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Antiphospholipid Syndrome (APS , APLS), also known as Antiphospholipid antibody syndrome or ‘Sticky blood Syndrome’or Hughes syndrome is a disorder characterized by elevated level of multiple different antibodies that are associated with arterial and venous thrombosis and pregnancy related complications. This syndrome occurs due to auto antibodies against phospholipids (aPL), a cell membrane substances. The antibodies are found against cardiolipin (anticardiolipin antibodies) and β2 glycoprotein I (β2 GP1).
These aPL antibodies were first seen in some patients with positive test for syphilis without infection out of which few developed SLE(Systemic Lupus Erythematosus ) and other similar conditions. Later lupus anticoagulant was detected in few cases of SLE. A case report in 1956 showed repeated pregnancy loss,thrombophlebitis and lupus anticoagulant. In 1980 the rheumatologist Dr. Graham R. V. Hughes of St. Thomas’ Hospital , London provided the details including the test for anticardiolipin antibodies. Later anticardiolipin antibodies were found to act against β2GP1,while lupus anticoagulant was found to act against β2GP1 and more recently prothrombin.
It can be classified as
1. Primary - without any related disease.
2. Secondary – in conjunction with autoimmune diseases like SLE .
3. Catastrophic APS (CAPS) – Rapid multi organ failure due to thrombosis leading to death.
Normal person may have antibodies. The triggering factors are:-
1. Infections- People with Syphilis ,HIV infection, Hepatitis C, Malaria.
2. Medications- Antihypertensive like hydralazine , antiepileptic like phenytoin, antibiotics like amoxicillin. Cocaine, procainamide, quinine may cause.
3. Genetics – Although APS has been reported to occur in multiple members of the same family, no clear inheritance pattern has been identified and no gene has been found to be the sole cause of this condition. One report in 1999 studied families with more than one affected member, examined possible modes of inheritance, and examined links with certain genes. In seven families 30 out of 101 family members met diagnostic criteria for the syndrome. The data were fitted best by either a dominant or co dominant models.
Antiphospholipid syndrome is an autoimmune disease in which “antiphospholipid antibodies”(Anticardiolipin antibodies and Lupus anticoagulant) react against protein that bind to anionic phospholipids on plasma membranes. Like many autoimmune diseases , it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid antibodies are associated with thrombosis and vascular disease.
Anti-ApoH and a subset of Anti-cardiolipin antibodies bind to ApoH , which in turns inhibits Protein C, a glycoprotein with regulatory function upon the common pathway of coagulation(by degrading [Va factor]).
LAC antibodies bind to prothrombin, thus increasing its cleavage in thrombin, its active forms.
In APS there are also antibodies binding to Protein S, which is a co-factor of protein C. Thus Anti-Protein S antibodies decrease Protein C efficiency.
Annexin A5, which forms a shield around negativity-charged phospholipids molecules, thus reducing their availability for coagulation. Thus Anti-annexin A5 antibodies increase phospholipids-dependent coagulation steps.
The Lupus anticoagulant antibodies are those that show the closest association with thrombosis, those that target β2GP1 have a greater association with thrombosis than those that target prothrombin. Anticardiolipin antibodies are associated with thrombosis at moderate to higher titres (> 40 GPLU or MPLU). Patients with both Lupus anticoagulation antibodies and moderate/high titer anticardiolipin antibodies show a greater risk of thrombosis than with one alone.
The aPL antibodies are found in 30% cases of SLE. The aPL antibodies may be found in 1-5% of normal individuals. There is no racial predisposition of Primary type. It is more common in young adults(30-45 yrs). Primary APS accounts for over 50% cases. Some studies indicate that aPL antibodies may play a role in approximately one third of strokes in persons under age of 50.A female predominance causing secondary APS parallels APS with SLE and other connective tissue disease .After age of 60 incidence is rare.
APS usually shows up for the first time as vascular thrombosis or embolism or as recurrent pregnancy loss. Thrombocytopenia , certain skin problems, neurological signs, heart valve disease and certain autoimmune diseases have also have been noted in association with APS. Pulmonary hypertension and sensory- neural hearing loss have been noted in some individuals with APS as well.
Conditions associated with APS include:
1. Systemic Vascular Thrombosis
While the deep veins of the legs are most frequent sites of thrombosis, thromboemblism can involve virtually any vein or artery. Deep vein thrombosis tends to be most common finding, occurring in half of affected individuals. Other sites of venous thrombotic events include the veins of the lungs (due to pulmonary embolism, a clot that typically has dislodged from a vein below the pulmonary veins and lodged in a pulmonary veins), thoracic veins(veins in or above the chest that carry blood to the heart including the superior vena cava, or jugular vein), and abdominal or pelvic veins.
A risk of recurrent thrombi is associated with APS as well. Most studies suggest that individuals who have a recurrent episode will have it in a similar blood vessel type. For example, indivisuals who have a stroke initially will most often have a stroke if they have a recurrence. Nonetheless, individuals are reported who have had different types of thrombosis events.
A deep vein thrombosis( DVT) can form in the arm or leg after a long journey, or in some women, after starting the contraceptive pill. Clots in the veins can cause thrombophlebitis of the legs with pain in the thigh or calf, swelling of the leg , and sometimes a visible red, thickening blood vessel. Damage to the valves of lower limbs may impair the upward venous flow leading to chronic venous insufficiency causing chronic swelling and discoloration of leg. Thrombosis can also affect vital organs such as the eye, liver and kidney.

2. Pregnancy Loss and Other Complications
APS is associated with miscarriages as well as other complications of pregnancy. Most studies have estimated the prevalence of aPL antibodies among pregnant women at 5 percent or less, most of these women do not have any signs or symptoms of APS. Around 10-20 percent of women with multiple pregnancy loses are thought to have APS.
Women with APS often have a history of recurrent (usually defined as three or more) pregnancy losses. Pregnancies occurring in women with APS are at increased risk of prematurity , slower than expected growth of the fetus, and preeclampsia. Pregnant women with APS are also more prone to develop deep vein thrombosis during pregnancy or puerperium .
One miscarriage is a disaster. Two is worse. Imagine the suffering of women who have 3,5,7 or even 12 pregnancy losses, and sometimes as late as the late few weeks of their pregnancy.
We now know that Hughes Syndrome is the most common treatable cause of recurrent miscarriage. Future more, late pregnancy loss, fortunately an unusual problem in pregnancy, is very strongly associated with Hughes Syndrome as is pre-eclampsia, placental abruption and intra-uterine growth restriction.
For the sake of a simple blood test, patients with miscarriage or late pregnancy loss can be tested for Hughes Syndrome. Treatment of these patients has proved one of the true success of modern medicine , the successful pregnancy rate rising from a previous low of fewer than 20% to figures now in the region of 75-80% success rate.
3. Thrombocytopenia
An association with immune thrombocytopenia has been established. This occurs to varying degrees in many as 50% of individuals with APS. Because platelets help the blood to clot, thrombocytopenia can sometimes cause a bleeding disorder in an otherwise healthy person as bleeding from gum, nose and skin. However in APS thrombocytopenia is usually moderate and is rarely significantly enough to cause bleeding complications or affect anticoagulant therapy.
4. Skin Disorders
Certain skin conditions have also been observed in APS. These include livedo reticularis (mottled discolouration of the skin), ulcers on the skin, usually on the legs, and sometimes skin necrosis .
Many Hughes Syndrome patients complain of ‘cold circulation’ and this sometimes manifest as a blotchy appearance of the skin of the arms and legs, described in medical textbooks as “livedo reticularis” or “corned beef skin”. It can also cause repeated sores and bumps (nodules) of the skin.
5. Stroke and Other Neurological Disorder
Stroke is associated with APS as are some other neurological conditions. In addition to cerebrovascular thrombosis , embolic stroke can also occur. Multiple strokes can sometimes leads to a condition called multi-infarct dementia.
Other neurological problems have been reported in people with aPL antibodies, although they are not as strongly associated with APS as stroke. These include seizures, chorea , migraines, Guillain-Barre syndrome, diabetic peripheral neurotherapy, transverse myelitis and conditions similar to multiple sclerosis. Evidence for an association with cognitive dysfunction is growing.
There are many cause of strokes- for instance hypertension but most surveys show that 1 in 5 young strokes (under the age of 45) are now associated with Hughes Syndrome(APS). Now, in the age of easy diagnoses of Hughes Syndrome, many patients are not receiving adequate anti-coagulant treatment of their “sticky blood” , and suffering from early mini-strokes or TIAs (transient ischemic attacks) or more permanent strokes.
Some people with Hughes Syndrome develop a syndrome which is very similar to multiple sclerosis where they have numbness or pins and needles, double vision or loss of part of the field of vision, and have difficulty in walking. Consequently one of the main alternative diagnosis in patients with Hughes syndrome is multiple sclerosis.
6. Heart Disease
A type of heart valve disease called Libman-Sacks endocarditic is sometimes seen in individuals with aPL antibodies. In this condition, growth on the heart can break off and travel through the blood streams, causing embolic events. Hughes Syndrome can lead to heart attacks and heart valve problems that can mimic bacterial endocarditic, and create clots in the upper chambers of the heart. Up to20% of young people (under 45) who have a heart attack have antiphospholipid antibodies.
7. Lupus and Other Autoimmune Disorder
APS is classified within the category of autoimmune disorders . Individuals with aPL antibodies sometimes have an additional autoimmune disorder, most commonly SLE. About 30-40 percent of individuals with SLE have elevated aPL antibodies. APS has also been associated with a number of other autoimmune disorders, including myasthenia gravis, Graves’ disease, autoimmune hemolytic anemia and Evan’s syndrome.
8. Headache or migraine
Often this is one of the major features of the illness. Sometimes the headaches disappear in the 20’s to return with a vengeance in the 30’s or 40’s. This is a most important feature of Hughes Syndrome and symptoms sometimes improve dramatically when treatment is started. Often migraine features such as flashing lights and zigzag patterns accompany the headaches found in Hughes Syndrome.
9. Giddiness
For reasons not completely understood the brain appears particularly sensitive to the clotting effects of antiphospholipid antibodies and one of the ways in which it reacts to “Sticky blood” affecting its oxygen supply is to cause balance disorders. Many patients complain of feeling giddy or “slightly drunk” and this can naturally lead to accidents.
10. Memory loss
When the brain is starved of oxygen it only has a limited number of ways of complaining and a common symptoms of Hughes Syndrome is memory loss. Many patients feel that they are developing Alzheimer’s disease when they can’t remember names of friends and family , forget their shopping lists and get their word and sentences muddled. One of the most dramatic observations is the improvement of the memory (and the disappearance of the headaches and ‘fog’) which patients observe when blood thinning medicine is started.
11. Visual disturbance
In addition to the flashing lights and zigzag patterns which can accompany headaches and migraines, the person with Hughes Syndrome can experience double vision or sudden visual loss. This can be caused by the brain reacting to disturbances in its supply of blood or by the veins and arteries in the eye being affected.
12. Pulmonary embolism
A pulmonary embolism occurs when a blood vessel supplying the lung becomes clogged up by a clot. Blood clots in the lung can cause chest pain, shortness of breath and rapid breathing. Repeated clots can cause pulmonary hypertension which may cause the person to be constantly short of breath. Larger emboli in the lungs can be lethal.
13. Gastrointestinal disorder
Hughes Syndrome can affect the blood supply to the intestine causing abdominal pain, fever and blood in the stool. Antiphospholipid antibodies can also cause a condition called Budd-Chiari syndrome, in which a blood clot prevents blood from flowing out of the liver and the person may then experience nausea, vomiting, jaundice, dark urine and the swelling of the abdomen.

Diagnosed on the basis of clinical and laboratory findings. History of episode of thrombosis and pregnancy loss is important.
Laboratory Test- APS is diagnosed if an individual experiences one or more episodes of thrombosis or pregnancy loss and if aPL antibodies are detected through laboratory testing of the individual’s blood.
There are two main types of antiphospholipid antibody tests- immunological tests, like the anticardiolipin ELISA (enzyme-linked immunoassay), and coagulation-based tests for the lupus anticoagulant. ELISA are immunologically based tests, or immunoassays in which an antigen-antibody reaction is used to detect the antibodies. In contrast, lupus anticoagulant tests detect antibodies based on their ability to slow down phospholipids-dependent clotting reactions. Most individuals with APS have antibodies that can be detected in both tests. However a significant percentage of patients are positive in one test but not the other. Therefore to diagnose APS it is standard practice for both tests to be performed. The tests are then repeated six to eight weeks later to confirm the presence of aPL antibodies.
Antiphospholipid syndrome is tested in the laboratory using both liquid phase coagulation assays(lupus anticoagulant) and solid phase ELISA assays (anti-cardiolipin antibodies).
Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Thus genetic thrombophilia screening can consists of :
• Future studies for Factor V Leiden variant and the prothrombin mutations. Factor VIII levels, MTHFR mutation.
• Levels of proteins C , free and total protein S, Factor VIII, antithrombin , plasminogen, activator(TPA) and plasminogen activator inhibitor-1(PAI-1)
The testing of antibodies to the possible individuals targets of aPL such as β2 GP1 and antiphosphatidyl serine is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though cardiolipin is not considered an in vivo target for antiphospholipid antibodies.
Lupus anticoagulant
This is tested for by using a minimum of two coagulation tests that are phospholipid sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged APTT that does not correct in an 80:20 mixture with normal human plasma(50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The APTT (plus 80:20 mix) , dilute Russell’s viper venom time(DRVVT), the kaolin clotting time (KCT), dilute thromboplastin time(TDT/DTT) or Prothrombin time(using a lupus sensitive thromboplastin) are the principal tests used for the detection of lupus anticoagulant. The tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion demonstrating persistent positively to allow a diagnosis of antiphospholipid syndrome. This is to prevent patient with transient positive tests (due to infection etc) being diagnosed as positive.
Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g. Factor VIII). This is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact pathways antibodies (Factor VIII, Factor IX, Factor XI and Factor XII). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iudl(35%) where as a specific factor antibody will rarely give a result higher than 10iudl(10%). Monitoring IV anticoagulant therapy by the APTR is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of factor Xa by Antithrombin in the presence of Heparin.
Anticardiolipin antibodies
These can be detected using an enzyme-linked immunosorbent assay(ELISA) immunological test which screens for the presence of β2GP1 dependent anticardiolipin antibodies(ACA).
A low platelet count and positively for antibodies against β2GP1 or phosphatidyl serine may also be observed in a positive diagnosis.
Clinical significance
Research in 2009 suggest elevated IgA anti-β2GPI antibody titers may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria, thus testing for IgA anti-β2GPI antibodies when other aPL tests are negative and APS is suspected may be in order.
The diagnosis of APS is made in case of a clinical event( vascular thrombosis or pregnancy event) and repeated positive tests of aPL performed 12 weeks apart( repeat aPL testing is necessary due to the naturally occurring presence of transient low levels of aPL following infections).
The Updated Sapporo APS Classification Criteria (1998,published in 1999)are commonly used for APS diagnosis.
Based on these criteria, APS diagnosis requires:
a).Vascular thrombosis (blood clots) in any organ or tissue or Pregnancy Event (one or more miscarriages after 10th week of gestation , three or more miscarriages before 10th week of gestation, or one more premature births before 34th week of gestation due to eclampsia) and
b).Persistency (6weeks apart) of positive aPL ( lupus anticoagulant test, moderate-to-high titer anticardiolipin antibodies or moderate-to-high titer β2GPI antibodies).

The International Consensus Statement is commonly used for Catastrophic APS diagnosis. Based on this statement CAPS diagnosis requires:

a) Vascular thrombosis in three or more organs or tissues
b) Development of manifestations simultaneously or in less than a week
c) Evidence of small vessel thrombosis in at least one organ or tissue
d) Laboratory confirmation of the presence of aPL.
Some serological tests for syphilis may be positive in aPL-positive patients (aPL bind to the lipids in the test and make it come out positive) although the more specific tests for syphilis that use recombinant antigens will be negative.
There is no cure but medications may reduce the risk of thrombosis. Despite our increased understanding of the syndrome the cornerstone of therapy remains antiaggregant and anticoagulant agents.
• Very ill patients requires hospitalization. Usually may be treated in outdoor. A variety of specialists are required.
• Desirable to limit blood coagulation including quitting smoking, ceasing oral contraceptives, control BP.
• In cases of P/H of thrombosis long-term medication like warfarin.
• In pregnant cases need treatment and monitoring to avoid complication.
• Treatment for APS must be individualized according to the person’s current health status and the types of problems that has experienced due to their APS. In general, for a person who has aPL antibodies and had a thrombotic event a short-term course of heparin is followed by long-term( sometimes life-long) treatment with warfarin.
In women with moderate to high levels of aPL antibodies and a history of pregnancy loss who wish to get pregnant again individualized. After consulting with obstetrician and rheumatologist and /or hematologist women generally begin treatment with heparin and low-dose aspirin. For those individuals who have been found to have aPL antibodies but no signs or symptoms of APS low-dose aspirin is generally recommended. Hydroxychloroquin(HCQ) an antimalarial drug used for Lupus and Rheumatoid arthritis is under trial.
If you or someone you know has been diagnosed with APS, we recommend talking with a health care provider to determine a personalized course of management.
APS is an autoimmune disease associated with arterial and/or venous thrombosis and pregnancy related complications. The antibodies responsible are anticardiolipin antibody, lupus anticoagulant and anti β2GP1. They may be classified as Primary, Secondary or CAPS. Various types of infection, drugs or genetic factors are thought to be triggering mechanism. It is common in young with a female prepondence. It is found in -5% of normal persons. Incidence is high in association of SLE and other autoimmune diseases. It may present as recurrent systemic vascular thrombosis and embolism, pregnancy related complication specially recurrent miscarriage, thrombocytopenia, bleeding diathesis, skin manifestation, cardiac involvement, various neurological complications, psychiatric manifestation, pulmonary and gastrointestinal, ocular, renal complication. Diagnosis depends on history, clinical examination and laboratory investigation which demonstrate aPL antibodies through ELISA (anticardiolipin antibodies) and coagulation based test for Lupus anticoagulant. Thrombocytopenia and antibody against β2GP1 may be detected. There is no cure but treatment is individualized basing on preventing risk factors and ant platelet and anticoagulant therapy.
APS is an incurable autoimmune disease occurring in young. Recurrent thromboembolic episodes involving various organs, recurrent abortion and other manifestations like stroke in young, pulmonary hypertension, unexplained headache, dizziness, memory impairment, cardiac involvement with embolism, dermatological involvement and other neuropsychiatric disorders brings the patient to different clinicians. Basing on proper clinical history the diagnosis is confirmed by demonstrating antibodies like anticadiolipin, lupus anticoagulant and β2GP1. Treatment is symptomatic, prevention of risk factors and individualized use of anticoagulant.
• APS is an autoimmune disease due to presence of aPL antibodies like anticardiolipin, lupus anticoagulant and β2GP1.
• Recurrent thromboembolism in young leading to various clinical manifestation are to be kept in mind.
• Recurrent miscarriage in young females one has to think of APS.
• Incidence is high in association of SLE and other autoimmune diseases.
• Stroke in young or myocardial infarction, renal failure and other systemic complications do occur in young.
• Thrombocytopenia may occur in 50% cases of APS with bleeding manifestations.
• Diagnosed by demonstration of antibodies through ELISA &coagulation based test.
• Though there is no cure for the illness, prevention of risk factors and use of anticoagulants depending on clinical state and symptomatic treatment is useful.

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Tumor markers are biochemical substances usually proteins released by tumor cells either due to cause or effect of malignant process. Some are specific while others are seen in several cancers. Many are also seen in non-cancerous conditions. They may be intracellular seen in tissues or released into circulation. Search for suitable markers in serum, tissues or body fluids during neoplastic process is of clinical value. Though an ideal marker should be highly sensitive, specific, reliable with high prognostic value and correlate with staging none of the markers identified so far has all the features. However they are helpful to monitor in risk groups, diagnose the probable source, staging the cancer, determine prognosis, guide & monitor treatment and detect recurrence.

CLASSIFICATION :- Broadly they may be classified as :-
1. Oncofetal antigens:-α-fetoprotein(AFP), carcinoembryonic antigen (CEA), pancreatic oncofetal antigen, fetal sulfoglycoprotein etc.
2. Tumor associated antigen/Cancer antigen e.g. CA-125,CA-19-9,CA 50 etc.
3. Hormones e.g. β human chorionic gonadotrophin, calcitonin, placental lactogen etc.
4. Hormone receptors e.g. estrogen & progesterone receptors.
5. Enzymes and isoenzymes e.g.-PSA(prostate specific antigen),PAP(prostatic acid phospatase),NSE(neuron specific enolase),TDT(terminal deoxy nucleotidyl transferase ),PALP(placental alkaline phospatase), lysozymes, alpha amylase etc.
6. Serum&tissueproteins-β2microglobulin,monoclonalimmunoglobulin/paraproteins, GFAP(glial fibrillary acid protein), proteinS-100, ferritin, fibrinogen degradation products etc.
7. Other biomolecules e.g. polyamines.
Some are commonly in use while others are less common.
IDEAL TUMOUR MARKER An ideal tumor marker should have---
1. Highly sensitive and less false negative.
2. Highly specific and less false positive.
3. Should have high +ve &-ve predictive value.
4. 100% accuracy in differentiating healthy & cancer patients.
5. Differentiate between neoplastic & non-neoplastic conditions showing +ve correlation with tumor volume and extent.
6. Predict early recurrence and have prognostic value.
7 . Clinically sensitive to detect in early stage.
8. Level should precede neoplastic process to screen early.
9. Should be universal to all or specific to one malignancy.
10. Easily assayable , able to indicate all changes during treatment.

1.Alpha fetoprotein(AFP)— It is a major fetal serum globulin with a molecular weight of 65000. In fully matured fetus the AFP gene is completely repressed leading to its disappearance soon after birth. Though abundant in fetal blood, in normal adult the value is 15ng/ml. A value of serum AFP >500ng/ml indicate malignancy besides pregnancy. During fetal life AFP is synthesized in liver (main), yolk sac and GI tract. Fetal liver produce AFP about 30mg/day. In first trimester amniotic fluid contain yolksac derived AFP (Concanavalin-A non reactive). Later increased portion of AFP is liver derived(Concanavalin-A reactive). AFP reaches a peak between 30-32 weeks of pregnancy and decline suddenly before term. Clinical significance of AFP level is of value in prenatal diagnosis of open spina bifida, anencephaly, atresia of esophagus and multiple pregnancy.AFP level also aid in diagnosis,prognosis and monitoring primary hepatocellular carcinoma, hepatoblastoma, non seminomatous testicular germ cell tumors like embryonal carcinoma, teratoma, choriocarcinoma, yolksac carcinoma, germ cell tumors of ovary and extragonadal germ cell tumors. Most well differential and highly anaplastic hepatomas do not produce AFP, as AFP synthesis is associated with degree of liver cell differentiation. Significant rise of AFP is rarely seen in malignancy of GIT, pancreas, lungs, kidney and breast etc. Moderate rise of AFP is seen in viral hepatitis, chemical hepatic injury, hepatic necrosis, liver surgery. AFP < 400ng/ml is seen in 10-15% cases of acute and chronic hepatitis, cirrhosis, secondary malignancies. Serial AFP estimation shows steady and progressive rise in malignancies in contrast to fluctuation in nonmalignant condition. Pure seminomas are nonsecretor of AFP whereas in nonseminomatous germ cell tumors the AFP indicate progress, monitor treatment and recurrence. Dysgerminomas are AFP nonsecretors while highly malignant endodermal sinus tumours show raised AFP. Measurement of serum AFP is helpful in diagnosis, prognosis, and monitoring efficiency of chemotherapy, radiotherapy, surgery and recurrence of all malignancies discussed. Yolk sac and liver AFP synthesized during fetal and adult life are immunologically cross reactive but different. Because of their affinity to lectin AFP can be resolved to concannavalin A reactive(R con A) and non-reactive (NR con A) fraction. Quantitive as well as qualitative evaluation of AFP vaiant reveal two types, one specific to liver and other to yolk sac.

2.Human chorionic gonadotrophin(βHCG):- HCG, A marker of germ cell tumors and trophoblastic disease, is 45KD glycoprotein, composed of two dissimilar subunits the αchain(14 KD) and βchain(24 KD). It contains 30% carbohydrate. The beta subunit determines the immunological and hormone specificity. HCG is synthesized by the synctiotrophoblasts of the placenta during pregnancy. The peak HCG concentration is reached between 10th & 12th weeks of gestation. The reference values in serum of healthy men and non-pregnant women are less than 5 IU/ml and post-menopausal women are less than 10IU/ml. HCG is a marker of first choice for gonadal (testes and ovary) choriocarcioma. HCG shows 100% sensitivity for choriocarinoma irrespective of their site in addition to hydatidiform mole. In testicular tumors, the detection of βHCG and AFP correlate with the histological findings and is therefore crucial for the therapeutic procedures with the use of serial determination of βHCG. The biochemical recurrence precedes by 3 months before the patient has symptoms of clinical recurrence/metastasis. The marker also helps in monitoring high-risk group of testicular tumors especially individual with undescended testicle or the healthy monozygotic twin of a testicular tumor patient. High levels of βHCG indicate poor prognosis and frequent assays during therapy level correlate to the clinical response. Serum βHCG levels are rarely elevated in nontrophoblastic tumors such as lung, breast, pancreas and bladder cancers.

3.BETA-2Microglobulin(β2M):- β2M is 11 KD light chain constituent of HLA antigen. The β2M is used clinically as a marker of first choice for B-cell leukemia, lymphomas and multiple myeloma. However, due to its non-specificity its moderate elevation is observed in cases of solid tumors and also in various inflammatory diseases, benign infectious disorders, and primary billiary cirrhosis and in acquired immune deficiency syndrome. It is used routinely for evaluating tumor cell load, disease activity and prognosis. It is also used to monitor efficacy of patient’s response to treatment. Elevated levels of β2M are also reported in cerebrospinal fluid (CSF),in CNS metastasis, acute lymphoblastic leukemia. lymphoma and other lymphoproliferative disorders/diseases. Hence the determination of β2M in CSF helps in identifying and managing CNS metastases. Serum β2M could be clinically relevant marker for Waldenstrom’s macroglobulinemia, secretary and non-secretary multiple myeloma, leukemia and lymphoma. Like other tumor markers, β2M has proven to be the best marker for monitoring therapeutic courses, as it useful serum parameter to monitor tumor progression as well as early biochemical relapse. Serum β2M is the most powerful prognostic marker of monoclonal gammapathies.

4. BRCA 1 &BRCA 2:- BRCA 1and BRCA 2 belong to few tumor suppressor susceptibility genes having high risk to few cancers.BRCA1 predicts high risk for breast, ovary, colon and prostate cancers. BRCA2 gene mutation is seen in 70% of breast cancers in women and men. More than 100 germ line mutations are reported in BRCA gene applying current molecular technology.

5.BTA(Bladder tumor antigen):- Not widely used. Urine level helps in diagnosis and recurrence of bladder tumors. May be raised in kidney stones and urinary tract infection.

6.Carcino-embryonic antigen(CEA): -CEA, is a glycoprotein of 200 KD. Radioimmunoassay (RIA) made it possible to detect very low concentrations of CEA in blood, other body fluids, and also in normal and diseased tissues. It is excreted by certain embryonic and adult tissues in addition to adenocarcinoma of the digestive organs. Extensive studies of patients bearing primary and metastatic colorectal neoplasms have determined that its primary use is in the detection of local and metastatic cancer recurrence after initial resection of the primary tumor, through periodic postoperative analysis of CEA in serum or plasma. The notion that fluids bathing tumors in metastatic sites might contain higher levels of CEA than those found in the blood led to analysis of CEA levels in gallbladder bile from patients bearing colorectal liver metastases. It was observed that CEA levels in gallbladder bile were strikingly higher than those in serum. Furthermore , linear regression analysis of tumor volume versus gallbladder bile CEA levels in patient with liver metastases predicted that tumors as small as 1 cm would produce easily measurable gallbladder bile CEA levels as high as 41ng/ml. This data suggested that measuring biliary CEA levels in patients with primary colorectal lesions might permit detection of small, occult colorectal liver metastasis earlier than now is possible through conventional methods (computed tomography liver scanning, ultrasound, and intraoperative exploration). The results of clinical studies that CEA, although originally thought to be specific for digestive tract cancers, may be elevated in other malignancies and in some nonmalignant disorders. CEA testing is of significant value in the monitoring of patients with diagnosed malignancies in whom changing concentrations of CEA are observed. A persistent elevation in circulating CEA following treatment is strongly indicative of occult metastatic and / or residual disease. A persistently rising CEA value may be associated with progressive malignant disease and a poor therapeutic response. A declining CEA value is generally indicative of a favorable prognosis and a good response to treatment. Clinical relevance of the CEA assay has been shown in the follow-up management of patients with colorectal, breast, lung, prostatic, pancreatic and ovarian carcinoma. CEA testing recommended as a screening procedure to detect cancer in the general population; however, use of the CEA test as an adjunctive test in predicting prognosis and as an aid in the management of cancer patients has been widely accepted.

7.Cancer antigen 125(CA 125):- It is a glycoprotein of more than 200 KD, detected by monoclonal antibody. Healthy women has < 35 U/ml in their serum. It is a first marker of choice in epithelial ovarian carcinoma specially adenocarcinoma (high sensitivity 80% specificity 96%). It is useful for staging, prognosis& recurrence. It may be raised in malignancies of breast, colorectal, gastric, esophagus, liver, billiary tract, pancreas, lungs, and endometrium. After removal of ovarian tumor there is rapid decline within a week and normalize within 3-4 weeks. CA-125 value indicates prognosis, remission or relapse. Nonspecific mild rise may be seen in begin ovarian cyst.(follicular cyst), endometriosis, coelomic epithelium pathologies, cirrhosis, pleural effusion, ascites, peritonitis, pericarditis, during menstruation and last trimester of pregnancy.

8. Cancer Antigen 19-9:- It is a marker of first choice in cancer of pancreas and gall bladder. It is 210 KD glycoprotein antigen having carbohydrate on glycolipid and glycoprotein, detected by monoclonal antibody assay. The antigen is located immunologically in fetal epithelium of colon, small intestine, stomach, pancreas, liver, adult GIT and lung. Appreciable level is seen in mucin rich saliva, seminal fluid, gastric juice, amniotic fluid, urine, ovarian cyst fluid, pancreatic, gallbladder and duodenal secretion. Normal value is < 37U/ml and < 100U/ml is considered as grey zone where malignant and benign disease may overlap. In malignancy value may be > 100,000 U/L. In pancreatic tumor (sensitivity -85%, specificity -95%), cholangiocarcinoma and gall bladder carcinoma ( sensitivity 70%) it is helpful. It may have low sensitivity in colorectal, stomach, primary liver, bronchial, mucinous ovarian, uterus and mammary carcinoma. Besides diagnosis its value predicts recurrence after pancreatectomy. Nonspecific rise may occur after acute or chronic pancreatitis. (8%).

9.CA15-3:- Ca 15-3 is heterogeneous 300 KD glycoprotein antigen. The diagnostic sensitivity of the CA 15-3 for breast carcinoma is low as its elevated level is also observed in benign breast diseases and cirrhosis, acute and chronic hepatitis and in metastatic cancers of pancreas, ovary, colorectal, lung, stomach, uterus.

10.CA72-4:- Its molecular weight is more than 106 KD. This antigen was detected in fetal epithelium and also in serum of patients of various adenocarcinoas. CA 72-4 once emerged as the marker of first choice for gastric carcinoma and is thereby superior to CA19-9 and CEA. The sensitivity of CA 72-4 was found to be 38%. CA 72-4 is considered to be the multiple marker for epithelial cell derived tumors.

11.CA 19-5 & CA-50:- CA 19-5 was found to be associated with colon, pancreatic and hepatocellular carcinoma. Individually both antigens have low sensitivity. However use of both together improves sensitivity in detecting pancreatic and other carcinomas.

12.CA 549:- CA 549 is a high molecular weight circulating glycoprotein antigen associated with breast cancer. Elevated level of CA 549 is observed in serum of advanced breast cancer by using sensitive immunoassay. However, it has very low sensitivity; very low negative predictive value and high positive predict value for early breast cancer.

13.Cytokeratins/Keratins:- Keratins are remarkably diverse, highly resistant and the most conserved cytoskeletal proteins are present in all types of epithelial cells. The composition of keratin filaments ranges from a few polypeptides to 19 different polypeptides ranging from 40 to 68 KD. Keratins have gained importance as marker protein in diagnosis of tumor of epithelial origin. There may be variation in keratin expression compared to normal tissue, depending on degree of differentiation of epithelial tumors. This property of keratin allows their use in combination with other changes as markers for malignant transformation in epithelioid tumors. Keratins has 2 main applications(i)distinguish epithelial from non epithelial tumors and(ii)distinguish type of epithelial tumor. Keratin is reliable marker of (i)undifferentiated and anaplastic carcinoma(ii)infiltrating carcinoma(iii)metastasizing single carcinoma cell in suspension. It may be used for epithelial carcinomas, especially those of stratified and sqamous cell origin e.g. lung , breast, urinary bladder, thymomas and cervical carcinoma. As GItract lining from buccal mucosa to rectum including pancreas and gall bladder is of epithelial origin keratin may serve as an useful marker. Keratin has been used as a differential marker in thyroid, GItract, prostate, lung and breast.

14.Cyfra 21-1:- It is used as a marker for non small cell lung cancer (NSCLC),squamous cell carcinoma(SCC), adenocarcinoma and large cell carcinoma. This marker has highest sensitivity for SCC in lung. Both Cyfra 21-1 and CA19-9 have improved detection of adenocarcinoma of lung.
15.Calcitonin:- Calcitonin a low molecular weight peptide hormone secreted from C cells of thyroid is used as a marker, as increased level is seen in malignancies with skeletal metastasis. It is increased in medullary carcinoma of thyroid, bronchogenic carcinoma, small cell cancer of lung, breast, liver, lung, renal and carcinoid tumors.

16.Catecholamines:- Plasma and urinary epinephrine and norepinephrine are raised in Pheochromocytoma.

17.CathepsinD:- Lysosomal aspartyl protease of lysosomes is considered a potential marker for breast cancer metastasis. Cathepsin D predicts early recurrence. It has high prognostic value in node-ve breast cancer than node+ve breast cancer. Patients with low Cathepsin D value have better survival. High level of Cathepsin D enhances metastasis in breast cancer.

18.Chromogranin A:- Chromogranin A(secretogranin 1) belongs to group of closely related secretary acid protein is used as a marker to asses exocytotic sympathoadrenal activity in Pheochromocytoma. In peptide producing tumors it is raised.

19. CA27.29&CA 15-3:- Usually seen in breast cancers. May be +ve in colonic, gastric, hepatic, lung, ovarian, prostatic cancers and breast, liver, kidney diseases and ovarian cyst.

20. Circulating methylated DNA:- Circulating nucleic acids may be used as marker in early detection, follow progression. DNA is a stable molecule and detected by PCR.

21.Epidermal growth factor receptor(EGFR): -EGFR a 170 KD glycoprotein binds to epidermal growth factor(EGF). It is raised in breast cancer, gliomas, lung cancer, SCC and tumors of female genital tract. Absence of EGFR indicates a good response to Tamoxifan therapy.

22.Estrogen receptor(ER),Progesterone receptor(PR):- ER a 70 KD protein is present in mammary and uterine tissues. ER &PR belongs to receptor super gene family including receptors for thyroid hormone, vitamin D3 and retinoic acid. In breast tumor their level indicate benefit of hormone therapy. 55% to60% ER positive primary breast cancer show good hormone response. Following mastectomy high PR&ER positive tumors have longer survival. PR is more sensitive than ER.

23.Ferritin:- Serum ferritin an acute phase reactant is an intracellular protein playing a role in sequestration and storage of iron. Increased ferritin level is seen in cancers in absence of iron overload. It is increased in advanced breast, ovary, lung, colon, esophagus cancer, acute myelocytic leukemia, teratoblastoma and SCC of head and neck.

24.Homovanillic acid(HVA) & Vanillymandelic acid(VMA): -HVA &VMA are acid metabolites of catecholamines. Their increased excretion is observed in neural crest tumors. They also help in detecting and monitoring therapy in Pheochromocytoma & Neuroblastoma.

25.Hydroxy indole acetic acid (5-HIAA):- Urinary measurement helps in indole secreting tumors. Helps in diagnosis and therapy monitoring in Carcinoid tumors.

26.Her-2/neu(also known as HER,erbB-2,EGFR-2):- Seen in 20-30% of advanced breast cancers. It determine prognosis and guide treatment.
27. Human telomerase reverse transcriptase (hTERT):- It is a novel and newly available biomarker for patients with ovarian and uterine cancers. The hTERT mRNA level has a significant correlation with CA-125 and with histological finding in ovarian cancer. Serum hTERT mRNA is useful for diagnosing gynecological cancer and is superior to conventional tumor markers. Up regulation of hTERT may play an important role in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. So hTERT could be used as an early diagnostic biomarker for cervical cancer in future.

28.Interleukin-2 receptor/Tac antigen(IL-2R):- IL-2 α a 55KD glycosylated protein is seen in some types of lymphoid malignancies like T-cell leukemia. It my monitor treatment.
29. Inhibin:- Inhibin is a peptide hormone normally produced by ovarian granulosa cells. It inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. It reaches a peak of 772 +/-38 U/L in the follicular phase of the menstrual cycle and is normally undetectable in the serum of menopausal women. Granulosa-cell tumors produce inhibin and its serum levels reflects the tumor burden. Measurement of inhibin can be used as a marker for primary as well as recurrent granulosa cell tumor.The recent availability of markers of ovarian stroma, including melan-A and inhibin- alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest in a myriad of histological appearances.The hormonal activity of granulosa cell tumors permits the use of a variety of serum markers in the diagnostic evaluation. Clinically the most useful serum marker for granulosa cell tumors is inhibin. Inhibin exists in 2 different isoforms. Inhibin-A and Inhibin-B. Both isoforms consists of a dimmer of 2 subunits, the alpha and beta subunits. Inhibin usually becomes no detectable after menopause. However, certain ovarian tumors mostly mucinous epithelial ovarian carcinoma and granulosa cell tumors produce inhibin. An elevated level in a postmenopausal women or a premenopausal women presenting with amenorrhea and infertility is suggestive of the presence of a granulosa cell tumor, but not specific. Inhibin levels can also be used for tumor surveillance after treatment to assess for residual or recurrent disease.

30.Lipid associated sialic acid in plasma(LASA-P):- Increased level is seen in malignancies of breast, GItract, lung, leukemia, lymphoma, Hodgkin’s and melanoma(sensitivity vary -77% to97%). Slight increase is seen in many inflammatory diseases indicating poor specificity.
31. Lysophospatidic acid:- It stimulates cancer cell proliferation, intracellular calcium rise and tyrosine phosporylation. It is found in ascitic fluid of ovarian cancer.

32.L1(CAM):- It correlates with stage and grade of ovarian cancer and response to chemotherapy.

33.LDH(lactate dehydrogenase):- Though one of the first marker clinically used may be raised in many cancers. It is currently used in monitoring some leukemias and lymphomas.

34.Monoclonal immunoglobulin/Paraprotein:- Monoclonal immunoglobulin content is of value in diagnosis and monitoring management of plasma cell tumors like Multiple myeloma, Waldenstrom’s macroglobulinemia, plasma cytoma, B cell leukemias and lymphomas.

35.Mitf (Microphthalmia transcription factor):- It is important in melanocyte development and growth. It is tried in determining disease stage and survival, detect sub clinical metastasis and outcome of treatment.

36.Mullerian inhibiting substance(MIS):- MIS is produced by granulosa cells in the developing follicles. It has emerged as potential tumor marker for granulosa cell tumors. As with inhibin, MIS is typically undectable in postmenopausal women. The elevated MIS level is highly specific for ovarian granulosa cell tumors. However, this test is not commercially available for clinical use.

37.Neuron specific enolase(NSE):- NSE, the gamma subunit of enolase enzyme is present in neurons & neuroendocrine cells.NSE is raised in glucagonoma, insulinomas, carcinoid tumor, pheochromocytoma, medullar carcinoma of thyroid, oat cell carcinoma, small cell and other lung cancers. It is marker of 1st choice in SCLC.NSE monitoring is used in assessing prognosis and therapeutic response in85% of neuroblastoma and SCLC.

38.NMP-22:- Not widely used. Urine level helps in diagnosis and recurrence of bladder tumors(>10 units/ml).

39.Oncogene P21 RAS:- RAS ,one of the transformation inducing gene belonging to family of cellular oncogens(c-ras) frequently seen in human solid tumors like colorectal carcinoma, large adenomas, bladder and lung tumors.

40.Prostate specific antigen(PSA):- PSA known earlier as gammaseminoprotein is 34 KD single chain glycoprotein (93% amino acid, 7% carbohydrate) , a monomer made up of 240 amino acid residue. It is a neutral serine protease, having trypin and chymotrypsin like activities belonging to glandular kalkrein family. Synthesized from prostate epithelium. Small amount of PSA released to circulation form complexes with different protease inhibitors detected in serum and seminal fluid. PSA-ACT complex (major immunoreactive form 80-90%), PSA-AT (α-1 antitrypsin) PSA-PCI(protease C inhibitor ) and PSAα2M(α-2 macroglobulin) are different complexes. The remaining PSA are free immunoreactive form(5-15%). PSA is most useful and clinically relevant marker for prostatic cancer. It is useful for early detection, prevention and assay efficacy of treatment. PSA is synthesized in low quantity by normal prostate, mild quantity in inflamed or hypertrophied prostate, prostatic trauma, after ejaculation and in large quantity by malignant prostate. Due to overlap at times there may be difficulty to distinguish between BPH and early cancer. However combined with digital rectal examination and transrectal ultrasound PSA proves useful in adenocarcinoma besides biopsy. The value of PSA also increases with age and there is correlation between total and free PSA. Indian males have low level as compared to other countries. Though the normal cut off value is 4ng/ml it increases with age. Use of age specific reference value will improve diagnostic efficacy. Clinical analysis of molecular forms of PSA, free PSA, or free PSA/total ratio are useful to differentiate begin from malignant conditions. Other markers in prostatic cancer are PAP, Alkaline phosphates (ALP), PSMA,
Zn-alpha-2-glycoprotein, leucine amino peptidase, lactic dehydrogenase.

41.Prostate acid phospatase(PAP):- Acid phosphates activity is 200 times more abundant in prostate tissue than in any other tissue. Acid phosphatase prostatic fraction is useful only in staging apparently localized disease i.e., primary prostate cancer before definitive therapy such as radical prostatectomy. Its activity in serum can be estimated by several synthetic substrates, but now specific antibodies are available for immunoassay. The enzymatic assay appears superior to the immunoassay in this context. Interest in acid phosphates assay in serum as a measure of prostatic cancer staging has decreased with the availability of more sensitive and specific PSA assay.

42. Parathyroid hormone related peptide(PTH-RP):- Elevated plasma level is seen in cancers having hypercalcemia. It helps to differentiate primary hyperparathyroidism, sarcoidosis, vitamin-D, squamous cell carcinoma of renal, bladder and ovarian cancers.
43.PS 2:- PS2, a low molecular weight cysteine rich protein is raised in 50% of breast tumors. Its expression indicates better prognosis than ER and PR. It is also seen in normal stomach mucosa and ulcerative disease of GItract.

44. PSMA (Prostate specific membrane antigen):- Though not used, may rise with age and serum level indicate prostate disease.

45. S-100:- Though not widely used, may help in diagnosis of metastatic melanomas.

46.Tissue polypeptide antigen(TPA):- TPA regarded as a marker of cell proliferation, is a mixture of proteolytic fragments cytokeratins 8,18,and19. These fragments are released during necrosis and lysis of cancer cells. TPA is regarded as a broad spectrum epithelial marker. Moderate elevation occurs in many diseases and pregnancy. Marked elevation is reported in cancers of breast, lung, gastrointestinal, urological and gynecological conditions.TPA though sensitive but not specific. TPA with CEA help in monitoring lung, breast, bladder, colorectal and ovarian carcinomas.

47. Tumor suppressor gene P53:- P53, a 53 KD nuclear phospoprotein acts as tumor suppressor by inhibiting cell proliferation and plays a role in cellular apoptosis.P 53 gene mutation seen in 50% of all cancers like breast, colon, ovary, lung and esophagus.

48.Squamous cell carcinoma(SCC) antigen:- SCC antigen, a 48KD protein is purified from uterine cervix. It is raised in squamous cell cancer of head & neck, lung, esophagus and anal canal. Highest level is found in metastasis. It is elevated in advanced cervical cancer, determine progression or regression following chemotherapy. Combined use of CEA, NSE, SCC antigen increase sensitivity in detection and monitoring lung cancers.

49. Thyroglobulin:- Used after removal of thyroid to find recurrence. It is elevated in many thyroid diseases. In some antibody is formed against thyroglobulin. So level of antithyroglobulin antibody is measured at the same time.

50. Topoisomerase II:- Topoisomerase II expression is detected in tumor samples by immunohistochemistry and has emerged as a promising, clinically relevant biomarker for survival in patients with advanced epithelial ovarian cancer.

51. TA-90:- Recently on trial to diagnose metastatic melanomas. This protein is found on outer surface of melanoma cells. Its use is studied in colon and breast cancer.

52. Other Gynecological markers:- Other markers in many gynecological conditions are-
Urinary gonadotrophin fragment, Tumor associated trypsin inhibitor, Cyclin E, Mesothelin, HE4, Osteopontin, Ineterleukin 8, Vascular endothelial growth factor(VEGF), Macrophage colony stimulating factor, Insulin like growth factor-binding protein-3, OVX, NB70/K, HMFGR (human milk fat globule)

METHODS:- Common methods used to identify tumor proteins are-
1. Immunohistochemistry- Traditionally most methods have used monoclonal antibodies and immunohistochemistry. They can be used directly in tumors or serum, bonemarrow, lymphnodes.
2. Reversed transcriptase and polymerase chain reaction(RT-PCR)

USEFULNESS:- Tumor markers are usually used for--
1. Detection-Screening in asymptomatic cases for early diagnosis.
2. Diagnosis-Differentiating malignant from benign condition.
3. Monitor-Predict effect of therapy and detect recurrence.
4. Prognosis-Choosing therapy and predict tumor behavior.
5. Therapy-Directing cytotoxic agents to marker containing cells.

Tumor markers are biomolecules released or formed during neoplastic process. Though an ideal marker is yet to be identified they aid in detection, diagnosis, monitor response and recurrence. They may be raised in some nonmalignant conditions.
In urinary bladder tumor BTA and NMP-22 are used along with urine cytology and cystoscopy. In advanced cancers CEA, CA-125,CA 19-9 & TPA are raised.
In breast cancers ER,PR and HER/neu are used for diagnosis. In advanced cases follow-up and recurrence are detected by CA15-3, CA 27-29 & CEA.
In colorectal advanced cancers CEA & ca19-9 are elevated, but neither is helpful for screening test. They are used for follow-up and recurrence.
Gestational trophoblastic diseases show elevated βHCG.
In liver cancers AFP is used for screening, diagnosis and follow-up.
In lung cancers no marker is useful for screening. CEA is raised in non small cell cancer and NSE in small cell cancers and used for evaluation of treatment.
Though no marker is useful for screening TA-90, S-100 and other markers help to find metastasis, follow-up and prognosis.
In multiple myeloma immunoglobulins,β2M are helpful.
In ovarian epithelial cancer CA-125 is usually elevated. Others like CA72-4 & LASA-P are raised. In ovarian germ cell tumor βHCG and AFP are raised.
In pancreatic cancer though no marker is helpful for screening CA 19-9 & CEA are used.
For prostatic malignancy PSA is commonly used. Markers like PSMA, chromogranin-A and PAP are also useful.
Though no marker has developed for stomach cancer CEA,CA 72-4 & 19-9 are raised at times.
For testicular tumor βHCG is elevated in seminomas where as AFP or βHCG or both are raised in nonseminomas.

Though all tumor marker are not ideal biomarkers their judicious use following evidence based medicine are clinically helpful. Inspite of nonspecificity of wide spectrum of available markers, their potential role in monitoring entire cancer therapeutic course is clinically relevant.

 Tumor markers are substances which indicate probable presence of malignancies.
 Few are specific, most of them are nonspecific. Many are seen in nonmalignant conditions.
 All of them are classified into various biochemical groups.
 Though tried since long not a single one fulfill the criteria of ideal marker.
 AFP is specific for liver cancers.
 BTA,NMP-22,CEA,CA125,CA19-9, TPA indicate bladder cancer.
 TA-90,S-100 indicate melanoma.
 ER,PR,HER/neu,CA15-3,CA27-29, CEA are indicative of breast cancers.
 PSA,PSMA,PAP are raised in prostatic conditions.
 CEA,CA72-4,CA19-9 are raised in gastric malignancies.
 CEA,CA 19-9 are increased in pancreatic and colorectal cancers.
 CEA,NSE are raised in lung cancers.
 CA-125,βHCG and AFP are raised in ovarian conditions.
 In testicular tumors βHCG &AFP are raised.
 They are detected by immune assay or RT-PCR.
 Few are used for screening asymptomatic cases while others are helpful for diagnosis, staging, prognosis, response to resection or chemotherapy and recurrence.

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Malaria is the most important of the parasitic diseases of humans with transmission in more than 100 countries, affecting more than 1 billion people and causing 1- 3 million deaths each year. It is a major cause of morbidity and mortality in tropical regions. Plasmodiurn falciparum infection is a prime cause of concern in India where a resurgence of infection is being witnessed in the present decade. The state for Orissa with a population of 4% that of India, accounts for 25% of all cases of malaria .Orissa also bears the highest mortality rate of 35% of total malaria deaths in the country. Cerebral malaria is the most dreaded form of malaria, carrying a mortality rate of 50% even in treated patients. The SPR (Slide positivity rate) in Orissa is 11.89% of which 84% are pl. falciparum and death rate is 35% of the total mortality in the country. WHO has fixed a goal to reduce malarial mortality by 50% by 2010.
Fever is a common presentation of patients in developing countries like India and most of which are of infectious etiology. Thus malaria is one of the leading causes. The clinical profile of falciparum malaria involves hepatic, renal, circulatory, respiratory and cerebral features . There are several clinical and biochemical parameters, which have been claimed to predict outcome with reasonable degree of accuracy. Among them TNF- α in falciparum malaria mediate different biochemical changes.
In the past, changes in lipid profile have been observed in malaria (Vernes et al, 1980, Nissen - Ehle et al, 1990, Parola P et al 2004). Most of the time it is not possible to ascertain the etiologic agent in a case of pyrexia, as malaria parasites are difficult to be found out in blood . Hence the above mentioned acute phase reactants mediated changes in lipid profile may be considered as an indirect evidence of infection by different etiologic agents. As it is difficult and costlier affair to measure TNF - α and other acute phase reactants and lipid profile measurement is a cheap and widely available alternative, its estimation may be useful in diagnosing, differentiating or predicting outcomes in malaria.

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Sickle cell Disease was first described by James B. Herrick in November 1910. Since its first record, it has been detected in many part of the world including Orissa.
Sickle Cell Disease is a chronic inherited disease transmitted as Mendelian recessive character. It is a disease of hemoglobin structure where the glutamic acid in the 6th position of Beta Chain is replaced by valine. This disease may be present either in homozygous state or in conjunction with other type of normal or abnormal haemoglobin. The clinically significant sickle cell haemoglobinopathy include Sickle Cell Trait, Sickle Cell Disease, Sickle Beta thalassemia, Sickle Cell ‘C' Disease, Sickle Cell ‘D’ disease and Sickle ‘0’ Arab disease etc. These may present with different clinical severity ranging from mild symptoms to fatal complications. They usually present as chronic haemolysis, Sickle Cell crisis, growth retardation, increased susceptibility for infection and variety of other acute and chronic, complications that produce multi system organ damage, disability and death. Their clinical severity depends upon presence of precipitating factors or association with other abnormal or normal haemoglobin variants.
The most important clinical presentation is Sickle Cell crisis. The Sickle Cell Crisis was defined by Diggs L.W. in 1965 as “a sharp turn on the course of the disease with rapid development of new symptoms not explained by any other cause". There are four types of crises, such as vaso-occlusive crisis, Aplastic crisis, Haemolytic crisis and Sequestration crisis. The Vaso-occulusive crisis is the commonest and is very painful. The Vaso-occlusive crisis is defined as sudden onset of excruciating pain in different parts of the body particularly extremities, chest, abdomen etc. due to occlusion of microcirculation by the sickled erythrocytes. The crises are precipitated by many factors like anoxia, infection, acidosis, dehydration, exposure to cold, pregnancy, emotional stress etc.
Despite substantial increase in knowledge in cellular, in pathological and physical basis of sickling phenomenon, there is some therapy available for prevention of crisis. There is some hope in gene replacement therapy and bone marrow transplantation in future and cure of the disease.
Currently accepted management of painful crisis includes.
1. Prophylactic measures to reduce the incidence or crisis and
2. Therapy to relieve- or reverse the established crisis by
a) Early detection and prompt management of precipitating factor- infection should be treated with suitable antibiotic, hypoxaemia with oxygen, acidosis with alkali and dehydration with adequate IV fluid.
b) Analgesics for control of pain
c) Stabilization of Red Blood Cell membrane
d) Vasodilatation to improve microcirculation
Many drugs like phenothiazine, Nitrates, Urea, Nicotinic acid, Dextran, alkali, Androgen, Aspirin, Desmopressin acetate, 5 azacytidine etc. have been tried with partial or no benefit and none of them are also safe. New compounds continue to be sought, that might interfere with sickling and be useful clinically. Aspartame is the only agent that can prevent sickling and reverse sickling tested in-vitro and in-vivo so far (Manion et al, 2001). Therefore this study is undertaken to know the efficacy of drug (Aspartame) in sickle cell disease and sickle cell crisis.
A glucose analogue aspartame (L. aspartyl L. Phenylalanine) a sweetener prepared from 2 amino acids -  - aspartic acid and L-phenylalanine is appears to be beneficial effects in sickle cell disease and sickle cell crisis. This drug can prevent fibril formation and / or interaction with or by getting inserted into the EF acceptor site and prevent the  - helix that contain valine  from its delectation binding to the EF acceptor site and thus obstruct sickling. A possibility of functional interaction of intracellular biopolymerization may occur appears to be possible mechanism (Manion et al, 2001).

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The thyroid is one of the important endocrine glands in human being. It secretes hormones like thyroxine (T4), tri –iodothyroine (T3) and calcitonin. The relationship between the thyroid gland and various body functions was studied in 1827 (Werner & Ingbar). Perry in 1835 described the clinical manifestation of exophthalmic goiter. Its association with angina pectoris and congestive heart failure.
In peripheral tissues,T4 in mainly metabolized to form active hormone 3,5,3’ – triiodothyronine (T3) and inactive 3,3’,5’,- triiodothyronine (reverse T3) as per the demand of the body (Bitman et al, 1971 and Chopra et al 1978). Non – thyroidal acute and chronic illnesses are the major cause of disordered peripheral thyroid hormone metabolism often poses a major problem in interpreting thyroid function tests (Cavalieri and Repport. 1971) it is generally agreed that despite gross abnormality in circulating thyroid hormones, most of these ill patients are clinically euthyroid.
A wide variety of systemic illnesses like infarction. malignant disease, hepato –cellular failure, renal failure protein – calorie malnutrition, congestive heart failure are associated with decreased T3, elevated reverse T3(rT3) and decreased, normal or increased serum T4 concentration. (Burger et al 1976, Rosenthal and Cavelieri, 1979).
AMI, frequently fatal form of ischemic heart disease (IHD) results due to considerable jeopardisation of coronary blood flow, is one of the commonest systemic nonthyroidal illnesses where thyroid hormone economy in altered. But conflicting reports regarding thyroid status has been published in this condition. Supra normal value of T4 in AMI have been observed by Wierainga et al 1981, Vanhaelst et al 1976 and Kirkeby et al 1984.
On the other hand decreased T3 and T4 in face of elevated reverse T3 has been observed by Kaplan 1977, Westgreen et al 1977 and Marek et al 1980.
Normal T4 with unequivocal elevation of rT3 and significant reduction of T3 also have been found by Smith et al 1978, Fabre et al 1980 and Lada et al 1981.
It has been also observed that magnitude of lowering of T3 and T4 correlates well with the severity of illnesses and survival. (Larty et al 1975 and Kaptain et al 1978, 1982)
The outcome of AMI depends of many factor like degree of myocardial damage, associated arrythmias, hypotension and shock.(Hurst 1982). How ever, commonly sudden death occurs in those cases with or without complication.
It is the intended:-
1. To study the thyroid hormone levels in AMI through out the illness.
2. To correlate the changes of thyroid hormone levels with the severity of these conditions.
3. To correlate the thyroid hormone levels with outcome that is recovery or death.
The thyroid is the largest endocrine gland. In the past it escaped the notice of most of the investigators owing to its inconspicuous shape and position. Vasalius in 1543 described it in details while Whartsen in 1656 named the organ “The Thyroid”
The relationship between the thyroid gland and various body function was studied in 1827. Parry in 1835 described the clinical manifestations of exophthalmic goiter and its associations with angina pectoris and congestive heart failure. In 1915 Kendall found the L – thyroxine (T4) from thyroid tissue whereas Pitterson and Gross found tri – iodothyronine in plasma and thyroid in 1954. ( Werner and lngbars H.,1971). Several studies have shown the relationship of the thyroid hormones with the thyroid and non thyroidal illnesses ( Herrison, Mc Donald, Hoffman, and Pool). Levy in 1971 demonstrated increased adrenergic activities in hyperthyroidism.
The Thyroid is highly vascular and comprises the follicles which contain proteinacious colloid. The colloid contains glycoprotein, thyroglobulin (TG) within which thyroxine(T4) and Tri – iodothyronine (T3) are formed and stored. Moreover, thyroid contains parafollicular cells which secrets calcitonim. (Copp & Co- workers in 1962).

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Pseudoxanthoma elasticum is a rare inherited disorder of connective tissue, characterized by general elastorrhexis of the elastic tissue in the dermis, the blood vessels and Bruch membranes of the eye.

Pseudoxanthoma elasticum (PXE), Angioid streaks, Bruch’s membrane, Connective tissue, Haematuria.

A 55 years Hindu female presented with complain of recurrent haematuria for 6 months, diminished vision for one year and weakness of left half of the body since 3 years. She had attended menopause and was under Enalapril (5 mg) since 1 year for hypertension. No history of diabetes, tuberculosis or CAD. No suggestive family history.

On examination the patient was of average built with BP 130/80mmHg (both upper limbs) , pulse rate 80/min, regular (Brachial) good volume while diminished pulsation of both radial, ulnar, posterior tibial and dorsalispedis arteries. Both carotids, axillary, femoral and popliteal artery pulsations were well felt. She was mild anaemic without icterus, cyanosis, clubbing or lymphadenopathy. JVP was not raised. Thyroid was normal. Chest examination revealed vesicular breath sounds without any added sounds. Cardiovascular system examination revealed normal apex with normal heart sounds, without any murmur. P/A examination was normal without any renal brui. On CNS examination the cranial nerves, motor, sensory systems were normal without any cerebellar signs or meningeal signs. On examination of the skin, there were laxed skin with yellowish Xanthomatous lesions over neck and upper chest (Fig. 1, 2). Eye examination revealed vision 6/9 (Lt) and 6/6(Rt) and fundoscopy showed macular choroiditis with angioid streaks on left side (Fig. 3).
Routine Investigation Showed: FBS - 82mg%, PPBS – 104mg%, Blood Urea 20 mg%, Serum Creatinine 1.08mg%, ESR - 20mm/1 hour, DC N72, L25, E3, M0, B0, and TLC - 8000/mm3, Lipid Profile of serum were Sr. Total cholesterol -160mg%, TGS -108mg%, HDLC -48mg%, LDLC- 92mg% and VLDL-C -21mg%, Urine analysis showed proteinuria(+) and 10-15 RBC/HPF and RBC casts. Mantoux test was 18mm , ECG was normal.

ECHO Showed: Mitral value thickened, EF – 65%, Aorta – 32 mm, MACS – 17 mm, LA – 42mm.

Skin Biopsy Revealed: Epidermis was normal and dermis showing accumulation of basophilic mucoid material and collagen bundles. There was occasional macrophages and multinucleated giant cells compatible with pseudoxanthoma elasticum.

Colour Doppler study of kidney and renal arteries showed normal kidney size , shape, echo structure and punctate calcific areas on both renal cortex. Both renal arteries and interlobar arteries and aorta showed normal Doppler profile.

Doppler study of upper and lower limb arteries showed:-

Upper Limb: B/L subclavian , axillary, brachial , radial , ulnar arteries were anechoic with normal caliber and showing loss of normal triphasic blood flow with low resistance blood flow in them.
Lower limb: B/L femoral , popliteal and dorsalis pedis arteries were normal caliber with speaks of arterial calcifications seen in arterial wall at places and with loss of normal triphasic blood flow with low resistance.
Aorta and iliac arteries: Showed normal in caliber and size with normal spectrum of blood flow and no thrombus or stenosis. The patients was diagnosed to be a case of Pseudoxanthoma Elasticum with complications leading to peripheral vascular , renal and retinal involvement.

Treatment given: Capsule E, Tab Pentoxyphyllin and advised diet restriction , regular follow up.

Pseudoxanthoma elasticum is a rare disease occurring in about 1 in every 160,000 population. Females are frequently affected. The basic defect lies in the elastic tissue. Typically it is first noticed during adolescence as yellow orange bumps on the side of neck. This entity has been observed in India and has been reported sporadically from all regions.

Pseudoxanthoma elasticum is caused by genetic mutations that are inherited in either a dominant or recessive mode. A person with recessive form of the disease (most common) must posses two copies of the PXE gene to be affected, and therefore must have received one from each parent. In dominant form , one copy of the defective gene is sufficient to cause the disease. In some cases, a person with dominant form inherits abnormal gene from a parent with PXE, more commonly, the mutation , arise as a spontaneous change in the genetic material of the affected person. These cases are called “ Sporadic” and do not affect parents or sublings , although each child of a person with sporadic PXE has a 50% risk to inherit the condition.

Actual genetic defect is caused by different mutations or deletion in a single gene called ABCC-6 (also known as MRP6) located on chromosome 16. Although responsible gene has been identified, how it causes PXE is still unknown1.

It has been suggested that defects on glycosaminoglycans or proteoglycans might play a role in pathogenesis, bends of chondroitin sulphate, dermatan sulphate and hyaluronic acid are increased in the areas of calcification2.

An abnormality in cysteine proteinase of the fibroblasts has been demonstrated. It seems likely that an abnormal glycosaminoglycan secreted by fibroblasts is deposited on the surface of the elastic fibres and leads to fragmentation and calcification.

In skin lesions the elastic fibres in the mid dermis are clumped, degenerated, fragmented and swollen and abnormal fibres stains positively for calcium. The collagen fibres are also abnormal being split into small fibres. Similar changes occur in connective tissues of the media and intima of blood vessels, Bruch membrane of the eye and the endocardium and pericardium. Calcification has been reported in pulmonary and other visceras3.

Vascular involvement is generalized but may involve predominantly the larger arteries, the mesenteric , renal and visceral arteries or those of the extremities. Calcification of internal elastic lamina of the arteries leads to vascular obstruction.

Skin changes: Lesion are small (1-3 mm in diameter), yellowish papule arranged on linear or reticular pattern and eventually forming plaques. Telangiectasia may be present. Areas involved are – fold of groin, arms, neck, axillary folds, armpits, perineum and mucous membrane. Skin is soft, lax, wrinkled and may hang in folds.
Eye: Angioid streaks represent defect or cracks in Bruch’s membrane. Angioid streaks are irregular jagged, curvilinear lines that radiate from the region of the optic nerve into the more peripheral retinal tissue. Other findings in PXE include salmon spots (areas of tissue atrophy) optic disc drusen (calcified deposits within the optic nerve head) and crystalline bodies (small yellow round subretinal lesions) and choroids neovascularization presented with visual loss (70%). If haemorrhage and choroiditis develops it may lead to blindness4.

Cardiovascular Changes:
• There may be intermittent claudication, diminished peripheral pulses, accelerated altheroma with hypertension5.
• Death commonly result from cerebral haemorrhage, coronary occlusion (angina/MI) or massive haemorrhage into the gut5.
• Cardiomyopathy and mitral value prolapse (5-8%) has been reported.

Associated abnormalities: May be associated with Osteitis deformans (Pagets disease) Osteoectasia, sickle cell disease, Marfan’s Syndrome and perforating elastosis.

Diagnostic criteria for Pseudoxanthoma elasticum (from Lewohl et al)6.
Major Criteria:
1. Flexural yellow cobblestone lesions.
2. Characteristic histopathological features of lesional skin using elastic tissue and calcium stains (e.g Van Gieson and Von Kossa).
3. Angioid streaks in the retina.

Minor Criteria:
1. Characteristic histological changes in non-lesional skin.
2. Family history of PXE in first degree relatives.
• It should be suspected in cases without skin lesions by obliterative arterial disease of early onset and unexplained gastrointestinal haemorrhage.
• The important aspect of treatment is to ensure that complications from blood vessels involvement are prevented or dealt with speedily by the appropriate specialist. Regular follow up with a specialist vascular surgeon and/or cardiologist is recommended.
• There is currently no effective treatment for skin lesions, but the appearance may be improved by plastic surgery.
• Restriction of dietary calcium has been tried with some benefits , but controversial.
• Laser photocoagulation, may be helpful in preventing further bleeding at the back of the eye.
• Genetic counseling may be helpful.
• Propranolol – to prevent development of aortic dilatation.

Though incidence of haematuria is reported earlier in some cases, our case primarily presented with haematuria along with other usual complications. The probable mechanisms is due to microvascular involvement of kidney and urinary tract.

1. L Frank Glass/Shelli Marks, BS: Department of Internal Medicine and Pathology, Vuniversity of South Florida College of Medicine –Nov 2003 – 05.
2. Pasquali – Ronchette L, Pincellinc et al – Arch dermatol. Res 1986, 278, 386-92.
3. Goodmen RM, Simth E W, Paton D et al – “PXE”: Clinical and histopathological study medicine, 1963, 42, 297- 334.
4. Vitreous –Retina – Macula Consultant of New York – Angioid streaks and pseudoxanthoma elasticum.
5. Parker J C, Firedman –Kien AE, Levin et al . NEJM 1964/Kundrotus L, Novak J et al ; GI bleeding in PXE Am J Gastroenterol , 1988.
6. Lebwohl et al ; J Am Aacd Dermatol, 1994.

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Creutzfeldt-Jakob Disease (CJD) is a relatively rare cerebral disorder involving rapid decrease of mental function and movement known to be caused by abnormal brain proteins called “prions”. It is the most frequent human variety of prion diseases and similar to the various transmissible spongiform encephalopathies that afflict animals including the new variant “Mad Cow Disease” (nv CJD). Prions cause devastating changes in the CNS particularly the grey matter causing neuronal loss, gliosis and diffuse fine-meshed vacuolation of the neuron containing structures.

The yearly incidence is about 1 in a million. Creutzfeldt & Jakob in the early 1920’s described six cases of human progressive dementing illness with spasticity, ataxia and involuntary movements. Bjorn Sigurdsson termed slow infection in 1954 with reference to a chronic degenerative disease of brain in sheep known as scrapie. In 1957 Gajdusek and Zigas described the illness among the fore people of Eastern New Guinea practicing ritual cannibalism. In 1982 Prusiner coined the term “prion” to describe the unconventional pathogen.7 All prion disorders are associated with aberrant metabolism of PrP, the prion protein. However, in India the first case of CJD was reported in 1965 and since then sporadic cases have been reported very often.8

We report such a relatively rare case from western Orissa with great deal of diagnostic difficulties at the out set.

S.B., a 68 year old female was admitted to a local hospital for failing memory and behavioral changes followed by lack of co-ordination and visual disturbances. She was provisionally diagnosed to be a case of Alzheimer’s Disease in early 2002. Gradually she noticed pronounced mental deterioration and involuntary movements and weakness of extremities with altered sensorium for which she was admitted to a central hospital and was treated on the line of cerebrovascular accident. On 12th February 2003 she was referred to V.S.S. Medical College, Burla for further treatment.
There was no past history of similar illness / phychiatric or neurological disorder. There was history of cataract operation with intraocular lens (IOL) implantation in August 2002. But there was no history of vaccination in the recent past. She was a newly detected diabetic and hypertensive but under control. She was married and blessed with two children, non-vegetarian by diet (no history of beef or pork intake) and no history of addiction of any kind. Family history was not suggestive.
The patient was stuporus, non-communicative, feebly responsive to painful stimuli, pulse rate 86/pm, regular, BP 130/80mmHg, afebrile, per abdomen, CVS and respiratory system revealed no abnormality.
CNS examination revealed stiffness in all the limbs, deep tendon reflex increase, myoclonus present with flexor plantar response.
Routine investigations showed Hb-11.5gm%, MP (QBC)-negative, TLC-10000/mm3, ESR-15mm, FBS-86 mg%, Serum Na + 138, Serum K + 4.3, Blood urea – 67 mg%, Serum creatinine – 1.05 mg%. CSF, urine examination and ECG were within normal limit.

CT Scan (Fig.1) was normal. The EEG (Fig.2) revealed presence of periodic complexes at an interval of less than one/second arising from both sides, which was characteristic of C.J. disease.
She was initially treated on the line of metabolic encephalopathy. During follow up the patient developed generalized tonic clonic seizures next day of admission but was controlled with anti-epileptic medication. However, there was gradual deterioration of neurological status and she died on 22-02-03 after about 10 days of hospital stay.
Sporadic form of CJD is the most frequent variety presenting spontaneously, not transmitted from person to person.6 Familial form is transmitted as autosomal dominant inheritance in 15% cases due to a point mutation in the gene encoding PrP at codon 178 producing asparagine.3 Iatrogenic form results with corneal transplants, dural grafts, intracerebral EEG recordings and recipients of human growth hormone in growth failure cases, although the incidence after cataract operation and IOL implantation have not been reported.
The clinical tetrad of CJD is subacute progressive dementia, myoclonus, typical periodic complexes on the EEG and a normal CSF.7 The cognitive impairment may be quite global in nature as evidenced by neuropsychological testing. Prodromal symptom experienced in approximately 1/4th of patients may occur weeks to months preceding onset of progressive dementia, which is the hallmark of the illness.4 Ataxia seen in 1/3rd of patients initially but ultimately occur in as many as 70% cases. In about 10% of patients the illness begins with almost stroke – like suddenness and runs its course rapidly in a matter of few weeks or months.
Heidenhain’s variant of CJD includes cortical blindness and visual agnosia where as in Brownell and Oppenheimer variant cerebellar ataxia with a relative paucity of cognitive impairment (17%) dominates, Dyskinesias, prominent extrapyramidal features, seizure, LMN features, autonomic dysfunction, stroke-like presentations and supranuclear gaze palsies are some of the exceptional presentations.7 Jakob type of CJD is the cortio-striato-spinal variant where as the lesion in the diffuse variety (Stern and Garcin) lies in the basal ganglia and thalamus. Besides in the panencephalitic form there is involvement of white matter out of proportion to the degeneration of grey matter.4
Only the electro-encephalogram is of diagnostic significance amongst all routinely available laboratory studies. In well advanced disease 1-2 cycles per second triphasic sharp waves superimposed on a depressed background are characteristic. These periodic sharp waves are asymmetrical tend to become slower with progressive course of the disease. This is evident within 3 months of onset in approximately 80% cases. A non-specific abnormality in the form of symmetrical theta and delta waves on an irregularly depressed background may be seen before the occurrence of periodic sharp waves in about 50% cases. Often episodic burst suppression high voltage activity is seen which is less specific and rare during the early course.5
CFS parameters are usually normal and imaging studies of brain remain normal in majority of patients. Cerebral atrophy may be noted occasionally on MRI.1 Positron emission tomography (PET) in few cases shows regional hypometabolism of glucose reflecting loss of neuronal function. Brain biopsy specimen for neuropathologic study is the definitive diagnosis revealing a fine-meshed spongy vacuolation and should be carried out if thought by the physician with due consent by family members as the disease is invariably fatal. However, a finding of normal tissue morphology does not exclude the disease and in such situation typical EEG abnormality can lead to a correct diagnosis.2
As such caution should be maintained while operating for cataract and if any IOL is planned for the patient, the transmission of CJD should be kept in mind.
1. Esmonde TFG : Will RG MRI in CJD : Ann. of Neurology, 1992; 31:230-1.
2. Gertz HJ; Henker H : Cervos Navarro J : CJD disease : correlation of MRI and Neuropathological findings : Neurology : 1988; 38 : 1481-2.
3. Goldfarb LG, Petersen RB, Tabaton et al, Fatal familial insomnia and familial creutz feldt Jakob disease : Disease phenotype determined by DNA polymorphism. Science : 1992:258:806-8.
4. Kretzschmar HA : Human prion Diseases (Spongiform encephalopathies) Arch Virol supplementum : 1993; 7:261-293.
5. Levy SR, Chiappa KH, Burke CJ, Young RR. Early evolution and incidence of EEG abnormalities in CJD. J. Clinic. Neurophysiol. 1986; 3 : 1 – 21.
6. Masters CL, Gajdusek DC : The spectrum of CJD and the virus inducd subacute spongiform encephalopathies. In Smith WT, Cavanagh JB (Eds) Recent Advances in Neuropathology, Churchill Livingston, Edinburgh 1982: p-139.
7. Prusiner SB, Human Prion Diseases : Ann. Neurology, 1994a; 35:385-95.
8. Shankar SK; Satish Chandra P : Creutz feldt Jakob disease in India – A report Neurology India : 1988; 36, 279-283.

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Symmetric peripheral gangrene (SPG) is a rare clinical presentation in case of falciparum malaria. Few cases have been so far reported from India and abroad. Here we report such a case from this hospital and discuss the pathophysiology and management.


Symmetric peripheral gangrene (SPG)
Falciparum malaria
Disseminated intravascular coagulation (DIC)


SPG is an uncommon clinical condition characterized by sudden onset of symmetric dry gangrene of acral distribution without any evidence of vasculitis or arterial obstruction. This has been described in conditions like infections most commonly bacterial (meningococcal, streptococcal, Pneumococcal, E.coli septicaemia) and viral (varicella and viral gastroenteritis), low output states like myocardial infarction, shock, CCF or use of drugs like vasopressin and ergot and other conditions like polymyalgia rheumatica,cryoglobinaemia. In all these conditions DIC has been the basic pathogenesis (90%)9.

The incidence of DIC and SPG in cases of falciparum malaria has rarely been reported as one of its multiple complication1.

A 15 years boy from Raigarh (C.G.) admitted to this hospital in last week of December 2005 with history of fever associated with chill and rigor (20 days), sudden blackening of distal parts of fingers, toes of all limbs , tip of nose and lateral part of pinna of both ears (15 days) and altered sensorium for 3 days. He was treated at the local hospital with I/V fluid, antibiotic and decadron , without any improvement.

There was no history of joint pain, trauma, sore throat, spontaneous bleeding, thromboembolic episode or any relevant disease like SCD, HTN, DM. He was a student in a residential school without habit of smoking or alcohol. There was no relevant family history.

On examination the patient was stuporous with Temperature 1000F , pulse – 100/min , regular low volume and all the peripheral pulsations well felt without brachiofemoral delay. BP was 110/70 mm of Hg (both U/L), with moderate pallor and features of dehydration. There was no icterus , clubbing, lymphadenopathy or thyromegaly. Cardiovascular and Respiratory system revealed no abnormality. There was no hepatosplenomegaly. Neurological examination revealed mild neck rigidity with diminished DTJ and plantar was flexor. Examination of skin and digits showed blackening of tip of nose (Fig.1), both ear pinna on lateral aspects (Fig 2) and distal parts of toes and fingers of all limbs (dry gangrene) (Fig 3 & 4). There was clear line of demarcation between the healthy and affected parts.

Investigation on the day of admission showed
Hb: 6.2 gm%
DC : N - 48, E-2, L-48, M-2, B-0
TLC: 9800/mm3
TPC: 60,000/mm3
RBS : 116mg%
B. Urea : 96mg%
Serum Creatinine : 1.5mg%
Blood smear : Showed P.falciparum rings and gametocytes
Serum Bilirubin : Total 0.78mg%
Direct 0.26mg%
SGPT : 36U/L
Alkaline phosphatase: 50U/L
Electrolytes: Serum Na+ - 138meq/L
Serum K+ - 3.6meq/L
Serum Ca++ - 8.5 mg/dl
Prothrombin time (PT) – 16 second (control 12.5)
Activated partial thromboplastin time (aPTT) 29.5 seconds (control – 28)
Fibrinogen : 187mg/dl (N : 250-450mg/dl)

The patient was treated with injection Artesunate, injection Ceftriaxone 2gm I/V BID,injection Omnacortil, Injection Ranitidin 8 hourly, I/V fluid and tablet Zilast (Cilostazol 100mg BID) with care of the skin , bladder, bowel and maintaining nutrition. He was stabilised on 2nd day and gained consciousness and there was clinical improvement. Two units of whole blood transfusion given.

On further investigation urine analysis was normal and haemoglobin electrophoresis was AA (to exclude SCD – common in this belt). USG of abdomen and pelvis was normal. Test for antinuclear factor, LE cell, Rheumatoid factor, VDRL were negative, Test for cryoglobulin was normal. Coagulation profile (Antineutrophil cytoplasminc antibodies, Antinuclear antibodies, anti double standard DNA, complement –3 , complement – 4) was normal. Serum uric acid was 3.9 mg/dl.

Echocardiography did not reveal any thrombi or vegetation. The Doppler study of the vessels demonstrated normal flow pattern upto digital arteries in all four limbs.

Biopsy of an affected area of the skin showed thrombi in dermal capillaries without any evidence of vasculitis.

Blood could not be tested for fibrin degradation products (FDPs). However evidence of DIC was seen in skin biopsy.

Gradually the patient improved. Full anti-malarial course was given and antibiotic was given for 7 days. Zilast was continued and omnacortil was gradually tapered. Slowly the gangrenous parts improved and patient was discharged on 12th day. No surgical intervention was required.

SPG has been reported in various medical conditions including falciparum malaria1, 7, 4, 2, 6,12. Our patient had no clinical or laboratory evidence of other causes like sepsis, vasospastic condition, ergot or other drugs. There was no evidence of vasculitis, cryoglobulinaemia, polycythemia or thrombocythaemia. The common pathogenic mechanisms of SPG is DIC9. All the cases reported had evidence of DIC.

Reduced fibrinogen level, thrombocytopenia, prolonged PT, prolonged aPTT and histopathological evidence of microvascular thrombi indicate the presence of DIC in this patient1.

Alteration of coagulation and fibrinolytic system in falciparum malaria is well recognized5. A functionally active but controlled coagulatory state exists in falciparum malaria even in uncomplicated cases5. Elevation of FDPs reflecting the ongoing fibrinolysis have been documented11. Heavy parasitaemia triggering the coagulation pathway10, alteration in the lipid distribution across the surface membrane of the parasitized erythrocytes activating the intrinsic coagulation cascade8 and activation of complement system5 have been postulated as possible mechanism for DIC in falciparum malaria. Sequestration of the parasitised erythrocytes in the microcirculation by molecular interactions with endothelial receptors, mainly intracellular adhesion molecule10 – 1(ICAM – 1) may occur. Rosetting of the healthy erythrocytes around parasitised red cells may occur and these multicellular aggregates further exacerbate the vascular obstruction caused by sequestration3.

DIC is encountered in less than 10% of patients with cerebral malaria3 and manifest as spontaneous bleeding from gum and GIT. But in a review of 71 cases of SPG and DIC significant bleeding complications were not recorded9.

Our patient who had no other cause of peripheral gangrene made satisfactory recovery on specific antimalarial therapy supporting the observation that falciparum malaria was the triggering mechanism for the DIC and subsequent SPG.


In conclusion we report that falciparum malaria may present as peripheral dry gangrene and this possibility though uncommon must be taken into consideration while encountering patients in endemic areas.

1. Anuradha S, Prabhash K,Shome DK et al . Symmetrical peripheral gangrene and falciparum malaria an interesting association. JAPI 1999; 47(7): 733-5.
2. Arya TVS, Singh SP, Singh DK. Bilateral foot gangrene occurring in falciparum malaria. JAPI 1990; 38: 30 (Abstract).
3. Bradley D, Newbold CI, Warell DA. Malaria in Oxford Test Book of Medicine. Weatherall DJ Ledinqham JGG and Warrell Da (eds) Oxford University Press Inc. New York 1996; 1 : 835-63.
4. Chittichai P, Chiekrul N, Davis TM. Peripheral gangrene in nofatal paediatric cerebral malaria: a report of two cases. Southeast Asian Trop Med Public Health 1991; 22: 190 – 4.
5. Clemens R, Pramoolsinsap C, Lorenz R et al . Activation of coagulation cascade in severe falciparum malaria through the intrinsic pathway.Br. J. Haemat. 1984; 87,100-05.
6. Jain D, Srivastava S, Singhal SS. A rare presentation of falciparum malaria . JAPI 1995; 43: 582.
7. Kochar DK, Shubhakaran , Kumawat B et al. A patient with falciparum malaria and bilateral gangrene of the feet who developed arrhythmia/ventricular fibrillation after quinine therapy. Quart J Med 1998 (Corrosp)246.
8. Mohanty D, Marwah N, Gosh K et al. Vascular occlusion and disseminated intravascualr coagulation in falciparum malaria. Br. Med J 1985; 290: 15-6.
9. Molos MA, Hall JC. Symmetrical peripheral gangrene and disseminated intravascualr coagulation. Arch Dermatol 1985; 121: 1059-61.
10. Philips RE, Looareesuwan S, Warrell DA Et al . The importance of anemia in cerebral and uncomplicated falciparum malaria: role of complications dyserythripoiesis and iron sequestration. Quart J Med 1986; 58: 305 – 23.
11. Rojanasthein S, Surakamolleart V, Boonpucknavig S et al . Hematological and coagulation studies in malaria. J. Med Assoc. Thai 1992; 75 (supplele-1):190-4.
12. Sharma BD, Gupta B. Safdarjung Hospital, JIACM 2002, 3(3): 297 – 9.

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Fish is a very common and tasty food and at the same time very nutritious too. There have been many cases of food poisoning after intake of poisonous fishes. Here we report one such case where 8 people got admitted to V.S.S. Medical College Hospital, Burla after consuming some kind of fish developed signs and symptoms of tetrodotoxin food poisoning. Among those 8 patients 2 of them expired.

Food poisoning, Ich thyotoxicosis, Tetrodotoxin, Puffer fish

Fish is a very delicious food throughout the world, which is widely consumed. There are two categories of fishes-marine and fresh water. Few people know about the toxins present in the fish of both categories. The poisonous fishes are morphologically different from other edible fishes. The study of toxin of fish is known as Ichthyotoxicosis which is an important part of food poisoning. It is very important to know the toxins present in the fish so that fish can be taken as healthy food.

Here is an important case of food poisoning consumed by local tribals and admitted to V.S.S. Medical College Hospital and the end result is described below.

On 18/10/2007 total eight people came to casualty around 8.30PM with history of taking one kind of fish in a social function. Locally known as “Fukka” and their signs and symptoms which developed within half an hour of intake such as paresthesia, vomiting, abdominal pain, breathlessness, dysphagia and extreme weakness of 4 limbs. In past history there was no history suggestive of diabetes mellitus, hypertension, sickle cell disease, bronchial asthma. In personal history there was no history of any addiction and they were from poor socioeconomic status.

The common clinical signs presented in such patient are respiratory rate: 25-30/min, BP - 100/70 to 110/80 mm of Hg , Pulse rate- 96- 104 /min regular and low volume. Per abdominal examination no abnormality detected. Chest examination bilateral vesicular breath sound and no added sound. Cardiovascular examination revealed first and second heart sounds normal and no murmur heard. The central nervous system examination revealed patients irritable and anxious with ptosis (B/L), pupils (B/L) normal in size and normally reacting to light, tone of the muscles of limb decreased and power of muscles of limbs Grade 2, plantar no response (B/L) and no meningeal signs.

On investigation of the patients Hb – 10-12gm%, ESR - 6 -10 mm (1st hour) DC, TLC within normal limit. Serum creatinine 0.8 – 1.0 mg/dl, blood urea 26-34 mg/dl, serum Na+ 136-140 meq/L, Serum K+ 4.0 – 4.6meq/L, urine routine and microscopic examination within normal limit. Random blood glucose 140mg/dl and ECG within normal limit.

The following treatment was given like stomach wash with KMno4, Oxygen inhalation, injection atropine and injection neostigmine alternately every 15 minute, injection ceftriaxone and injection hydrocortisone (100mg) IV 8 hourly, injection deriphylline 1 ampoule IM 8 hourly, injection ranitidine 1 ampoule IV 8 hourly, IV fluids, cathetrization of bladder and ryles tube were administered under sterile technique.

Course of treatment:
Out of 8 patients 2 became very serious like respiratory distress with laboured and hurried respiration along with frothing from mouth and coarse crepitations heard bilateral in lung fields. The 2 patients became stuporous leading to coma and death at 8 AM next day in spite of cardiopulmonary resuscitation. The signs and symptoms of other 6 improved gradually and they had an uneventful recovery and were discharged after 4 days.

Postmortem findings:
The two cases were subjected to medicolegal autopsy and the autopsy findings were:

External features: Face livid, frothy, blood tinged discharges from nostrils, eye closed, pupil dilated and fixed, nail bed cyanosed, rigor mortis all through the limbs.

Internal features: In both case stomach contained 100ml of brownish liquid, the mucus membrane were congested without excoriation. Liver, spleen, kidney were intensely congested. Right chamber of heart contained clotted blood and left chamber empty, great vessels were empty. The cause of death was established as asphyxia as a result of respiratory failure.

The final cause of death was pending chemical examination of visceras. For that stomach with its content, 500 gm of liver, intestine 30 cm and half of each kidney were preserved in saturated solution of common salt and handed over the police to further transmission to chemical examination.

The relative were advised to bring the particular fish which they have consumed and the fish was identified as puffer fish (Photo 1, 2).

The fish consumed by eight people were identified to be Puffer fish after morphological examinations of the fish they have brought. Its local name is “Fukka”. In Japan a local variety of Puffer fish called “Fugu” is considered a delicacy but it requires special training and licensing of preparation as they are poisonous1. These fishes contain a toxin known as tetrodotoxin which is a heat stable, non protein neurotoxic predominantly concentrated in ovaries, kidneys , fish skin, muscles and intestine of Puffer fish2. Describing in detail tetrodotoxin is water soluble and its chemical nature is aminoperhydroquanizole1.

The ovary’s high concentration of the toxin renders female more poisonous during spawning season7. The toxin can be detected by mouse bioassays and fluroscent spectrometry1. The tetrodotoxin resembles another toxin called saxitoxin, from which it is distinguished by heat stability up to 1000C in acidic medium5.

The action of tetrodotoxin is more prolonged but saxitoxin is more neurotoxic5. Neurotoxicity of tetrodotoxin is due to inhibition of sodium potassium pump activity and blockade of neuromuscular inhibition1. The blockade at motor end plate is competitive and reversible2.

The clinical features of tetrodotoxin fish poisoning begins shortly after ingestion (10-45min) such as paresthesia of the lips, face , toes and fingers, vomiting, light headedness, feeling of doom, diaphoresis, dysphagia and dysarthria2. Buccal bullae, salivation, cranial nerve palsies and even convulsion have been reported1. An ascending paralysis develops with respiratory paralysis as a preterminal event (6-24 hours) of post ingestion2. In serious poisoning hypotension, cardiac dysarythmias like bradycardia were also observed1.

Diagnosis is mostly done from history and clinical presentation and treatment is mostly symptomatic and supportive7. Removal of toxin by stomach wash, IV edrophonxium or IM neostigmine restores muscle strength2. Airway intubation and ventilators are necessary if patients develops respiratory paralysis6. Studies have shown that mortality has approached 60%2.

Burla is situated on the bank of river Mahanadi. In past 2 years zoologist have found out that in river Mahanadi and its tributaries there is increase in tetrodotoxin containing fishes which were not seen 10 years ago. This is because of favourable temperature and pH of water of Mahanadi and its tributaries that caused an explosion of population of puffer fishes. This is because of construction of various factories in nearby areas for which the flora and fauna of Mahanadi river is getting rapidly destroyed and along with there is decreased species of fresh water fishes in resorvior (Dainik Samaj 01/11/2007).

In spite of fish being a very much proteinous food it can kill human beings with its toxins as described above. It is a staple food in costal districts of Orissa, which cannot be replaced with any other food because it contains excellent and excessive protein. So we have to take some prevention for abetting the toxin found in the fish.

Tips to prevent fish poisoning:
1. Avoid eating large tropical fish like shark, barracueda, red snapper, dear bass etc5.
2. Do not consume fish that are likely to have decomposed i.e. fish that have not been stored or preserved properly5.
3. Do not eat the viscera of fish (particularly liver and gonads). See that the fish is properly cleaned and cooked5.
4. It has been suggested that suspect fish be first fed to a cat. If the cat dies within 8 hours, it is an explicit indication that fish is toxic5.
5. Do not eat unidentified fishes.
1. Gold Frank’s Toxicologic Emergencies, 6th Edition, P 1169-1170 by Lewis R Goldfrank, Neal E Flomenbaum, Richard S Weisman, Mary Ann Howland, Rober S Hoffmann, Neal A Lewin.
2. Medical Toxicology Diagnosis and Treatment of human poisoning Pg 1197-1198 by Mathew J Ellenhorn , Donald G Barcelous.
3. Modi’s Medical Jurisprudence and Toxicology, 23rd Edition by K Mathiharan & Amrit K Pattnaik.
4. Modern Medical Toxicology by V.V. Pilli.
5. Mosher HS, Fuhrman FA, Buchwald HD et al; Tarichatoxin – tetrodotoxin , A potent neurotoxin science 1964; 44; 100-1110.
6. Sims JK, Ostman DC, Puffer Fish poisoning : Emergency diagnosis and management of mild human tetrodotoxication: Ann Emerg Med 1986; 15:1094-1098.
7. Torda TA, Sinclair E, Ulyatt DB, Puffer fish (Tetrodotoxin)poisoning clinical records and suggested management. Med J Aug 1973; 1: 599-602.

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Hydatid cysts are due to parasitic infection caused by the cestode tapeworm Echinoccocus. In humans the hydatid disease commonly involves the liver (75%) & the lungs (15%). The remaining (10-15%) cases involve the other organs of the body-kidney, spleen, heart, brain, bones, pancreas, breast, ovaries, scrotum, thyroid gland, inguinal canal & soft tissues.The disseminated intra-peritoneal hydatid disease is a very rare finding1. We report such a case wherein the abdominal cavity is seen to contain multiple hydatid cysts .Hydatid cysts were also found in the left scrotum, lungs, liver & spleen.

Hydatid cyst, Echinococcus, Peritoneal hydatidoses, Scrotum

A 42 years Hindu male presented with complaints of left scrotal swelling for 6 months, progressive distention of abdomen for 1 year & generalized weakness for 1 ½ years. He had past history of hydatid disease 13 years back, for which cystectomy was done in 1994. He was not taking any drugs. There is no history suggestive of diabetes mellitus, hypertension, tuberculosis, coronary artery disease or history of Filariasis.

On examination, patient was of thin built with blood pressure 110/70 mmHg (both upper limb), pulse rate 84/min (Regular), Respiratory rate of 24/min and temperature of 37oC. He had diminished vesicular breath sounds in both lower lung fields. His abdomen was distended. On inspection, dilated veins were present over the abdomen with flow below upwards. There was a mid line supraumblical scar mark. Flanks were full and contour was irregular. Umblicus was central and everted (Figure 4). On palpation, there was no local rise of temperature, no tenderness, no fluid thrill and shifting dullness. There were multiple ill defined cystic masses all over the abdomen of varying size. There was bilateral scrotal mass which was soft and non-tender with increased scrotal volume. The liver was not enlarged and spleen was not palpable. On auscultation, bowel sound was normal, no bruit heard. Cardiovascular system and central nervous system examinations were within normal limit.

Hb%-10.4gm%, TLC-12,000/mm3, N50E28L22, ESR-48mm(1st hours), FBS-74mg/dl, Blood urea-31mg/dl, Sr creatinine-1.58mg/dl, Sr Na+-143meq/lt, Sr K+-4.9meq/lt, Urine analysis-normal study,ECG-normal.

Sr Billirubin (total)-0.89mg/dl, Direct-0.22mg/dl, Indirect-0.67mg/dl, SGOT-26.39IU/lt, SGPT-18.40IU/lt, Sr Alkaline phosphatase-149.38IU/lt, HBsAg-negative, Anti HCV Ab-negative.

Multiple hydatid cysts of liver, spleen, left scrotum & through out abdomen, varing from size 1 mm to 6 mm, B/L moderate Hydrocele (Figure 3).

Circular opacity of size 8x2cm in right basal zone (? hydatid cyst).

Multiple hydatid cyst of liver, spleen, B/L lower lobes of lungs, involving mesentery & retoperitoneal region. Nonvisualization of RT kidney
(? replaced by hydatid cysts) (Figure 1, 2).


Echinococcus antibody titer - 1:64 (Normal 1:32)

Surgical resection of the cysts was not possible. Albendazole-400 mg PO BD for life long (with monthly monitoring of Liver function Tests) given. On first two follow ups there was decrease in the abdominal distension & the liver function test was normal.

Hydatid disease is a parasitic infection caused by the Echinococcus granulosus. The dogs are the definite host and the adult worms are found in their small intestine. Human get infected either by contact with the definitive host or by consuming vegetables and water, contaminated with the hydatid ova2. Hydatid disease is endemic in the cattle grazing areas like India, Pakistan, Middle-East, Africa, South America, and New-zealand1. The close association of people with sheep and dogs and the unavailability of clean potable water supplies in India make it a region endemic to disease. Majority of the cases of Hydatid disease seen come from rural areas or people who have settled in urban centers after spending life in villages. Most of the people acquire the disease during their childhood, but do not present with the clinical signs and symptoms until late adult hood. The natural progression of an untreated cyst may include calcification and death of the cyst; however, more frequently the cyst gradually enlarges3.

The liver (75%) and the Lungs (15%) is the commonest site of involvement, although no site in the body may be completely immune from it4. This atypical and rare presentation of the disease may be seen in kidneys (3%), usually the upper and the lower pole of the kidney may be involved. The spleen may be involved in about 4% of the cases and is associated with splenomegaly, fever and abdominal pain4. Cerebral Hydatid cysts occur in only 2% of all the cases reported. The region of the middle cerebral artery distribution specially the parietal lobe is most frequently involved. Cardiac Hydatid cyst is very rare (0.02-2%) and most commonly affects the left ventricular chamber specially the left ventricle in 50%-60% of cases4. The other sites that have been reported to be involved are bones, pancreas, breast, ovaries, scrotum, thyroid glands, inguinal canal and soft tissues.

Hydatid cysts can also be found rarely in the peritoneum1. Most of these cases are the result of traumatic or surgical rupture of a hepatic, splenic or mesenteric cyst. The prevalence of peritoneal hydatid cysts in cases of abdominal Hydatid disease is approximately 13%. In our case the patient had already undergone cystectomy and it is likely that these findings may be associated to previous surgical rupture, although spontaneous rupture of micro cysts into the peritoneum may also occur in about 12% of the cases1. The hydatid cysts may resemble a multiloculated mass filling the entire peritoneal cavity. Such a condition is referred to as peritoneal hydatidoses .

Hydatid cyst may be solitary or multiple. The type of the imaging modality used depends on the site and the size of the hydatid cyst. Ultrasonogarphy (USG) is the first line of screening for abdominal hydatidosis and it is especially useful for detection of cystic membrane, septa, and hydatid sand. CT scan best demonstrates cyst wall calcification and cyst infection. CT scan imaging is also the modality of choice in peritoneal seedling1. The CT scan shows well defined solitary or multiple cysts that may be thin walled or thick walled. A hydatid cyst typically demonstrates a high attenuation value at unenhanced CT even without calcification. Multivesicular cysts can depict a typical honeycomb pattern. The septa represent the walls of the daughter cysts housed within the mother cyst. A “wheel spoke” pattern can be observed when the daughter cysts are separated by hydatid matrix1.

There are different types of serological tests which can be carried out for the diagnosis, screening and follow up of patients with hydatid disease. These include the immunoelectrophoresis, enzyme-linked immunosorbent assay (ELISA), latex agglutination and indirect haemagglutination (IHA) test 4. The diagnosis of HD can thus be established with the help of radiologic and serologic finding4. The diagnosis is also easier when the lesion has multiple locations involving different organs or when daughter cysts, germinal membrane detachment and calcification are present 2.

Surgery is the mainstay of treatment for hydatid cysts of the Liver. Laparotomy is the most common surgical approach6. Liver resection and pericystectomy are procedures that resect the closed cysts with a wide safety margin; however they are considered too radical procedures for hydatid cyst removal. Conservative procedures such as cystectomy and omentoplasty for hydatid disease should be the standard surgical procedure because of their safety, simplicity, and effectiveness in fulfilling the surgical treatment criteria of hydatid disease6. The peritoneal hydatidosis has also been successfully surgically removed with similar conservative procedures5, 7.

Symptomatic or large cysts should be surgically treated. In cases suspected of having peritoneal spillage, antihelminthic drugs should be administered8. In addition, small asymptomatic cysts, some daughter cysts, and peritoneal secondary cysts and splenic cysts may also be effectively treated with Albendazole8.


1. Pedrosa I, Saiz A, Arrazola J, Ferreiros J, Pedrosa CS. Hydatid disease: radiologic and pathologic features and complications. Radiographics 2000; 3:795-817.
2. Polat P, Kantarci M, Alper F, Suma S, Koruyucu MB, Okur A.: Hydatid Disease from Head to Toe. Radiographics 2003; 23:475-94.
3. Ammann RW, Eckert J. Cestodes. Echinococcus. Gastroenterol Clin North Am 1996; 3:655-89.
4. Husen YA, Nadeem N, Aslam F, Bhaila I. Primary splenic hydatid cyst: a case report with characteristic imaging appearance. J Pak Med Assoc 2005; 5:219-21
5. Karavias DD, Vagianos CE, Kakkos SK, Panagopoulos CM, Androulakis JA. : Peritoneal echinococcosis. World J Surg 1996; 20:337-40.
6. Buttenschoen K, Carli Buttenschoen D. Echinococcus granulosus infection: the challenge of surgical treatment. Langenbecks Arch Surg 2003; 4:218-30.
7. Hamamci EO, Besim H, Korkmaz A. Unusual locations of hydatid disease and surgical approach. ANZ J Surg 2004; 5:356-60
Balik AA, Celebi F, Basglu M, Oren D, Yildirgan I, Atamanalp SS. Intra-abdominal extrahepatic

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