD; Rusch, Valerie W. MD – Journal of Thoracic Oncology: May 2006 – Volume 1 – Issue 4 – pp 289-295.  Here is an excerpt: “Abstract – Introduction: Extrapleural pneumonectomy (EPP) and adjuvant high-dose radiation therapy (RT) are associated with a median survival of 3 years in early-stage malignant pleural mesothelioma (MPM) but of less than 1 year in locally advanced disease. Although local control after EPP and RT is excellent, most patients die of distant metastases. We designed this clinical trial to test the feasibility of induction chemotherapy followed by EPP and RT in locally advanced MPM with the ultimate aim of improving survival.

Methods: Patients with MPM and stage III or IV disease were eligible. Induction therapy was four cycles of gemcitabine and cisplatin. Patients without disease progression by computed tomography underwent EPP followed by adjuvant hemithoracic RT (54 cGy).

Results: From January 2002 to January 2004, 21 patients (17 men, four women; median age 60 years) were entered into the study. Histology was epithelioid in 14 patients and mixed or sarcomatoid five patients. Pretreatment disease stage was III in 13 patients and IV in six patients. Nineteen patients received induction chemotherapy. Response to induction therapy was complete in zero patients, partial in five patients, stable disease in six patients, and progression of disease in eight patients. Eight of nine patients undergoing surgical exploration had EPP. The median survival of all patients was 19 months. Patients who had an EPP had a median survival of 33.5 months. Patients with unresectable tumors had a median survival of 9 months (p = 0.01).”

Another interesting study is called, “Prognosis in malignant mesothelioma related to MIB 1 proliferation index and histological subtype.” By Beer TW, Buchanan R, Matthews AW, Stradling R, Pullinger N, Pethybridge RJ. – Department of Histopathology, The Royal Hospital, Haslar, Hampshire, England.  Hum Pathol. 1998 Mar;29(3):246-51.
Here is an excerpt: “Abstract – The aims of this study were to evaluate the use of the proliferation marker MIB 1 and histological subtype as indicators of prognosis in malignant mesothelioma. Sections from 41 cases of malignant mesothelioma were histologically subtyped on hematoxylin and eosin sections and stained immunohistochemically for the proliferation marker MIB 1. A proliferation index was derived and the results compared with patient survival data. A statistically significant difference was found between the survival of patients having a low and high MIB 1 index (P < .001). Patients with tumors having a low MIB 1 index lived significantly longer than those with a high MIB 1 index. Patients with the spindle cell histological subtype of malignant mesothelioma had significantly shorter survival times than those with the epithelioid or mixed tumors (P < .01). The MIB 1 proliferation index and histological tumor subtype are useful markers of prognosis in malignant mesothelioma.”

We all owe a debt of gratitude to these fine researchers for their work.  If you found any of these excerpts helpful, please read the studies in their entirety.

 

Monty Wrobleski is the author of this article.  For more information please click on the following links

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Various cancer malignancy cells have various characteristics and growth patterns

Various cancer malignancy cells have various characteristics and growth patterns

Malignant Mesothelioma cancer therapy programs depend on numerous elements which primarily consist of the mapping of the stage at which the cancer malignancy is and the extent to which it has spread. It also depends on the location in the body that has been affected. Various most cancers cells have various characteristics and growth patterns and this as well governs the therapy program. Most importantly, the age and the complications of the individual also require to be regarded.

What is Mesothelioma cancer?

There are numerous kinds of cancers and Mesothelioma cancer is 1 of them. This kind of cancer attacks the lungs and the cavity in the chest. It is a type of most cancers that is caused by the exposure to asbestos and consequently it is also termed as asbestos lung cancer. In this form of cancer malignancy tumors are formed in the mesothelial cells which actually guard the lungs, abdominal organs and also the heart by building a protective shield.
Mesothelioma takes numerous many years to really develop and manifest symptoms. At present each and every year there are about 300 cases that are reported the world over and these numbers are expected to improve to about 300.000 by the year 2030. It mostly impacts men who are above the age of 40 years. The Mesothelioma cancer lifestyle expectancy is narrowed down to less than two a long time.

Different kinds of Mesothelioma cancer

The initial type is called Epithelial Mesothelioma cancer which is a rare kind of malignant Mesothelioma cancer. This cancer influences the inner membrane of the cavity in the chest, heart, abdominal cavity and lungs. In this sort of cancer malignancy there are three forms; the first a single becoming Pleural Mesothelioma cancer. This kind is the most generally seen 1 and it impacts the Pleura which is the membrane that exists in in between the cavity of the chest and the lungs. This has two types and 1 of them is a Malignant Mesothelioma. The Peritoneal Mesothelioma cancer and Pericardial Mesothelioma cancer are outcomes of the infection and get malignant in no time at all. The mesothelioma cancer existence expectancy in this case is much much less than that of the other cancers.

Is Malignant Mesothelioma the exact same as lung most cancers?

Mesothelioma cancer or cancer of the lung lining is diverse from lung cancer malignancy. This lining is referred to as mesothelium and that is the reason why the condition is termed as Mesothelioma cancer. Though the principal trigger of Mesothelioma is the exposure to asbestos, it is not the only lead to. When the cancer spreads to other organs and it is termed as malignant and might not often be simply because of asbestos.
The Mesothelioma cancer existence expectancy is a lot less than that of lung most cancers. There are 3 phases in this sort of most cancers and they are measured by the Butchart, TNM and Brigham techniques. Each and every of these techniques has various stages for diagnosing the cancer malignancy. Every of them have four phases with the very first stage becoming the diagnosis and the last stage becoming mapping of the spread of the cancer malignancy to other organs. Clinical staging is pivotal to comprehend the onslaught and take the necessary action, including legal assistance for compensation.
www.mesothelioma-on-line.co.cc

Boston

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Mesothelioma Prognosis – What Are Your Chances?

Mesothelioma Prognosis – What Are Your Chances?

About 2000 to 3000 new cases of mesothelioma are diagnosed each year in the United States. Once a patient receives a diagnosis of this cancer, his or her physician will most likely discuss the prognosis or probable course and outcome of the disease with the patient.

Factors That Determine Prognosis

Most times a diagnosis of mesothelioma is made when the cancer has reached an advanced stage as it usually takes a very long amount of time after the contact with asbestos before most victims start displaying the symptoms associated with the disease.

In addition to this fact, even when the symptoms of this cancer do eventually surface, they often resemble the symptoms of more general diseases like pneumonia, influenza and some other lung diseases. This fact coupled with the long delay in appearance of symptoms makes the accurate diagnosis of mesothelioma a very difficult one.

Thus as result of these factors, prognosis for majority of the patients is poor, but many doctors recommend treatment options like surgery, chemotherapy, and radiotherapy to help combat the disease.

Factors that affect prognosis include:

A} The stage of the cancer:

Medically the progression of the cancer is classified in form of stages. The stages range from stage one to stage four. The higher the stage the, the more advanced the cancer. Unfortunately, once the cancer has reached stages three to stage four, treatment options become limited and less effective. In stage four of the cancer, the cancer has spread to other parts of the body and the tumor has often deeply eaten into various key organs and tissues in the body. Stage 4 is not suitable for surgery. Generally the higher the stage of the cancer the worse the prognosis.

B} Histological type of cancer:

Histology refers to the basic cell structure and type of the cancer. Histologically, there are four types of mesothelioma:a}Epithelial,b}Sarcomatoid c}Biphasic{mixed} d}Desmoplastic{variant of sarcomatoid}
Epithelial mesothelioma has a better prognosis than the other types and the sarcomatoid form has the worst prognosis.

C} Age and general condition of victim

Malignant mesothelioma is often diagnosed in people above the age of 55 years old, although there may be exceptions. So some of the victims would have developed chronic diseases associated with old age like diabetes and hypertension and this worsens their prognosis.

D} The size of the tumor

E} The location of the tumor and whether the tumor is operable{whether it can be removed surgically}

F} The extent of other symptoms, including fluid in the lungs or abdomen.

G} Whether or not the patient is a smoker.

When discussing the survival rate of any cancer, references are often made to the “five year survival rate”. The five year survival rate refers to the percentage of patients who live at least five years after receiving their diagnosis. According to the American Cancer Society, the five year survival relative survival rate for mesothelioma is approximately 10%.The number has improved over the last five years up from the 9% reported at the end of 2002.
In general, the average length of survival reported throughout the last five years has been 10-11 months after diagnosis.

Bello Kamorudeen .For more information on mesothelioma go to http://www.mesotheliomacorner.blogspot.com


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Mesothelioma from Metastatic Adenocarcinoma

Mesothelioma from Metastatic Adenocarcinoma

Another interesting study is called, “Value of the Mesothelium-Associated Antibodies Thrombomodulin, Cytokeratin 5/6, Calretinin, and CD44H in Distinguishing Epithelioid Pleural Mesothelioma from Adenocarcinoma Metastatic to the Pleura” by P M Cury M.D., D N Butcher, C Fisher M.D., B Corrin M.D. and A G Nicholson D.M. – Mod Pathol 2000;13(2):107–112.  Here is an excerpt: “Abstract – Until recently, the standard approach of most laboratories in distinguishing epithelioid pleural mesothelioma from metastatic adenocarcinoma has been a negative result from a panel of adeno-carcinoma-associated antibodies. However, several “mesothelium-associated” antibodies have been proposed as useful in this situation, and we have applied four of these putative mesothelioma markers—thrombomodulin, cytokeratin 5/6, calretinin, and CD44H—to a series of 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas with known primary sites (lung = 19; breast = 21; ovary = 6; colon = 10; kidney = 4; uterus, epididymis, pancreas = 1 case each). Of the mesotheliomas, 55 of 61 (90%) stained for thrombomodulin, 56 of 61 (92%) for cytokeratin 5/6, 47 of 51 cases (92%) were positive for calretinin, and 39 of 43 (91%) were positive for CD44H. Of the metastatic adenocarcinomas, 12 of 63 (19%) cases were positive for thrombomodulin, 9 of 63 (14%) were positive for CK5/6, and 27 of 60 (45%) were positive for CD44H. With calretinin, only 1 case of 59 (2%) showed positive nuclear staining. All four antibodies stained reactive mesothelium; thrombomodulin also stained endothelium; and CD44H variably stained lymphocytes, macrophages, and fibroblasts. We conclude that all four antibodies show high sensitivity for epithelioid mesothelioma, but only calretinin (98%), cytokeratin 5/6 (86%), and thrombomodulin (81%) show sufficient specificity for practical use in this situation.”

Another interesting study is called, “Surgical treatment of pleural Mesothelioma” by PM McCormack, F Nagasaki, BS Hilaris and N Martini – The Journal of Thoracic and Cardiovascular Surgery, Vol 84, 834-842.  Here is an excerpt: “From 1939 through 1981, 170 patients were seen and treated for pleural mesothelioma. Twenty-one tumors were benign, 47 were fibrosarcomatous, and 102 were epithelioma. Resection was the main mode of treatment in benign and fibrosarcomatous mesothelioma. Treatment of diffuse epithelial mesothelioma presented the greatest challenge. Surgical therapy, radiation therapy, and chemotherapy were used in combination in these patients. The review of our patients treated prior to 1972 had shown no benefit from including pulmonary resection in the surgical treatment of these tumors. Since then, all patients with diffuse mesothelioma were treated by pleurectomy without pulmonary resection. Both internal and external radiation therapy were also used to enhance local control. Forty-nine percent of patients with epithelial mesothelioma lived 1 year. The median survival in patients whose disease was controlled by these methods was 21 months. Despite the poor prognosis in malignant mesothelioma, better controlled by these methods was 21 months. .”

Another interesting study is called, “RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma.” By Shimizu E, Coxon A, Otterson GA, Steinberg SM, Kratzke RA, Kim YW, Fedorko J, Oie H, Johnson BE, Mulshine JL, et al. – National Cancer Institute-Navy Oncology Branch, National Cancer Institute, Bethesda, Maryland 20889. – Oncogene. 1994 Sep;9(9):2441-8.  Here is an excerpt: “Abstract – We have studied RB protein expression in 171 cell lines derived from patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), pulmonary carcinoid, mesothelioma, and extrapulmonary small cell cancer (EPSC) and have correlated this data with clinical outcome. We detected absent or aberrant RB protein expression in 66/75 SCLC, 12/80 NSCLC, 1/6 carcinoid, 0/5 mesothelioma, and 4/5 EPSC samples. In addition, we observed integration of human papilloma virus (HPV) DNA in the single EPSC cell line that retained wildtype RB protein. We did not detect integration of HPV, SV40 or adenoviral DNA in other tumor samples with wildtype RB status. We also noted a stable, hypophosphorylated mutant RB in 12 SCLC and 3 NSCLC samples which might have been falsely interpreted as wildtype by current immunohistochemical techniques. Analysis of the matched clinical data showed no associations between RB status and age, sex, extent of disease, performance status, smoking history, and previous treatment. In addition, retrospective analyses showed no consistent correlation of RB protein expression with either best clinical response, overall survival, or in vitro chemotherapeutic drug sensitivity. The stable expression of RB after gene transfection into RB(-) SCLC cells, however, resulted in a trend toward increased in vitro resistance to etoposide, cisplatin and doxorubicin.”

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.

Monty Wrobleski is the author of this article.  For more information please click on the following links

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Online Second Opinion – Peritoneal Carcinosis of Undefined Nature

Online Second Opinion – Peritoneal Carcinosis of Undefined Nature

second opinion – Peritoneal Carcinosis of Undefined Nature

This is a summary of 57 years old patient that was interested with receiving an expert second opinion. When the patient was 2 years old he had appendectomy, at 9 years old – intestinal invagination operation affecting the right side and iliac fossa, with subsequent hardening of the scar and the appearance of a sub-scar asymptomatic mass, interpreted as a cicatricial reaction. When the patient was 38 Years old – Dupuytren and at 50 years old – Laparoscopic Cholecystectomy.

On December 2004 and several months later the patient suffered from intestinal sub-occlusion ileus. A colonoscopy was performed which was negative. On November 2005, a surgical intervention took place with the finding of an adhesion mass in mid right abdomen. 700 cc of brown exudates was drained. Right Hemi-Colectomy was preformed.

The sections that were macroscopically tested was an adhesive mass in the size of 8*10*6 cm found that consisted of the terminal iliem and the cecum at a length of 18 cm.

Microscopically the sections of the intestines were diagnosed (by the Histopathological and Cytodiagnostic laboratory at the Riunit hospital of Trieste) as Carcinoma of low grade differentiation. Same findings were found in adipose tissue with pseudo glandular aspects. Other parts of intestine showed the same microscpical appearance also with papillar aspects. Markers – negative (CEA-2.10, Ca19.-2.5, Ca125-5.4).

On CT: small amount of fluid. Modest evidence of peritoneal inflammation and some adhesions on abdominal wall.

Re-examination of the surgical material on Januarys 5th by the National Tumor Institute suggested the diagnosis of malignant Mesothelioma monophasic of epithelial type.

Conclusion: Patient with Epithelia Peritoneal Mesothelioma that experienced his first episode of intestinal sub-occlusion on 2004.

On the 01.10.06, the patient has undergone a new examination at the Clinical Pharmacology and New Pharmaceuticals Division of the European Institute of Oncology, whose anamnesis reports an. In December 2004 a sub-occlusive episode is reported, affecting the small intestine, which spontaneously healed. A CAT scan is performed, with irrelevant results. During summer 2005, the abovementioned episodes occur again and the patient undergoes a colonoscopy with irrelevant results.

In November 2005 he undergoes the examinations and operation we have mentioned in the previous report.

In light of the information above, the specialist suggests to await the results from new histology analyses and to repeat a thorax, abdomen and pelvis CAT scan.

Should the hypothesis of a mesothelioma be confirmed, it is suggested to consult the opinion of a colleague surgeon who is expert in peritonectomy and intraperitoneal hyperthermic treatments, as this is considered the most efficient approach.

In the alternative, it is suggested to monitor the clinical trend throughout time (CAT and PET scans after 3 months); however, only when presenting an evolving situation or if a clear pathology is denounced via the CAT scan, the specialist would suggest a systemic chemotherapy treatment.

On the other hand, should the histology be different, it is suggested to nonetheless repeat a CAT and a PET scan in a month, and, in absence of a clear primitiveness, it is advised to still consult the colleague surgeons for a peritonectomy.

The new histopathology examination performed at the European Institute of Oncology on the 01.11.2006 reports: “Evidence compatible with a malignant epithelial mesothelioma infiltrating the small intestine’s wall. Immunophenotype of the neoplastic population: positive as per calretinin, cytokeratin 5/6 and WT1; negative as per CDX-2, CEA 5 and desmin.”

Another histology examination performed at the Milan Cancer Institute on the 01.13.2006 reports: “Morphological and immunophenotypic pictures coherent with an epithelial type of malignant mesothelioma. Immunoreactivity: Calretinin +, CK 5/6 +, WT 180 +, CD31 -.”

The thoracic-abdominal CAT scan with contrast performed on the 01.16.2006 reports: “In the thorax area neither parenchymal nor pleural alterations are reported, nor mediastinal lymphadenopathies. In the abdominal region no focal hepatic lesions are appreciated, nor signs of dilation of the bile-duct subsequently to a cholecystectomy. A minimal perihepatic and perisplenic liquid layer is at all times appreciable, with a modest and homogeneous peritoneal inspissation of the suprahepatic and suprasplenic zones; pancreas, adrenal glands and kidneys in normal conditions (30mm cortical cyst with greater diameter between the middle third and the lower third of the right kidney); lymph nodal granules (with dimensions not exceeding one centimeter) in periaortocaval area and along the iliac femoral axis. Diffused and modest inspissation of the months, with ansae that appear slightly conglutinated and adhering to the abdominal wall and with a minor reduction in the transparency of the mesenterial adipose tissue, in a situation that could also be compatible with the sequence of repeated sub-occlusive episodes and the consequent surgical actions. In the pelvic hole, normally extended bladder, with regular walls; no abnormal tumefaction is evident.”

On the 01.20.2006, the patient finally visited the surgeon he had addressed to by the medical doctor who had examined him on the 01.10.2006, and the former procured the following conclusion:

“Patient with peritoneal epithelial mesothelioma that, by interpreting the first sub-occlusive episode in 2004 as secondary to such pathology, seems to date back to some time ago and appears with a low degree of biological malignity. The CAT scan seems to show diaphragmatic involvement and a significant adhesion syndrome between ansae and abdominal wall. In order to apply a precise surgical indication, an interview with the surgeon who operated the patient in November 2005 seems indispensable, so as to evaluate the involvement of the visceral peritoneum and above all of the small intestine, the latter being a true contraindication to a surgical approach.

The cytoreduction via chemo-hyperthermia, followed by systemic chemotherapy seems to be the best option (even though experimental). Should there be, on the other hand, doubts about the surgical indication, one would opt for systemic chemotherapy, eventually with neoadjuvant intention.

It is very important for the patient to know if there are other diagnostic procedures. Assuming the histological diagnosis is Peritoneal Mesothelioma, what is the recommended therapy and if there are experimental protocols, including immunotherapy.

The case was sent to Medical Opinion (www.m-opinion.com) for second opinion evaluation. The case was sent to senior professor from Tel Aviv University to review the case.

The professor assumed that the diagnosis was mesothelioma according to the various pathological reports. It is important to have immunohistochemical staining for c-kit, EGFR, VEGFR, PDGFR-alpha for possible targeted therapies.

The best treatment option for mesothelioma is radical surgery: peritonectomy + hyperthermic intra-operative administration of chemotherapy. However, it is hard to imagine the real intra-abdominal involvement by the tumor according to the descriptions given by the radiologists. It is recommended to review the CT scans and perform a PET -CT with FOG to locate all tumor sites.

If the tumor is inoperable, it is better to go for chemotherapy: cisplatin + pemetrexed (Alimta), or cisplatin + gemcitabine, as a palliative treatment or as a neo-adjuvant therapy.


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