Review on Euphorbia neriifolia Plant

Abstract

The present review is an attempt to highlight of Euphorbia neriifolia – Indian ethno-medicinal plant which was to be scientifically proved with different pharmacological activities such as laxative, carminative, bronchitis, tumors, leucoderma, piles, inflammation, enlargement of spleen, anemia, ulcers, fever and for wound healing along with some harmful effect to human being especially latex of plant.

Keywords: Euphorbia neriifolia; Herbal drugs; Medicinal plants; Wound management, Latex

Introduction

Medicinal plant usage is as old as humankind in the therapeutics. There are about 45,000 medicinal plants species in India. The officially documented plants with medicinal potential are 3000 but traditional practitioners use more than 6000. Bioactive compounds in plants have also been utilized for additional purposes, namely as arrow and dart poisons for hunting (several Aconitum species), poisons for murder, hallucinogens used for ritualistic purposes, stimulants for endurance, and hunger suppression, as well as inebriants and medicines. The plant chemicals (bioactive compounds) used for pharmacological or toxicological effects are largely the secondary metabolites. These secondary metabolites called bioactive compounds can be classified into several groups according to their chemical classes, such alkaloids, terpenoids, cardiac glycosides, saponins, steroids, limonoid, tannins, flavonoids, and phenolics [1]. In 18^th century and before that, the plants are major source for the treatment of different diseases and infections.

Now a day’s some of the plant derived natural products that includes vinblastine, vincristine, taxol, podophyllotoxin, camptothecin, digitoxigenin, gitoxigenin, digoxigenin, tubocurarine, morphine, codeine, aspirin, atropine, pilocarpine, capscicine, allicin, curcumin, artemesinin and ephedrine among others are also used as drug in pure form or in crude form or mixture. Some of them are synthesized synthetically but about 121 (45 tropical and 76 subtropical) major plant drugs have been identified for which no synthetic route is currently available (Figure 1).

Figure 1:

According to the World Health Organization (WHO) till 2003 about 80% of the population of developing countries are unable to afford pharmaceutical drugs, so they goes to plant based medicines to sustain their primary health care needs [2]. 252 drugs are considered as basic and essential by the WHO and out of those 11% are exclusively of plant origin and a significant number are synthetic drugs obtained from natural precursors. India has an official recorded list of more than 45,000 plants species and estimated list of more than 7,500 species of medicinal plants growing in its 16 agroclimatic zones under nearly 63.7 million hectares of forest courage [3].

Euphorbiaceae, the spurge family, comprises five subfamily, 49 tribes, some 7300 species and 283 genera of flowering plants distributed primarily in the tropical regions [4,5]. The largest genus of family Euphorbiaceae is Euphorbia with about 1600 species. They range from annual weeds, vines, succulents, herbs (Phyllanthus amarus), shrubs (Ricinus communis) and trees (Phyllanthus emblica). In several species of Euphorbia, the stem is modified to perform photosynthesis. There are more than 35 species are found in tropical, subtropical and warm temperate regions of South-East Asia; Vietnam has more than 24 species, Thailand has 25, Sumatra has 6, Java has 5, Borneo has 5, Philippines has 6, Sulawesi has 5, Lesser Sunda Islands has 11, Moluccas has 7 and New Guinea 15, Australia has 45 species [6]. In our country, the family is represented by several genera such as Euphorbia, Ricinus, Phyllanthus, Croton, Pedilanthus, etc. It is characterized by the presence of white milky latex that exudes when broken and which is more or less toxic, and some are useful as a source of oil or wax. The flowers are always unisexual. The leaves are stipulate or exstipulate, petiolate, alternate (e.g. Ricinus communis), simple, entire or deeply lobed or trifoliately compound (e.g. Hevea brasiliensis) and with unicostate or multicostate reticulate venation. In xerophytic species of Euphorbia, leaves are reduced or absent.

The Euphorbia is named after a Greek surgeon called Euphorbus. He was physician of Juba II who was the Romanised king of a North African kingdom, and is supposed to have used their milky latex as an ingredient for his potions. The latex of these species has different medicinal application along with some poisonous effect. Euphorbia neriifolia Linn (Indian Spurge tree, Hedge Euphorbia commonly known as Snuhi) belong to the family Euphorbiaceae, is one of the different species of Euphorbia genus plants, with wide range of local medicinal uses throughout the areas in which it is grown. This is one of the herbs extensively used in the Indian system of medicine. They all have latex and a unique flower structure. Euphorbia neriifolia plant is reported to contain sugar, tannins, flavonoids, alkaloids, 24-methylene cycloartenol, triterpennoidal saponins, etc. As Euphorbia neriifolia plant is selected for the review because of wide variety applications in the traditional medicines such as for the treatment of abdominal troubles, bronchitis, tumors, leucoderma, piles, inflammation, enlargement of spleen, anemia, ulcers, fever and in chronic respiratory trobles [7]. It used as analgesic, hepatoprotective, immunostimulant, anti-inflammatory, mild CNS depressant, wound healing, redioprotective agent [7]. A significant percentage is succulent, but they are mostly originating from Africa and Madagascar.

Different Names of The Plant

a) Hindi name – Sehund, Danda thukar [8].

b) English name – Common milk hedge, Holy Milk Hedge, Dog’s Tongue

c) Arabic name – Jakum

d) Kannada name – Male kalli

e) Marathi name – Thor, Tridhara Nivdunga

f) Malayalam name – Illa kalli

g) Punjabi name – Thor

h) Telugu name – Akujemuddu

i) Tamil name – Ilaikalli

j) Sanskrit – Snuhi

k) Latin – Euphorbia neriifolia

l) Ayurveda – Sthavara visha varga, Upavisha

Plant Profile

a. Botanical name: Euphorbia neriifolia

b. Family: Euphorbiaceae

Scientific Classification

A. Kingdom: Plantae

B. Subkingdom: Tracheobionta (Vascular plants)

C. Superdivision: Spermatophyta (Seed plants)

D. Division: Magnoliophyta (Flowering plants)

E. Subfamily: Euphorbioideae

F. Tribe: Euphorbieae

G. Class: Magnoliopsida (Dicotyledons)

H. Subclass: Rosidae

I. Order: Malpighiales (Figure 2)

Figure 2: Genus: Euphorbia

Species [9]:

a) E. nerifolia linn – Patra Snuhi

b) E. nivulia Buch – Ham

c) E. antiquorum Linn – Tridhara Sehunda

d) E. trigona Haw – Tridhara Sehunda bheda

e) E. royleana Boiss – Thuhara

f) E. Tirucalli– Kanda snuhi

Distribution

Euphorbia neriifolia grows widely around the dry, rocky and hilly areas of north, central and South India mostly in Deccan Peninsula and Orissa. It is indigenous plant of South Asia, but now locally cultivated and naturalizing in Sri Lanka, India, Burma (Myanmar), Bangladesh, Thailand and throughout the Malaysian region except for Borneo; also occasionally cultivated in other topical regions. It is also found in E. Asia – S. China, Vietnam, and New Guinea [6]. Euphorbia is an herb and deciduous. The parts of the plant that grow above the ground are used to make medicine.

Morphological Description

Euphorbia neriifolia is cultivated in gardens, and is apparently spontaneous. Small erect fleshy glabrous shrub, erect, branches ¾ in diameter jointed cylindric or obscurely 5-angled with sharp stipular thorns arising from thick subconfluent tubercles in 5 irregular rows like cactus. The branches are 2-4 meters high, the trunk and older branches are grayish and cylindrical; medium branches are being slightly twisted, stoud, freshy, and 4 or 5 angled or winged; younger ones are usually 3-winged, wings labulate with a pair of stout, sharp, 2- to 4- mm long spines rising from the thickened bases at each leaf of petioles-scar [7]. Leaves are succulent, deciduous, 6-12 inch long, terminal on the branches, waved narrowed into a very short petiole. The leaves are arise from the sides of wings towards the end of the branches, are fleshy, oblong-obviate, 5-15cm long, or in young plants somewhat longer, painted or blunt at the tip [7]. This plant is leafless for most part of the year, except during monsoon when fresh leaves appear.

Inflorescence or the arrangement of flowers in a bunch on the plant is “cyathium” type, means one female and several male flowers are found on a same bunch. Female flowers consist of a trichambered ovary, which usually elongates in fruits. Male flowers many, bracts linear. Female flowers rarely developed. Each chamber contains an ovum. Involucres are yellowish 3-nate, the lateral ones of the cymes shortly thickly pedicelled, central sessile; lobes large, erect, roundish, cordate, fimbriate; glands transversely oblong; bracteoles most abundant, fimbriate. Fruits are three chambered, tricoccaus, but so deeply divided that it has the appearance of 3 radiating slender follicles.

Botanical Description [10]

Euphorbia neriifolia, is a bitter, xerophytic, prickly, succulent shrubby, fleshy, large, erect much branched shrub, which sometimes grows into a small tree of 2-8 meters height or more with rounded branches cactus like plant. The tree looks somewhat like a cactus but with large, persistent leaves on younger parts of the plant, and growing up to 8 meters [4,11].

Stem: Green and cylindrical stem and large branches also being round and terete, spiral ridge portion, Sharp stipular thorns, with hollow space in centre containing white reticulate mass. The younger branchlets are somewhat verticillate, with two or more whorls without articulations, fleshy, cactus-like, swirled, light-green, glabrous, 8-30 (-40) mm thick, often leafless, and spine shield in 5 distinct rows on more or less distinct angles (not winged) which are visible for a long time [12]. The trunk and older branches are being grayish and cylinder. Bunches of succulent thick leaves occurs on the branches [4]. Central meristem is prominent throughout plastochronic phases. There is close histogenic relationship between central and peripheral meristem [13]. The leaves arise from the sides of wings towards the end of the branches.

Leaves: The fresh young leaves are simple, dark green in colour having leathery texture. The surface is glabrous with reticulate venation. The average leaf size is (8-14±2) cm (length) and (4- 8±2) cm (breadth) and (1.3±0.2) mm (thickness) with pointed and acute tip [14]. Peri-clinical divisions in the third and fourth layers of peripheral meristem initiate the leaf [4]. During vegetation period they are deciduous but in the late summer they fall.

Stippular thorns: The spines are short, about 4-12 mm long arising from the ribs, grayish brown to black in color, sharp, persistent, from low conical truncate distant, spirally arranged tubercles 2-5 mm height and 2-3 cm apart [4,12].

Flowers (terminal, corymbose): Both male and female flowers are found in the same bunches of the herb. Flowers when viewed as a whole, looks like a single flower. 3 to 7 flowered cymes or panicles appearing laterally in the axils of the upper leaves on short, rigid and forked peduncles, Flattened-globose, 1.5-2 mm x 4-5 mm, reddish, prominent in groups of tree, the central one is subsessile, the lateral ones with apeduncle of 6-7 mm, cyathial glands 5 oblong, 1-3 mm broad. Corolla absent but the involucres has two nearly round to ovate, bright red bracts 3-7 mm long. Inflorescence or the arrangement of flowers in a bunch on the plant is cyathium type (one female and several male flowers are found on a same bunch) [12]. Basically, male flowers many, bracts linear while female flowers rarely developed. Flowers and fruits occurs during the month of December to May [4].

Fruits: Fruits (capsules) are three chambered or 3-lobed, smooth, stigmas slightly dilated and minutely toothed with 10-12 mm in diameter [4].

Latex: Latex is a milky-sap-like fluid found in cells or vessels and usually executed after tissue injuries that make up the laticiferous system [13].

Cultivation Needs: Needs full exposure to the sun but can also succeed to grow in light shade. They prefer rocky areas for the growth. They need well drained soil. Grows well in dry place and rocky area in villages of all over India [15-17]. It needs no maintenance. It is a moderately fast grower, and will quickly become large landscape masterpieces in just 3-5 years. Water regularly during the active growing season (at least weekly) from March toSeptember but no water should ever be allowed to stand around the roots. Keep almost completely dry in winter.

Chemical Constituents

Phytochemical investigations on Euphorbia neriifolia yielded in the isolation of several classes of secondary metabolites, many of which expressed biological activities such as Euphol (8,24- euphadien-3β-ol), monohydroxy triterpenes, nerifoliol, taraxerol, flavonoids, steroidal saponins, sugar, tannins, alkaloids, β-amyrion, glut-5(10)-en-1-one, cycloartenol, 9,9-cylolanost- 20(21)ene-24-ol- 3-one (neriifolione), and triterpenoidal saponin [18,19]. Chemical constituent present in different part of plant: Euphol (Whole plant, bark, latex, root); friedelan-3 and 3β-ol, D:B-friedoolen- 5(10)-en-1-one, glut-5(10)-en-1-one and taraxerol (stem, leaves); n-hexacosanol, euphorbol, hexacosanoate, 12-deoxy-4β- hydroxyphorbol-13-dode-canoate-20-acetate and pelargonidin- 3,5-diglucoside (bark); 24-methylenecycloartenol and tulipanindiglucoside (bark, root); nerifoliol (latex), cycloartenol, euphorbol, ingenol triacetate, 12-deoxyphorbol-13,20-diacetate, delphinidin- 3,5-diglucoside (root) [19-21] (Figures 3 & 4).

Figure 3:

Figure 4:

Latex portion contain 69 – 93.3% water and water soluble and 0.2 – 2.6% caoutchouc [22,23]. The latex of E. neriifolia is an active ingredient of many Ayurvedic formulations like Abhaya lavana, Avittoladi bhasma, Citrakadi taila, Jatyadi varti, Snuhidugdhadi varti, Snuhi ghrta and Jalodarari ras. It (gum resin) was found to contain Euphol, neriifoliol, neriifolene, Euphorbon, Resin, gum, caoutchouc, malate of calcium, monohydroxy triterpene, taraxerol, β-amyrion, glut- 5-(10)-en-1-one, neriifolione and cycloartenol [24].

Fresh latex yields 10.95% solid with 18.32% total resinous matter, and 24.50% and 16.23% of total diterpene and triterpene respectively. A gum resin which is the active principle, traces of an alkaloid; wax, caoutchouc, chlorophyll, resin (2.40%), tannin, sugar, mucilage, calcium oxalate, carbohydrates albuminoids, “gallic acid quercetin, a new phenolic substance and traces of an essential oil”. Neriifolin-S and neriifolin, 9,19-cyclolanost-22(22’),24-diene- 3β-ol (Neriifoliene), 5-eupha-8,24-diaene-3β-ol (Euphol), Neriifoliene and euphol, 9,19-cyclolanost-20 (21)-en-24- ol-3-one (Neriifolione), cycloartenol, Neriifoliol, Lectin, etc are the chemical constituents extracted from fresh [25-29] or dried latex [30,31] of E. neriifolia. The leaves of Euphorbia neriifolia L. were found to be highly fibrous (nearly 15.36%). It may contain suberin or cutin, some amount of carbohydrates, cellulose and lignin. It contains higher amount of calcium oxalate crystals and starch than stem and leaves. It contain high values of total ash, and smaller values of acid insoluble and water soluble ashes. The leaves of Euphorbia neriifolia L. were found to be rich in calcium and potassium [32]. The results of phytochemical screenings of hydro-ethanolic, petroleum ether, benzene, chloroform, ethyl acetate, ethanol and aqueous extracts of leaves mainly revealed the presence of proteins, glycosides, alkaloids, phenolics, flavonoids, saponins and terpenoids in appreciable, moderate and trace amount. The proteins and amino acids were possessed in negligible amount [14].

In one of the study, the hydroalcoholic extract of E. neriifolia was found to contain sugar, tannins, flavonoids, alkaloids, 24-methylene cycloartenol, and triterpennoidal saponins on preliminary phytochemical analysis and there is absence of fixed oils and glycosides. Several triterpenoids like Glut-5-en-3β-ol, Glut-5(10)-en-1-one, taraxerol and β-amyrin have been isolated from the powdered plant, stem and leaves of E. neriifolia. The leaf extracts in the water and organic solvents such as chloroform, ethanol, ethyl acetate, and butanol of E. neriifolia were found phlobotannins, flavonoids, saponins, tannins, terpenoids, phenols and cardenoloids [33,34].

a) Moisture content: Leaf 73.8%, Stem 62.4%, Bark 86.9% Whole plant 78.6 [35]./p>

b) Oil content: Leaf 2.46%, Stem: 3.56%, Bark 4.95%, Whole plant 3.87% [35].

c) Polyphenol content: leaf 4.67%, Stem 9.63% Bark 12.68% Whole plant 11.49% [35].

d) Hydrocarbon content: leaf 0.42%, Stem 2.58%, Bark 2.93, Whole plant 2.28% [35].

Pharmacological Uses

Plants are bitter, laxative, carminative, acrid, pungent, improves appetite, abortifacient, digestive, expectorant, depurative, febrifuge, stomachic, vermifuge, useful in abdominal troubles, bronchitis, tumors, loss of consciousness, asthma, leucoderma, piles, inflammation, enlargement of spleen, anemia, ulcers, cutaneous diseases, dropsy, dyspepsia, pain, flatulence intermittent fever, fever and in chronic respiratory troubles [36-38].

a. The leaves are diuretic. The leaves are heated, squeezed, and the sap taken, sometimes with salt, to treat asthma, wheezing in babies, colds, aphrodisiac, and stomach upset. The leaves are also used to treat fevers, coughs and colds, carminative, stomachic and expectorant, chronic respiratory troubles, bleeding piles and diabetes [34,39,40]. Applied externally, the sap is used to treat infected nails and to relieve earaches. The expressed juice of the leaves is reported as very effectual in relieving the paroxyms of spasmodic asthma. The anti-inflammatory and analgesic activity of hydro alcoholic leaves extract of Euphorbia neriifolia is due to the presence of flavonoids [41].

b. In a study, E. neriifolia leaf extract was found to be a potent analgesic, anti-inflammatory, mild CNS depressant, wound healing activity along with humoral and cell mediated immunostimulating activity [42]. E. neriifolia reduced serum lipid profile and glucose signifying catabolic property with added in vivo and in vitro antioxidant activity.

c. The bark has been used as a strong purgative. The root is considered antiseptic, antispasmodic, purgative and local rubefacient activity [34]. Mixed with black pepper, it is employed in the treatment of snake bites both internally and externally.

d. The latex also reported its oral efficacy and safety on adjuvant arthritis, skin warts, and earache [37]. In a 14-day repeated dose sub-acute toxicity study, the drug showed to possess striking anti-arthritic activity. The white, acrid, milky juice (latex) is internally a purgative and externally it has rubefacient properties. As drastic purgative, it is given in combination with other medicines such as chebulic myrobalan, longpepper, trivrit root and which are kept steeped in it in cases of ascites, anasarca and tympanitis. The latex juice is also applied to remove warts and similar excrescences and to afford relief in earache; mixed with shoot it is used as an anjan in ophthalmia; mixed with margosa oil it is used as an application in rheumatic affections. The juice is largely used with clarified or fresh butter as an application to unhealthy ulcer and scabies and applied to glandular swellings to prevent and suppuration. It is expectorant, pungent and is thus used in treating tumors, arthritis and abdominal pains. Turmeric powder mixed with the milky juice of Euphorbia neriifolia is recommended to be applied to piles. The tribal population of Chattishgarh region uses the milky latex as an ingredient of aphrodisiac mixture [37,43].

e. 0.5% and 1% sterile water soluble fraction of E. neriifolia latex was evaluated for wound healing activity in guinea pig. E. neriifolia latex showed increase in collagen and DNA content improving the tensile strength. It also showed increased epithelization and angiogenesis indicating potential wound healing property [7,44]. There is report of its anti-inflammatory and antiarthritic activity of a novel triterpene (Nerifolione) isolated from the latex of E. neriifolia along with total extract of latex in acetone.

f. Antibacterial effect was found of the leaf extract of E.neriifolia in the ethanol and chloroform when was tested against the different bacterial organisms and it was believed to be due to the presence of tannins, phlobatannins, saponin, cadenoids, phenol, terpenoids and flavonoids which have been shown to possess antibacterial properties. The water and ethyl acetate extract exhibited very less activity [31].

g. Analgesic and Anti-inflammatory study had been carried out of the 70% hydroalcoholic leaves extract of E.neiifolia by using tail flick method and the Carrageen induced hind paw edema method, which had led to the confirmation of the analgesic and anti-inflammatory activity of E.neriifolia. The analgesic effect of leaf hydroalcoholic extract was also evaluated using Eddy’s hot plate method in albino rats. It shows significant analgesic and Anti-inflammatory activity as compared to the standard drugs, diclofenac sodium and indomethacin respectively [7,45]. The anti-inflammatory activity of petroleum ether fraction of latex of E.neriifolia is also studied on the rat by paw edema method. The pet. Ether fraction contains triterpenes euphol, nerifoliol and cycloartenol having anti-inflammatory and analgesic activity [7,46].

h. E. neriifolia leaf extract was found to be mild depressant on central nervous system at higher doses. E. neriifolia leaf extract at 400 mg/kg dose potentiates pentobarbitoneinduced duration of sleep. Leaf extract did not have any motor in coordination or ataxia on muscle grip performance in mice effect in rota rod test and showed statistically insignificant reduction in locomotor activity. The elevated plus-maze introduced by Lister for mice is based on the apparent natural aversion of rodent to open and high spaces which forms the basis for its use in the measurement of anxiety as well as short-term memory. E. neriifolia at 400 mg/kg dose exhibited pronounced antianxiety activity by significantly increasing preference to open arm percent number of open arm entries and percent time spent in open arm. The results of the present study showed that the mice spent a significantly higher time in the open arm and also entered them more frequently signifying the anti-anxiety activity.

i. The E. neriifolia leaves extract and isolated flavanoid significantly restored the antioxidant enzyme level in the kidney and exhibited significant dose dependent protective effect against DENA induced nephrotoxicity, which can be mainly attributed to the antioxidant property of the extract. This study paid way for the use of hydroethanolic extract of E. neriifolia as anti-carcinogenic potential and for protection of ENF against DENA induced renal cancer [47]. DENA exposed animals showed alterations in normal hepatic histo-architecture, which comprised of necrosis (N), dilated sinusoids and vacuolization of the cells. Mice treated with E. neriifolia lower (ENL) and higher (ENH) dose and ENF before intoxicated with DENA showed that the liver cells were normal, with very little necrosis. The ENH and ENF protect the hepatic tissue against DENA-induced hepatic carcinoma [48].

j. The extract of E. neriifolia leaves possesses antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant activity of ethanolic extract of E. neriifolia was evaluated by various antioxidant assays such as TAC, FRAP, FTC, TBA and non specific activity. All the result of anti oxidant activities found were compared with standard antioxidants. The highest antioxidant property was found for the ethanolic leaf extract of E. neriifolia [7,49]. The catabolic and antioxidant effect of the extract may be due to presence of saponins and flavanoids [50].

k. The hydro-alcoholic extract of dried leaves of Euphorbia neriifolia possessing significant protection against E.coli induced abdominal sepsis, significant increase in total leucocyte count, differential leucocyte count and phygocytic index were determined. It shows significant activity [51].

l. Different doses of aqueous extract E. neriifolia were administrated to both sex of Wister albino rats along with standard frusemide. The collected urine sample were tested for concentration of Na+ and K+ by flame photometer, the tested samples increases the urine volume as an effective hypermatraemic and hypercholaemic diuretic [7,52].

m. The anti-diabetic and anti-hyperlipidemic activity of ethanolic extract of leaves of E. neriifolia was studied on the type-2 diabetic rats. After 21 days of oral administration of 200 – 400 mg per kg of etanolic extract produced decrease on fasting blood glucose, triglyceride, cholesterol, LDL levels in HFD-STZ induced type-2 diabetic rats, on the other hand there was significant increase in HDL levels. It indicates that the ethanolic extract exhibits anti-diabetic potential along with potent lipid lowering effect after repeated oral administration [53].

n. Psychopharmacological profile of hydroalcoholic extracts of E. neriifolia leaves in mice and rats was studied and the result suggested that the leaf extract significantly reduces apomorphine induced stereotypyin mice at all doses. The result also suggested that, the leaf extract shows antipsychotic, anti antianxiety, anti-convulsant activity in mice and rats [7,54].

o. The hepatoprotective effect of saponin fraction of isolated from the leaf extract of E. neriifolia was studied on CCl4-induced hepatotoxicity on rat. During the study they found that cytosolic enzymes like SGPT, SGOT and ALP elevates in the blood and hepatic glutathione and SOD decreases [55].

Traditional Uses of E. neriifolia [34]

The plant has been used in Ayurveda, Unani and Sidha. A traditional uses of E. neriifolia (Sehund) as per Ayurveda are – to improve digestion strength (deepana); induces server purgation (rechana); useful in treating disorders of veta-dosha imbalance such as neuralgia, paralysis, constipation, bloating, etc; unctuous oily (snigdha); light to digest (leghu); etc [56].

a. The leaf of E. neriifolia is heated and tied over the area affected with pain and inflammation.

b. The fresh juice from the leaf is poured inside the ears to treat earache, to defrost skin warts, and in arthritis. The milk latex of Euphorbia neriifolia is applied over warts as part of treatment.

c. Oil processed from the leaf of E. neriifolia and sesame oil is used for external application to treat joint pain.

d. The paste of the leaf of E. neriifolia is applied over the skin to treat skin diseases.

e. The vaidhyas from ancient times used to use the milky juice exuded from the injured stems as drastic cathartic and to relieve earache. They are used as a drastic purgative in the enlargement of liver and spleen, syphilis, dropsy, general anasarca, leprosy, etc. It has been found beneficial for Asthma [6,34]. The method as found by a Ayurvedic doctor is by the prepared succus consisting of equal parts of the juice of this plant and simple syrup; administered in doses of 10 – 20 drops three times a day; has been found to relieve asthma attacks completely.

f. Latex is acrid, laxative, pungent and good for tumours, abdominal troubles and leucoderma. It is also used as a purgative, rubefacient, carminative, expectorant, whooping cough, gonorrhoea, dropsy, leprosy, asthma, dyspepsia, jaundice, enlargement of the spleen, colic and stone in the bladder. It is use to remove cutaneous eruptions and warts. It is liable to cause dermatitis [4,15]. The dried juice with some other ingredients used as a drastic purgative in the enlargement of liver and spleen, syphilis, dropsy, general anasarca, leprosy, etc. Juice is largely used with clarified or fresh butter as an application to unhealthy ulcers and scabies i.e. it is used for cleansing the abdomen in cases of poisoning and in severe constipation. When applied to glandular swellings it prevents suppuration. Mixed with Margosa oil it is applied to rheumatic limbs. The fresh milk latex of Euphorbia neriifolia is used in the preparation of ‘Kshara sutra’, applied for the medicated thread useful to treat piles and fistula or over external pile mass to reduce it. Turmeric powder mixed with the juice of Euphorbia neriifolia is recommended to be applied on piles. Thread steeped in the above mentioned mixture is used in ligaturing external Haemorrhoids [6,34]. Normally, as found by the survey, Asthma patients take the latex by mixing it with honey. Juice mixed with ghee is given in syphilis, in visceral obstructions and in spleen and liver enlargements due to long continued intermittent fevers. Externally the juice is applied to remove warts.

g. Root- bark boiled in rice-water and arrack is given in dropsy [6,34,57]. Root and stem is used as symptomatic treatment of snake bite, scorpion sting and as a antispasmodic. Root and milky juice mixed with black-pepper is employed in scorpion- stings and snake bites, both internally and externally but large dose causes irradiation and determatitis. The stem is roasted in ashes and the expressed juice with honey and borax is given in small doses to promote expectoration of phlegm and juice from fresh stem of E. neriifolia is added with honey and borax to treat cough and sore throat. Pulp of the stem mixed with fresh ginger is used to prevent hydrophobia [57].

h. Euphorbia is used for breathing disorders including asthma, bronchitis, and chest congestion. It is also used for mucus in the nose and throat, throat spasms, hay fever, piles, and tumors. Some people use it to cause vomiting. In India, it is also used for treating worms, severe diarrhea (dysentery), gonorrhea, and digestive problems [4].

i. The tribal population of Chhattisgarh region uses the milky latex as an ingredient of aphrodisiac mixture [7]. The juice of the plant is used in Gujarat for smearing cuts made by tapers on Borassus flabellifer (Linn) in order to prevent the palm from the attack of red weevil. Stem or leaf juice is used in case of cough and cold mixed with honey [58].

j. E. neriifolia latex is one of the constituents of “Kshaarasootra”, which is used in Indian medicine to heal analfistula. A multicentric randomized controlled trial carried out by Indian Council of Medical Research revealed that the long term out come with “Kshaarasootra” was better than with the surgery offering an effective, ambulatory and safe treatment for patients with fistula-in-ano [59].

k. Euphorbia neriifolia Plant used in different Ayurvedic medicines, some of them are listed here – Agnivrana Taila (for burns, boils, etc), Ayaskirti (for anemia, weight loss therapy, skin diseases, etc), Vishatinduka taila (for gout, numbness, skin diseases), Abhaya lavana (for liver and spleen disorder), Madhusnuhi rasayana (for skin diseases like eczema, psoriasis, diabetics, carbuncles, piles, tumors, goiter, iching, rheumatoid arthritis, etc), Shanka dravaka (for ascites, indigestion, liver and spleen diseases), etc.

Harmful Effects

The latex portion of the plant is actually regarded as the toxic part in the plant [10].

a. The plant is poisonous and skin contact with the sap can cause blistering: The milky latex or sap of Euphorbia species is found to be toxic and may cause intense inflammation of the skin and the eye. Ocular toxic reaction ranges from mild conjunctivitis to severe kerato-uveitis. Corneal involvement generally follows a typical sequence with worsening of edema with epithelial sloughing on the second day. It is believed that some species are more toxic than the others. Few cases have also been reported about the permanent blindness occurring due to the accidental inoculation of the Euphorbia neriifolialatex. When treated early and managed meticulously, the inflammation generally resolves without sequelae [60].

b. The leaves and roots is used as a fish poison [60].

c. The injection of the latex causes Irritation, Vomiting, Diarrhoea, Burning sensation in the abdomen, Convulsions and Coma. On contact with the skin there will be Burning of skin and vesication [61].

d. There will be Inflammation of eye and temporally Blindness if the milk of plant falls to the eye. Treatment for the person who has been come in contact with the latex can be washing the contact part with running water. It holds good even for the contact with the eyes [54].

The symptomatic treatment includes [12]:

a. On ingestion: Gastric lavage is recommended with normal saline or Activated charcoal.

b. On contact: with the skin – Topical corticosteroids are used, with Eye- Antibiotic eye drops, Tears substitute, IOP (Intra ocular pressure) lowering medications.

The post mortem investigation showed the Signs of inflammation of contact part, gangrenous patches in the stomach and rotten spleen. The medico-legal importance includes accidental poisoning, Homicidal and suicidal purposes, which are very rare and used for procuring criminal abortions [12].

Conclusion

Utilization of plants for medicinal purposes in India has been documented long back in ancient literature because they are essential for human survival. Traditional medicinal system is widely distributed in India. A major proportion of population mostly belonging to rural areas is still dependent on traditional system of medicines for their various health needs. Therefore, traditional and cultural medical knowledge has a catalyzing effect in meeting health care demands. From the available literature survey, it should clearly show that Euphorbia neriifolia L. serve as an important source of many therapeutic efficient chemicals. It is extensively used in an Indian medicine system in combination with other plants and natural products. This plant is useful in abdominal troubles, bronchitis, tumors, loss of consciousness, asthma, leucoderma, piles, inflammation, enlargement of spleen, anemia, ulcers, cutaneous diseases, dropsy, dyspepsia, pain, flatulence intermittent fever, fever and in chronic respiratory troubles due to present of different natural products as Euphol, monohydroxy triterpenes, nerifoliol, taraxerol, flavonoids, steroidal saponins, sugar, tannins, alkaloids, β-amyrion, proteins, glycosides, alkaloids, phenolics in appreciable, moderate and trace amount. This is one plant has been successfully used in many health problem since a long period of time for the treatment of wide variety of health issues. There is scope for developing newer drug molecule or mixture for the treatment of multiple diseases only by changing the dosage. The Euphorbia neriifolia L. is poisonous and skin contact with the sap can causes blistering.

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Ceramic Dental Implants: A Literature Review

Abstract

Background: Titanium, also known as conventional implant is the gold standard material for dental implant. The reason behind this is their outstanding biocompatibility, adequate mechanical properties and beneficial results. When exposed to air, titanium instantly develops a stable oxide layer, which forms the basis of its biocompatibility leading to a better Osseointegration [1-3]. Zirconia (ZrO2) is a ceramic material with sufficient mechanical properties for manufacturing of medical devices [2] Zirconia-based implants were introduced into dental implantology as a substitute to titanium implants. Zirconia seems like an appropriate candidate for implant material due to its tooth-like color, its biocompatibility and its mechanical properties and low plaque affinity [1,4] The major drawback of titanium is its gray color. In various situations, there could be an unaesthetic display of the metal components due to lack of soft tissue height over the implant level this can also take place following soft tissue recession and marginal bone loss [4,5]. Zirconia opacity is very helpful in unfavorable clinical situations. Radio- Opacity can aid evaluation during radiographic controls. Frameworks of Zirconia are made using computer-aided design/manufacturing (CAD/ CAM) technology [5].

Aims of this Study: The aim of this study is to review clinical and research articles conducted on zirconia dental implants, observe their success rate with a minimum follow up of 5years & compare them with titanium dental implants.

Materials and Methods: A literature search was performed of the Pub Med database using the following key words: ‘zirconia,’ ‘zirconia implant,’ ‘zirconia versus titanium. The searches were limited to articles in English published from 2003 to 2016.

Results: A total of 4 articles matched the criteria of a minimum 5year follow up study. A cumulative success rate of 92.2% was observed.

Conclusion: Literature search showed that the success and longevity of dental implants strongly depend on surface characteristics and adequate osseointegration. And that the use of right size, shape, length and diameter of the implant in optimal loading conditions would increase the chances of successful implant placement. Although it also highly depends on that the right technique is being followed by the operator. Some of the properties of zirconia seem to be suitable for making it an ideal dental implant, such as biocompatibility, osseointegration, favorable soft tissue response and aesthetics due to light transmission and its color. Zirconia can prove a feasible alternative in replacing titanium. A need for more clinical trials concerning resistance to failure in long-term is of high importance.

Key words: Zirconia; Zirconia implant; Zirconia versus titanium

Introduction

Dentists and dental specialists use significant clinical skills in an attempt to deal with the consequences of complete and/or partial edentulism [6]. The therapy of completely and partially edentulous patients with dental implants is an accepted and eminent treatment modality [2]. Zirconia is one of the most capable restorative biomaterial, due to its highly positive mechanical and chemical properties appropriate for medical application. Zirconia ceramics (ZrO2) are becoming a widespread biomaterial in dentistry and dental implantology [2]. Titanium has been the preference for dental implants for the past many years. Its properties and characteristics have been found to be most fitting for the success of implant treatment. But lately, zirconia is gradually rising as one of the materials to reinstate the gold standard of dental implant, i.e., titanium [1]. Dental implants are biocompatible metal anchors surgically placed in the jaw bone beneath the gums to hold an artificial crown where natural teeth are missing.

Using the root form implants which are the nearest in shape and size to the natural tooth root, the non-union bone healing stage generally varies from three months to six or more. During this period, osseointegration occurs. The strong sustainability of the implant is due to the bone growing in and around it, to which a superstructure will be attached later on by either cementation or screw-tightening retaining technique [7,8]. Since the material composition and the surface topography of the implants play a fundamental part in osseointegration, various chemical and physical surface modifications have been developed in order to decrease thetime of osseous healing, and it was observed that increased surface roughness of dental implants lead to greater bone apposition and reduced healing time [9].

Review of Literature

Implants are traceable to ancient Egyptian and south American civilization around 1000AD [10]. Where carved seashells and/or stones were placed into human jaw bone to replace missing teeth [11]. With the 18th century being the start of Endosseous oral implantology [10]. The modern dental implant history as we know it started during World War II when in the years of service in the army, Dr. Norman Goldberg thought about dental restoration using metals that were used to replace other parts of the body. Later on in 1948, in association with Dr. Aaron Gershkoff, they produced the first successful sub-periosteal implant. This success formed the foundation of implant dentistry in which they were pioneers in teaching techniques in dental schools and dental societies around the world [10]. One of the most significant developments in dental implantology occurred in 1957, when a Swedish orthopedic surgeon by the name of Per-Ingvar Brånemark began studying bone healing and regeneration and discovered that bone could grow in proximity with the titanium (Ti), and that it could effectively be adhered to the metal without being rejected. Therefore, Brånemark called this phenomenon ‘osseointegration’, and he carried out many further studies using both animal and human subjects [12,13]. The development of modern ceramics started in 1992; and from that time on, dental implant companies have incorporated ceramic surface treatments and ceramic-like elements to implants with the purpose of further enhancing Osseointegration [10].

What Are Ceramic Implants

All-ceramic dental implants were introduced in dental implantology as a substitute to titanium implants. One of the main reasons to find an alternative material to titanium was sensibilization; it is the possible release of metallic ions, and allergy to this material, as reported in some studies [5]. The first ceramic material that was used in the past for dental implants was aluminium oxide. This material showed good osseointegration but it did not have sufficient mechanical properties for long-term loading [5]. More recently, new generation ceramic materials such as zirconia were introduced. Zirconia is characterized by more favorable mechanical properties (high flexural strength (900- 1200Mpa), hardness (1200Vickers), and Weibull modulus [13- 15] than aluminium oxide. In addition, this biomaterial has a high biocompatibility and low plaque adhesion [14,16]. Zirconia exists in three phases, Monoclinic (M), Cubic (C) and Tetragonal (T), depending on temperature. M-phase is fragile at room temperature, and therefore requires stabilization to prevent Tetragonal (T)-to- Monoclinic(M) phase transformation in technical applications. A stress-induced transformation toughening mechanism improves the mechanical strength of zirconia, rendering it more suitable as a dental implant material.

Yttria (Y2O3) is used as a general stabilizer for maintaining the T-phase of zro2. Y2O3-stabilized tetragonal zirconia polycrystals (Y-TZP) have high strength, toughness, and biocompatibility, and elicit biological responses that are similar to those induced by titanium. Therefore, Y-TZP is considered as a potential titanium alternative [11,17]. One unique feature of zirconia is its crack resistance, also called transformation toughening. This phenomenon increases the fracture toughness of the material and might be the explanation for the so far excellent clinical survival rates. Besides sound survival rates, the goal of an implant treatment is to achieve a harmonious reconstruction that cannot be distinguished from natural teeth by the naked eye. This is of particular importance in the challenging and most exposed anterior region of the jaws. The type of zirconia used in dentistry is partially stabilized tetragonal zirconia poly-crystals. This specific type of zirconia exhibits very high fracture toughness, i.e. Resistance towards crack propagation, through a phenomenon called “transformation toughening” [18].

Materials and Methods

A literature search was performed of the Pub Med database using the following key words: ‘zirconia,’ ‘zirconia implant,’,’zirconia versus titanium’. The searches were limited to articles in English published from 2003 to 2016.

Results

Table 1 shows only 4 articles that matched the criteria of minimum 5-year follow up. With a total of 1055 implants inserted to 82 of them failing. This gave us a cumulative success rate of 92.2%. Other result is the comparison of Titanium and Ceramics. The Table 2 shows the differences between them. Zirconia comes as a one piece, with the implant and abutment fused together being easier to maintain. Titanium can come either one piece or two piece, with implant and the abutment separately but harder to maintain. The microgap between implant and abutment in two piece may cause plaque accumulation. The margins of Zirconia and Titanium are at the gingival level and bone level respectively. Titanium can undergo corrosion and might cause allergic reactions. Surface roughness of Zirconia is smooth with less osteointegration compared to titanium due to it having a rough surface.

Table 1: Success Rate with minimum 5 year follow up.

Table 2: Comparison between Zirconia and Titanium.

Discussion

Success Of Implants

The success and longevity of dental implants are strongly governed by surface characteristics. There are certain factors that successful implants must possess to accommodate the ossteointegation. They are:

a. Biological compatibility not to be toxic to surrounding hard and soft tissues,

B. Grassi [22] observed that implants failed after immediate loading

C. Roehling [2] were conducting a research with different implant diameters (3.00mm, 4.00mm, 5.00mm).

They observed that the implants with 3.00mm had. Absence of signs of marginal bone loss around implants surface indicates maintained integration between the implant fixture and the surrounding bone [16]. However, the finding of periimplant bone remodelling must be carefully considered because the marginal bone loss which may be detected around implants after beginning of function should be distinguished from the bone loss that is affected by one or more of the following factors:

a) Traumatic surgical technique,

b) Excessive loading conditions,

c) Location, shape, and size of the implant abutment microgap and its microbial contamination,

d) Biologic width and soft tissue considerations,

e) Periimplant inflammatory infiltrate,

f) Implant and prosthetic components micromovements,

g) Repeated screwing and unscrewing [10].

Other Possible Reasons of Failure

Systemic risk factors can increase the risk of treatment failure or complications, but very few absolute contraindications to dental implant treatment are defined. Conditions that increase the risk of failure include but are not limited to smoking and endocrine disease (tooth and implant loss related to vasoconstriction and tissue hypoxia), osteoporosis (reduction in alveolar bone density and mass due to the altered bone metabolism), microbial and immune-inflammatory factors, cardiovascular disease, myocardial infarction, cerebrovascular accident, severe bleeding issues, and chemotherapy In general, these failure rates have been associated with poor bone quality and/or quantity which leads to poor anchorage and stability of the implant [10,21].

a) Implants failed if the width of the attached gingival is ≤ 2 mm. Other studies have shown that a thin or absent masticatory gingival was associated with bleeding on probing and a significantly greater mean loss of alveolar bone [22].

b) Silk sutures were less likely to support bacterial colonization than other suture materials which minimizes thechance of odontogenic infections.Use of polyglactin 910 was associated with a higher incidence of early loss of implants [22].

c) Smoking can inhibit blood flow to the bone may lead to disrupted Osseointegration [22].

d) A non-infectious process resulting in bone resorption, for which the term “aseptic loosening” is used [17].

i. Titanium

Titanium has a good record of being used successfully as an implant material and this success with titanium implants is credited to its excellent biocompatibility due to the formation of stable oxide layer on its surface [19,23]. The commercially pure titanium (cpti) is classified into 4 grades which differ in their oxygen content. Grade 4 is having the most (0.4%) and grade 1 the least (0.18%) oxygen content. The mechanical differences that exist between the different grades of cpti is primarily because of the contaminants that are present in minute quantities. Iron is added for corrosion resistance and aluminum is added for increased strength and decreased density, while vanadium acts as an aluminum scavenger to prevent corrosion.. Because of the high passivity, controlled thickness, rapid formation, ability to repair itself instantaneously if damaged, resistance to chemical attack, catalytic activity for a number of chemical reactions, and modulus of elasticity compatible with that of bone o, Ti is the material of choice for intraosseous applications [11].

ii. Zirconia

Zirconia was used for dental prosthetic surgery with endosseous implants in early nineties. Ceramic implants were introduced for osseointegration, less plaque accumulation resulting in improvement of the soft tissue management, and aesthetic consideration as an alternative to titanium implants. Apart from there being the esthetic issue due to gray color of titanium which becomes more prominent when the soft tissue condition is not optimal and it becoming visible through the mucosa [11] It may also cause a greyish discoloration of the peri-implant mucosa where as Ceramic abutments are reported to reduce soft tissue shadowing due to their color and enhanced translucency which may lead to optimal esthetic results in combination with all-ceramic crowns [18]. Plaque accumulation and bacterial colonization on titanium is also one of the bigger drawbacks [24-34].

Conclusion

Literature search showed that the success and longevity of dental implants strongly depend on surface characteristics and adequate osseointegration. And that the use of right size, shape, length and diameter of the implant in optimal loading conditions would increase the chances of successful implant placement. Although it also highly depends on that the right technique is being followed by the operator. Many of the properties of zirconia seem to be suitable for making it an ideal dental implant, such as biocompatibility, osseointegration, favourable soft tissue response and aesthetics due to light transmission and its color. Zirconia could be a feasible alternative in replacing titanium. A need for more clinical trials concerning resistance to failure in long-term is of high importance.

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Bacterial Infection of Spine Instrumentation and Microbial Influenced Corrosion (MIC): Chicken or Egg

Opinion

There is evidence that microbes including bacteria and macrophages are associated with in the presence biomedical alloys implants for orthopedic procedures [1-4]. The corrosion of metal alloys (A316L Surgical stainless steel; ASTM F136 ELI Ti6Al4V; ASTM F75/F1537/F799 CoCrMoC) in-vivo has also been well documented [5-8]. Proprionibacterium acnes as well as Staphylococcus Epidermis are considered sulfur reducing bacteria in the petroleum industry and have been found in petroleum stockpiles and pipelines [9,10]. These bacteria are associated with pipeline corrosion in oil fields and refineries [9]. In our own clinical experiences, we have noted a large number of spine metallosis cases and believe that the corrosion of implants and surgical site infections with P. acnes bacteria, or other sulfur reducing bacteria, are intimately connected in revisions and clinical infections. In our practice we observed an association between infection and implant corrosion leading to the initiation of a study examining revision of spinal instrumentation and patient outcomes. In patients who underwent spine instrumentation revision, who had grey or black stained tissues taken for culture in the OR and subsequent to the revision, we found 4 of 10 having P. acnes and Staph. epidermis present as a latent infection. A few patients showed clinical signs of infection, requiring subsequent drains and wash-out to clear all presence of bacteria. As early as 1999, P. acnes and Staph spp. were shown to be associated with orthopedic infections, where it was detected in 63% of sonicated samples taken from 120 patients receiving total hip revision [4]. As recently as 2016, P. acnes were highlighted as a possible contributor to post operative infections in orthopedic procedures [1]. These commensal skin dwelling microbes are anaerobic, sulfur reducing bacteria [11-13]. P. acnes, Staph. aureus and epidermis have been isolated as biofilm forming bacteria in orthopedics as well [3].

What this suggests is the presence of the implant provides a suitable substrate upon which the bacteria can colonize leading to latent infection. Additionally, the bacteria utilize the elements present in the instrumentation to sustain their metabolism while corroding the alloys. The presence of sulfur reducing bacteria and their biofilm formation on metals has been extensively studied in the petroleum industry. As noted, these bacteria are also found in other environments beyond our skin. Zhu et al. [9] identified Propionibacterium sp. strain V07/12348 and Propionibacterium sp. strain WJ6 and even E. coli in natural gas pipelines. Yoshida et al. [10] indentified P. acnes in crude oil samples in Japanese stockpiles as well as Staph sp. The crude tested included supplies from Arabia and Russia. The presence of Proprionibacterium sp. and staphylococci sp. would not be unexpected given the sulfur content of these supplies are 1-2wt%. Conversely, sulfur reducing bacteria have been shown to be capable of residing upon and attacking titanium [14], as well as carbon steels [15]. This attack takes the form of acids such as H2S and proprionic acid created as the bacteria utilize sulfate, nitrate, nitrite, carbon dioxide, Fe3+, Mn4+, Cr6+, and other metal ions or bacterial waste products as electron acceptors for metabolism [16].

Thus, given the ubiquitous nature of these bacteria on the skin and deep dermal layers it is not surprising that latent infections can occur when implanted metal instrumentation is utilized in orthopedic procedures given they provide both a scaffold in the form of a place for biofilm to form and nutrients. Current explanations pertaining to the corrosion of spine biomedical alloys are focused upon galvanic/pitting/crevice, fretting corrosion. Galvanic corrosion of biomedical alloys, specifically Ti6Al4V (ASTM F-136ELI) and CoCrMoC (ASTM F75 and ASTM F1537) is not a real concern in modular constructs where theses two alloys are in intimate contact [5,6]. This is a well-studied phenomenon in spine instrumentation where the mixing of alloys is common, e.g. Ti6Al4V pedicle screw with a CoCrMoC tulip and an interlocking Ti6Al4V or CoCrMoC spine rod [17]. In galvanic corrosion, there are no apparent reactive pathways between Ti6Al4V and CoCrMoC. Similar to what is concluded n references 5 and 6, the risk of galvanic corrosion in our experience is minimal based on the very close electronegative nature of the base alloy elements. Therefore, corrosion in instrumentation must be beyond galvanic corrosion. It has been our experience, that the corrosion coupling of Ti6Al4V andCoCrMoC alloys is predominantly a wear function where fretting between parts continuously exposes pristine substrate alloy to the surrounding body fluids (electrolyte), called tribocorrosion [7]. In previous cases, we have observed the presence of particles or elements present on opposing surfaces present on all components, however, this phenomenon only appears to occur where fretting occurs. No intermetallic particles, suggesting some form of galvanic process are present.

All particles observed are oxides, CrxOy, TiOx, VO, MoO, and alumina based on EDS analysis. The physicochemical properties of the category 6 transition metals, Cr, Mo, W, do not allow them to easily form any intermetallics with Ti, Al, or V at low temperatures [18]. The base elements, Co and Ti, are soluble together and can form a compound through the use of arcmelting. Therefore, if one is to consider galvanic corrosion between these two alloys, the primary consideration must be the half-cell reaction releasing metal ions from oxides on either the Ti6Al4V or CoCrMoC surfaces as well as the electro-potential of the pure metal themselves. It is these released metal ions that act as positive charge carriers in the electrolyte. Both oxides are very stable. For example the major oxide Cr2O3 (the only stable form of chromium oxide in air at room temperature) has no reaction for its reduction in the body as that it is done under high temperatures (>1200°C), pressures, or in aluminothermic reactions, e.g. explosive/combustion reactions. From our ongoing research the most likely explanation for the corrosion of alloys in spine is fretting wear and microbial induced corrosion. Each has sufficient energy to disrupt the passive oxides presence, allowing for corrosion of the substrate metals. Infection of comensual organisms is reasonable as these alloys provide a surface for protective biofilm formation and nutrients for bacterial growth.

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Immediate Reduction in Hospital Pharmacy Costs with Intraoperative Restriction of Albumin Administration

Introduction

Albumin has been used for fluid resuscitation in the OR and ICU, since 1940 [1]. Its usage gained prominence based on the classic descriptions of transvascular exchange by Earnest Starling who purported that colloids such as albumin should be more effective at increasing depleted intravascular volume due to their relative vascular membrane impermeability when compared to crystalloids such as saline [2]. It was not until 1998 that a systematic review by the Cochrane Injury Group Albumin Reviewers that the use of albumin for fluid resuscitation came under scrutiny [3]. In this first summary they described a 6 percent increase in mortality (relative risk 1.68, 95% confidence interval 1.28 to 2.23) in patients with hypovolemia, burns, and hypo-albuminemia who received albumin versus other fluids. This scrutiny lead to the landmark Saline versus Albumin Fluid Evaluation (SAFE) study published in the New England Journal of Medicine [4].

The SAFE study was a double blind randomized controlled trial that compared 4 percent albumin to 0.9 percent saline for fluid resuscitation in the ICU for a population of 6997 patients assigned to receive albumin or normal saline. This landmark study showed that when measuring primary outcomes over a 28-day period, albumin had no inherent advantages over saline in terms of mortality, length of stay, dialysis requirement, and mechanical ventilation duration. Moreover, The SAFE study investigators showed with subpopulation analysis that colloid fluid resuscitation was associated with a 19.6 percent increase in mortality in patients suffering from traumatic brain injury (relative risk, 1.88; 95% CI, 1.31 to 2.70; P<0.001)[5].

While critics of the SAFE study have concerns over the limitations of the 28-day observation period, they inevitably conclude the routine use of albumin for fluid resuscitation is not warranted for both the critically ill and for Intraoperative use [6,7]. Literature showing outcome associated benefits of albumin use is sparse and limited to specific patient subpopulations such as patients undergoing coronary artery bypass graft or suffering from septic shock [1,3,4,7,8]. However, these studies are limited in scope only measuring superficial physiological metrics such as hemodynamics or comparing albumin exclusively to other colloids [7,8].

Methods

Tampa General Hospital is a large multispecialty facility of 1080 beds on the west coast of Florida, with major services in trauma, transplant, and specialty surgery for all ages. Average daily surgeries regularly exceed 200 patients in 60 staffing locations. After cost analysis and hospital-wide discussions, a memorandum accepted by the Pharmacy and Therapeutic Committee on September 2016 was circulated throughout the anesthesia department stating all forms of albumin would be removed from department endorsed anesthesia carts and all future requests for albumin were to be made at the pharmacy counter recording the physician name and indication. Following this memo, a series of guidelines were distributed department wide, to describe possible medical indications suggesting use of albumin and allowing for restricted distribution upon request by the Attending Anesthesia Provider. A synopsis of these Indications is described in (Table 1).

Table 1:

Results

The rapid reduction in utilization was well received by providers in all anesthetic locations, as it was heralded and widely discussed weeks prior to implementation. Tracking of utilization and costper month are described in Figure 1, with a monthly summary and a 12 month follow up Table 2. Following restrictions on albumin administration, our institution was able to reduce average monthly albumin costs from $24,372 to $14,338 providing a potential annual savings of $120,000. After the first six months of the initiative, a slight increase in albumin utilization was noted resulting in a lower average monthly cost reduction than projected. This is possibly due to lack of continued monitoring and education, combined with employee turnover. However, this trend should be remedied with implementation of an education program for new employees and increased scrutiny for current employees to curb incorrect usage habits. Quality metrics such as in-hospital mortality, morbidity, and length of stay were not affected (Figure 1) and (Table 2).

Table 2:

Figure 1:

Discussion

With increasing manufacturing costs and lower production volumes, medical grade albumin has become very expensive. These cost increases in combination with the findings of the SAFE study have contributed to an increasing number of hospital initiatives to reduce albumin utilization for fluid resuscitation [7]. One initiative enacted by the University of Maryland Medical Center cardiac surgery intensive care unit was able to produce $45,000 worth of wholesale savings per month with no changes to morbidity or mortality. In this vein, implementation of similar albumin restrictive guidelines hospital wide would produce considerable CDF savings.

Conclusion

The based on the published data, the use of albumin in modern critical care medicine remains controversial. Although albumin supplementation for fluid resuscitation does not increase the relative risk of death or morbidity, it offers no measurable benefits when compared to crystalloids and other colloids. Following implementation of a restriction on albumin administration, our institution was able to reduce average monthly albumin administrations from 646 to 353, translating to a $10,034 decrease in monthly costs. On initial observation there was no difference in clinical outcomes.

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Endometrial sarcoma. Case Report and Review of the Literature

Abstract

Endometrial stromal sarcoma is a rare type of endometrial cancer that is mainly present in older women. There is no specific classification for this type of endometrial cancer and for this reason we use the FIGO classification that is used to stage endometrial type cancers. The main presenting complaint of women with endometrial stromal sarcoma is PV bleeding. Endometrial sarcoma cells are positive for both estrogen and progesterone receptors and have high levels of CD-10 and inhibin. We present a case of a 56 year old lady who came to the RAC due to PMB and scan findings suggesting of endometrial fibroid. Patient undergone a hysteroscopy which shown a large polypoid lesion in the posterior uterine wall and a large fibroid tissue lesion in the endometrium, suggesting of endometrial sarcoma. Patient had MRI and discussed in MDT, as per Trust policy and she had a TAH+BSO. The histology confirmed the diagnosis of low gradeendometrial sarcoma.

Introduction

Endometrial uterine sarcoma is a very rare tumour of the uterine cavity. It accounts for 0.2% of the total uterine malignancies. The annual incidence for this disease is 10-12/1.000.000 cases and the mean age is between 42-58 years. Despite being very rare, is an extremely indolent malignant tumour with local recurrences and distant metastases even 20 years the initial presentation of the disease:

Cytogenetics

Micci et al. [1] in 2006 identified a specific translocation T(7;17) (p15;q21 with involvement of two zinc finger genes juxtaposed with another zinc finger protein 1 and joint juxtaposed with another Zinc protein 1 was described in most of the ESS. Halbwed et al. [2] study shown a strong correlation between chromosomal deletion on 7p and tumor development and progression.

Pathogenesis

We don’t know the exact pathogenesis of endometrial sarcoma, but PCOS, exposure to tamoxifen and unopposed estrogens, have been implicated in the pathogenesis of uterine sarcoma. WHO in 2003 classified endometrial sarcomas, into:

a) Endometrial stromal nodule,

b) Low-grade endometrial stromal sarcoma and

c) Undifferentiated endometrial or uterine sarcoma

Diagnosis

90% of endometrial sarcomas will present with abnormal uterine bleeding and 70% will be associated with uterine enlargement, too. It is also possible to present with pelvic pain and dysmenorrhea. 25% of individuals will be asymptomatic. Tavasolli et al [3], study shows that in 30 to 50% of cases, by the time of diagnosis, endometrial sarcoma was already spread into neighbor organs. Ganjoei TA et al and Jin Y et al study, shown that, in the majority of cases, endometrial scrapping is useful in the diagnosis of the disease, because it involves both the myometrium and endometrium. Both studies shows that, if the disease is isolated in the myometrium, then endometrial scrapping won’t be helpful. Additionally, due to the fact that, endometrial sarcoma has similarities with the normal endometrium, many times is impossible to put the definitive diagnosis based on the endometrial curettage, and we need to await the histologic diagnosis from the hysterectomy specimen.

Radiology

Ultrasound is not a reliable way to diagnose endometrial sarcoma, because of the similar picture with adenomyosis or uterine leiomyoma. MRI can be useful for the preoperative diagnosis, because it has the advantage to show possible metastases and gives more detailed information regarding the endometrial cavity. The presence of low-signal intensity within the area of myometrialinvasion is suggestive of endometrial sarcoma. Additionally, continuous extension of the lesion into the adjacent structures along vessels, fallopian tubes, ligaments and ovaries is diagnostic of endometrial sarcoma.

Immunohistochemistry

CD10 is a cell surface neutral endopeptidase and Zhu XQ et al. (4), endometrial sarcoma cells express high levels of CD-10 and inhibin expression. Endometrial stromal cell tumors are positive for both estrogen and progesterone receptors

Differential Diagnosis

Endometrial sarcoma should be differentiated from neoplasms with arborizing vasculature, highly cellular leiomyoma, cellular endometrial polyp, low-grade mullarianadenosarcoma, and adenomyosis [5].

Prognostic Factors

Prognosis depends on the staging according to the FIGO classification. In the literature, there are several factor which have been associated with poor prognosis, like increased age, black race, DNA aneuploidy, proliferative activity, expression of hormone receptors, etc. Lai et al study, shown that, older patients (>50 years), black race, advanced stage, lack of primary surgery, nodal metastasis, high mitotic count >5/10 high-power fields, CD10 negative or low expression or even lack of progesterone or estrogen receptors were independent factors for poor survival. However, we do know that, generally endometrial sarcomas have better survival rates than other sarcomas.

Treatment

The following are all potential treatment options for the management of stromal sarcomas:

a. Surgery,

b. Adjuvant therapy

c. Hormone therapy and

d. Radiotherapy.

Surgery is the treatment of choice for endometrial stromal tumors. In case of undifferentiated endometrial sarcomas, patient should undergo debulking surgery for cytoreduction, in order to reduce the potential for metastasis. In case of endometrial stromal sarcomas, patient can undergo only hysterectomy with or without salpingoophorectomy. Because endometrial stromal tumors are hormonally sensitive, post-operative hormone replacement therapy, in case of TAH+BSO, is contraindicated. In case of young patients, we might think to preserve the ovaries, if the case is an endometrial stromal sarcoma type 1, in order to avoid early menopause. Chan JK. Study, shown that 10% of those who underwent lymph node dissection had nodal metastases, and the recommendation was to undergo lympha denectomy for both prognostic, but also for therapeutic purposes. Additionally, patients with positive nodal metastasis had significant poorer prognosis than patients with negative nodes. The results of Chan et al study, supported also by several other studies and for this reason the recommendation is for lymphadenectomy, mainly for prognosis, since the therapeutic benefit, should be proved. Adjuvant therapy, should be considered in stage II-IV endometrial stromal sarcoma and involves hormone therapy with or without tumor dissected radiotherapy.

Hormone therapy is an option in case of endometrial stromal sarcoma, because these tumors have estrogen and progesterone receptors. Hormone therapy include: a) megestrol/medroxyprogesterone, gonadotrophin releasing hormone analogues and aromatase inhibitors, like letrazole and anastrozole. Spano JP et al. [6] and Alkasi et al. [7], are 2 case reports which shows 10 year free survival rate for the patients that received aromatase inhibitor for 10 years. Chu et al. [8], study compared the outcome for the patients who received adjuvant megestrol 160mg/day with those who didn’t. The result was, that patients who received adjuvant megestrol, 75% of them didn’t have recurrence of the disease, whereas, patients who didn’t have adjuvant megestrol, didn’t have recurrence of the disease in 29%. In case of recurrent disease, Maluf FC and Petal S suggest a dose of 2.5mg letrazole daily. Radiotherapy, is an option for the stage II-IV endometrial stromal sarcomas, but not for stage I.

Recurrent Disease

Recurrent disease is possible in 1/3-1/2 of cases and limited in the pelvis and lower genital tract. Distant metastasis can occur after years of disease. Chemotherapy is a mode of therapy for recurrent undifferentiated endometrial sarcoma, there is no strong evidence.

Follow-Up And Survival Rates

The 5 year survival rate for the FIGO type 1 is between 54-100%. The relative 5 year survival rate for FIGO type 2 is 30%, whereas for III-IV is only 10%. Since the recurrence rate is very high with this type of tumor, it is essential to have a very thorough follow-up. It shall be once in 3months for the first year, and half yearly for next 4years. Thereafter, annual follow-up is recommended. The relapse free survival depends on the tumor stage, myometrial invasion, adjuvant therapy, and bilateral salpingo ophorectomy.

Case Report

We present a case of low grade endometrial sarcoma, which corresponds to endometrial stromal sarcoma according to the latest WHO classification (WHO 2003). A 56 year old was referred by her GP to the RAC of NPH due to postmenopausal bleeding PMB). Patient was P6, all normal deliveries and she noticed PMB for 3 days. She is taking amlodipine 5mg OD for hypertension, but otherwise fit and well, She didn’t complain of any allergies and she was updated with the smear tests, which were all normal. She was seen on 15^th of November 2016, at the RAC of NPH by the Gynaecology Oncology lead. She had prior to the clinic (11^th of November 2016) a scan which shown an endometrial thickness of 26mm and a mass in the posterior wall of the uterus, which was typical of a fibroid. In the view of the PMB and the increased endometrial thickness in scan, a malignancy couldn’t be excluded. She was examined by the gynae oncology lead and the findings were: abdomen soft, non-tender, no mass palpated. Speculum examination performed and cervix looked healthy and no obvious cause for PMB was seen. Pipelle attempted,but it was not successful because patient couldn’t tolerate the examination. She was booked for an urgent hysteroscopy (2 week referral) with endometrial biopsy, as per Trust policy. On 28^th of November she had a hysteroscopy. Large polypoid lesion was seen in the lower segment of the uterine cavity. A large fibroid was seen in the endometrium and multiple pieces of this fibroid lesion taken and sent for biopsy via resectoscope. We were unable to completely remove the lesion from the lower uterine segment, since there was a high suspicion of being a cancer and we were afraid not to perforate the uterus and causing dissemination of the disease.

The plan was to send the patient for an MRI and to discuss the case in the MDT meeting. On 29^th of November, she had an MRI of the abdomen-pelvis. The scan shown a soft tissue which was arisen from the endometrial cavity which corresponds to an endometrial polyp and 4.4×4.6cm heterogenous mass from the posterior uterine wall, which is more suggestive of a fibroid or a malignant lesion arising from the myometrium including a sarcomatouslesion . On 29th of November we had the results of histology which shown: low grade endometrial sarcoma. On 2^nd of December we discussed the case in the MDT meeting with the gynae oncology lead in Hammersmith hospital, which is a tertiary referral unit for North West London and the plan was for a total abdominal hysterectomy and bilateral salpingoophorectomy. The histology confirmed the diagnosis of a low grade endometrial stromal sarcoma. As per FIGO classification, the sarcoma was of stage 1B, since the tumor was confined to the myometrium. Microscopically, tumor cells express CD10, SMA, bcl-2 and CD99, but they were negative for desmin, h-caldesmon, melan-A, HMB45, S100 and CD34. We present this case, in order to point the complexity of the case, the rarity and of course, the importance of MDT meeting when you have high suspicion of cancer, without having the histological findings, yet.

Discussion

Endometrial sarcoma is a very rare malignancy of the endometrial cavity and is more frequent in older women. Sarcoma cells have very high hormonal affinity, both estrogenic and progesterone, they have high incidence of recurrence and for this reason follow-up is highly recommended even after the 5 year protocol and the treatment of choice is always total abdominal hysterectomy with bilateral salpingoophorectomy.

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Flapless Dental Implant: Contemporary Trends in Literature Coverage

Abstract

The past decade in medicine it has been established the concept of minimally invasive surgery, consisting in taking advantage of advancements experienced in diagnostic techniques and specific surgical instruments, to perform surgical procedures infringing as less damage as possible to the patient. The present work aims to produce a thorough review of the literature published on the field of Implantology with flapless implant surgery, to determine the current scientific evidence of the technique. After presenting the contemporary trends in literature coverage, we can say that flapless surgeries should be restricted to well-selected cases in which a proper clinical and radiological planning has been made.

Introduction

The cause of the increased initial bone loss within the first year after insertion in not fully understood, and based on data available to date there is evidence that effect of surgical trauma caused by raising a mucroperiosteal flab is a subject of scientific investigation [1-4] The idea that the attendant temporary interruption of the blood supply to the outer layers of the bone could possibly cause increased alveolar ridge resorption [1-5] Maier reported a prospective cohort study for measurement of a mean cumulative crestal bone loss after one year of implant placement with flapped or flapless surgery. It was reported that flapless implant insertion caused less peri-implant loss than implant insertion with flap preparation. Therefore, the flapless procedure represents a protective and promising method in implant surgery [1,6,7] Laleman et al. [8] reported a systemic review for guided implant surgery in the edentulous maxilla, nevertheless, almost all implants included in this review were placed without flaps.

Theoretically, this could have several advantages: the procedure is less time consuming, bleeding is minimal, implant placement is expedited and there is no need to place and remove sutures [8- 10]. Prati et al. [10] reported a 3-year prospective cohort study to evaluate the survival rate and marginal bone loss (MBL) of 132 calcium phosphate-blasted implant inserted by a flap or flapless technique and to study the morhochemical characteristics of the implant surface. It concluded from pratie. Study that flapless and flap technique demonstrated similar results of MBL at the preloading healing period and at the months to 3 years post-loading periods. Both surgical procedures induced an early MBL during the preloading stress-free period. Implant diameter, mandibular/ maxillary location, preloading stress-free period, and smoking habits affect MBL more than the type of surgery after both short and long-term follow-up [9,10].

Hsu et al. [11] reported a study for a comparison of clinical and radiographic outcomes of platform-switched Implants with a rough collar and platform-matched implants with a smooth Collar as one year randomized clinical trial. Our concern in this study is the suggestion of the feasibility and predictability of single implant placement with a flapless approach and an early loading protocol in the esthetic zone [11] The overall implant survival rate was comparable with those seen in previous studies using either the flapless technique or an early loading protocol [12]. With the limitation of Hsu et al study, they concluded the computer-aided flapless surgery in conjunction with an early loading is a feasible and predictable approach, with a 100 % survival rate after 1 year of function in this population, and the flapless approach helped to maintain soft tissue profile in the esthetic region. The mean marginal bone loss was less than 1 mm in both groups, and soft tissue profiles remained stable for up to 1 year of function. Additionally, all patients in both groups expressed high satisfaction [12].

Review of Literature

Pub Med databases were used to search for published articles about flapless implant technique. The search term “flapless implant,” sorted by “publication date “ for the last 5 years was used to capture all relevant articles [13] Additional hand searching was performed to examine five main journals in the field: The International Journal of Maxillofacial Implants, Journal of Oral Implantology, Implant Dentistry, European Journal of Oral Implantology, and Clinical Oral Implant Research. Clinical studies, clinical trial, systemic reviews and case series using this technique were included. Letters to the Editor, animal studies, non-English publications, and unpublished articles were not sought. Some articles were directly excluded after reading only their titles. At this stage there were 42 articles included, and the inclusion and exclusion criteria were defined. These articles were included in introduction and discussion in addition to that, more reviews of literature had been included regarding flapless implant technique.

Main Outcomes of Selected Studies

In recent implant dentistry, computer-assisted surgery (CAS) is becoming more popular and achieves prosthetically driven implant placement [14] CAS was first introduced by Van Steenberghe et al. [ 15,16] The key to computer planning is transferring the planning to the patient using a surgical template that allows placement of the implant directly through the tissue without the reflection of the flap [17-19] Furthermore, immediate restoration is possible because of precise fit, excellent primary stability achieved, and the ability to make a pre-implant model [20] This procedure allows restoratively driven implant placement and restoration to provide a more natural environment for soft tissue formation [21,22]. Nevertheless this approach will be promising future for esthetic zone areas without any intervention for alveolar bone exposure or soft tissue reflection. Recent studies reported identified risk factors for flapless implant surgeries such as type 4 bone, smoking, periodontal disease, the immediate loading only in the flapless group in some studies is a confounding factor, the use of grafts, the use or not use of surgical guides, different prosthetic configurations, and the insertion of implants from different brands and surface treatments [23-26].

Discussion

El Chaar and Castano were conducted a retrospective review of patient records in a single private practice to evaluate the efficacy of immediately placing a novel implant design in posterior jaw locations using a flapless technique [27]. Within the Limitation of this study, it was concluded Implants immediately placed into fresh extraction sites and definitively restored with single-tooth restorations no sooner than 4 months after implant placement achieved survival and success outcomes greater than 95%, which is equivalent to reported outcomes for implant-supported, singletooth restorations subjected to conventional delayed placement and loading protocols. Periodontitis and other co-morbid conditions did not influence the outcome [27[ therefore, the use of flapless implant placement as a “routine” procedure in daily practice need more expertise and professional surgeons, nevertheless during implant surgeries, surgical trauma and patient morbidity should be confined to a minimum [28,29] Overall, to accurately assess the merits of the flapless technique, more studies with similar loading protocols that objectively compare conventional surgery with a flapless approach are needed. Importantly, the available short-term data demonstrate that flapless surgery, initially recommended for novice surgeons, requires more experience and presurgical planning than was originally assumed. Furthermore, this technique is often more demanding than the conventional surgical approach [30]

(Recent studies) Romero-ruiz et al reported different advantages which increase the demand by clinician and patients [31,32]:

a. Faster healing of soft tissue [1].

b. Minimal interference on the blood supply

c. Reduction of bleeding.

d. Reduced surgical time [2].

e. Lower morbidity and an increase on patient comfort [3].

f. High survival rates [33].

Meanwhile, as noted from the revision of the scientific evidence, flapless technique presents certain limitations [34]:

A. A blind technique which lead to the lack of flap reflection and the small diameter of mucous openness make a minimal surgery field exist, thus the vision is very limited, being hindered the correct view of cortical, the form of the crest or the concavities. This will ease the arising of complications such as fenestration of cortical, bad implant placing and its bad angulation.

B. Risk of damaging anatomic structures.

C. Difficulty of keratinized gum which is lack of keratinized gum does not influence on the success of implants in the long term, the currently most-followed trend is that, although it is not essential, the failure rates are higher when there is little or no keratinized gum around the implant [5].

D. Impossibility of flap handling for aesthetic reasons which explain, not lifting a flap and limiting the openness to just a few millimeters, makes very difficult to conduct this periodontal plastic surgery technics to increase the volume of soft tissues buccal to the implant, or improving the situation and volume of the papilla. For this reason, in those cases in which there is little volume of soft tissues it will be better to conduct a conventional surgery for improving the situation of peri-implantary soft tissues [35].

E. Impossibility of evaluating and treating bone defects which leads to low visibility which prevents the correct evaluation of bone crest and determining the existence of irregularities such as dehiscences or fenestrations that may compromise the correct intraosseus placing of the implant [36].

F. For all this, flapless surgeries should be restricted to well-selected cases in which a proper clinical and radiologicalplanning has been made. Patients treated with anticoagulant drugs or medically compromised equally can get benefitted by this minimal invasion technique.

Conclusion

Flapless technique in Implantology falls within the concept of minimally invasive surgery that has been taking prominence throughout last years in different medical disciplines. In Implantology, this technique allows to make intervention with a minimum aggression to both the bone and soft tissues, shortening the surgery time and achieving high levels of satisfaction by the patient. However, the technique is not exempt from complications and limitations; the main obstacle of flapless surgery is the fact of limited visibility of the drilling and during implant placement, so the risk of causing wrong bone directions or damaging neighbor structures is higher than with the conventional technique. The impossibility of performing bone regeneration or soft tissues handling technics would be the other great inconvenience of the technique. For all this, flapless surgeries should be restricted to well-selected cases in which a proper clinical and radiological planning has been made. Patients treated with anticoagulant drugs or medically compromised equally can get benefitted by this minimal invasion technique.

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Effect of Inclusion Rate of Effective Microbes (Em) On Growth Rate of Lambs Fed Low Protein Diet

Abstract

Background: A great majority of animal feed is roughage based (poor in quality) in crop-livestock mixed farming system of southern Ethiopia. EM is considered as one of the options that may improve poor quality feeds dominant in the area. A study was conducted to determine inclusion rate of effective microbes (EM mixed with wheat bran, EM-bokashi) on growth rate of lambs fed low protein diets at Dubo Mante research sub-station.

Materials and Methods: Twenty four (24) post pubertal male sheep of similar age (about 12 months age) with an average weight of 14.1±1.74 kg were purchased from local market. The lambs were assigned randomly to one of the four treatments (T1=0% EM, T2=1% EM, T3=3% EM, T4=5% EM). Water and Rhodes (Chlorias gayana) hay were offered ad libtum.

Result: EM-bokashi supplemented at 5% resulted in significantly (P < 0.05) higher intake and growth rate in terms of weight gain than those supplemented with 3% EM-bokashi. Likewise, lambs supplemented with 3% EM-bokashi showed significantly (P < 0.05) higher growth rate than those supplemented with 1% while the difference between 1% and the control (0%) is not significant. Similarly, lesser disease occurrence was observed in lambs supplemented with EM-bokashi than untreated animals. Supplementing 5% EM-bokashi added 51.2% and 43.6% additional economic incentives over the control and 1% EM level, respectively. Generally, both weight gain and profitability increased as level of EM supplementation advanced.

Conclusion: Additional weight in terms of daily weight gain and profitability considered in this experiment are crucial in the livelihood of small-scale farmers. Hence, 5% EM-bokashi could be recommended as biologically and economically profitable inclusion level for lambs fed on low protein diet under smallholder farmer’s management conditions.

Key words: Lambs; Growth; Roughage; Strategic supplementation; Effective micro-organisms

Abbreviations: BED: Breeding Evaluation and Distribution; SAS: Statistical Analysis System; EM: Effective Microorganisms; CBR: Cost Benefit Ratio

Introduction

Small ruminants are integral components of crop-livestock mixed and serve as investment and insurance due to high fertility, short generation interval and their ability to produce in limited feed resource and their adaptation in harsh environment Tsedeke [1], Deribe et al. [2] Smallholder farmers raise sheep and goats as a major source of meat and immediate cash income in different parts of the country. Despite large number and importance of sheep in the areas, productivity is low due to a number of factors among others feed shortage both in quality and quantity, and health constraints Tibbo et al. [3-5]. The limitation in production due to shortage of feeds and poor nutrition is usually profound in areas where high seasonal dynamics in feed sources, fragile ecologies and environments exposed degradation.

Moreover, a great majority of feeds in crop-livestock mixed farming systems is roughage feeds with low feed values. Improving feeds and nutrition through technologies that improves rumen fermentation of roughage feeds, improves protein supply to micro organisms and reduce methane emission is important to boost the overall productivity, health, and well-being of sheep flocks Woju [6]. In this regard, use of effective microbes (EM-bokashi) for better management of crop residues is thus imperative Safalaoh and Smith [7]. EM is a mixture of groups of organisms that has a reviving effect on the natural environment Daly and Stewart [8] and consists of around 80 species of selected beneficial microorganisms including lactic acid bacteria, yeasts, photosynthetic bacteria, and actinomycetes, among other types of microorganisms such as fungi Xu [9].

The technology of Effective Microorganisms commonly termed (EM Technology) was developed in the 1980’s at the University of the Ryukyus, Okinawa, Japan. The inception of the technology was based on blending a multitude of microbes, and was subsequently refined to include three principal types of organisms commonly found in all ecosystems, namely Lactic Acid bacteria, Yeast Actinomyces and Photosynthetic bacteria Higa [10]. The use of EM in animal husbandry is clearly identified in many parts of the world. A study in Asia where EM was first introduced and is used extensively reported the successful use of EM in poultry and swine units Konoplya and Higa [11] and is added to feed and sprayed for sanitation in these units. Research in South Africa also highlight the potential of using EM for treating pig manure Hankoen et al. [12], which promotes growth of the animals.

According to Yohgzhen and Weijiong [13] and Anon (2002) EM has shown to reduce odour of livestock waste and accelerates conversion into manure compost Yohgzhen and Weijiong [13]. EM as additive improves physiological activity in animals and better feed conversion efficiencies Konoplya and Higa [11]; Safalaoh & Smith [12]. EM prepared mixing with wheat bran (EM-bokashi), creates Probiotics, which increases quantity, availability, digestibility and assimilation of nutrients in animal body. EM equilibrates the micro-flora within the intestines of the animals and consequently improves feed conversion and weight gain due to increased nutrient assimilation. EM reduces production of methane suppresses disease-inducing organisms Higa [10]. In Ethiopia, the assumption that non-conventional supplements such as EM could help reduce high price of concentrates that had been used rumen manipulation and efficient use of fibrous feed materials as., Therefore, this study was designed to inclusion level of EM to be included as an additive in low quality feeds to boost small ruminant production in croplivestock mixed farming systems of southern Ethiopia.

Materials and Methods

Study area Descriptions

The study was conducted at Areka Agricultural research Centre, Mante Dubo experimental sub-station, located at about 305 kms from Addis Ababa and 200 kms from the regional city, Hawassa, through Wolaita soddo road. The station is located at an altitude of 1711 meters above sea level (masl) and situated at N 07’ 06.4312` and E037’ 41.688`. The station has 39 hectares of land, of which about 27 ha is used for grazing. The rainfall of the area is 100-1200 mm with bimodal type of rainfall, the heavy rainy season from July to September while light rainy between March to May. Production of forage such as ‘desho’ (Pennisetum pendicellatum), Napier grass (P. pedicellatum), rhodes grass (Chlorias gayana) and others is commonly produced and distributed for Dorper sheep breeding, evaluation and distribution (BED) site to improve mutton yield of local sheep breeds. There are huge crop leftovers and grass hays produced for livestock feeding during dry season but are poor in quality.

Experimental Animal and Housing Arrangement

Individual pen prepared and partitioned using wooden poles and timber materials. Twenty four (24) post pubertal male lambs of similar age (less than one year) with an average weight of 14.1±1.74 kg were purchased from the local market, Doyogena woreda of southern region. The lambs were kept in quarantine for fifteen days for acclimatization and to monitor their health condition and ensure that they are protected from diseases. Six (6) lambs were assigned for each treatment and grouped (blocked) by their weight and put under each feed treatment. All lambs were dewormed with recommended dose of Albendazole before the trial started.

EM of different treatment level was added as a supplementary feed with a recommended feed intake percentage for small ruminants. Fifteen weeks weight gain data were collected. Feed troughs were made empty 1-2 hours before the next feeding. The basal feed, Rhodes hay (with 85 % DM, 7.13% CP, 70.24% NDF and 60.61% in vitro digestibility) offered ad libtum and lambs were watered twice a day. Three hundred gram of wheat bran (as feed basis mixed EM, EM-bokashi) was offered as a supplement for all experimental animals under each treatment. The treatments were, T1=control (without EM-bokashi), T2= 1% EM-bokashi, T3=3% EM-bokashi and T4=5% EM-bokashi. The supplementation was expected total feed intake (600 gram) as feed basis in the total mixed ration.

Data Collection and Analysis

Weight (initial weight, weekly weight and final weights), health condition and other disease records were collected. Frequency of disease occurrence was analyzed with descriptive statistics. The data were analyzed using General linear Model of Statistical Analysis System (SAS, 2008). Means were separated using Tukey’s test at P < 0.05.

Results and Discussion

There was great variation in weight gain between sheep fed different level of EM-bokashi supplementation. EM-bokashi of 1% supplementation was not significantly (P > 0.05) different from the control (without EM-bokashi supplementation). Lambs fed on 5% EM-bokashi supplementation showed the highest body weight gain as compared to other supplementation levels. The highest level of supplementation (5%) was in line with other literatures done on small stock and poultry. Increasing EM-bokashi supplementation level beyond 5% has not been suggested. The body weight increase with the increasing level of EM-bokashi supplementation in this experiment agrees with other experiments conducted in Debrezeit Agricultural research centre with more level of supplementation in water solution Woju [6] and in Nepal Dahal [14]; Daly et al. [8]. This could be due to improved CP content of the mixture in the 5 % EMbokashi in comparison with other level of supplementation Asfaw [15]; Woju [6] (Table 1).

Table 1: Mean daily weight gain (g/day) of lambs supplemented with EM-bokashi fed on low protein diet.

Six types of disease were diagnosed during the experimental period but no death occurred. Systemic infection was diagnosed on all experimental animals under each treatment group with more frequency under control group (3 times) followed by 1 % EMbokashi (2 times). But it was the same in the other two levels of treatments (3% and 5% EM-bokashi supplementation) (1 time). Pneumonia was diagnosed with equal frequency in the control, 1% and 5% but not in the 3% EM-bokashi supplementation. Orf occurred with similar frequency and duration in all treatment groups on almost all experimental lambs. The lower frequency of occurrence of systemic infection under the two higher level of supplementation may indicate the effect of EM-bokashi on improving health condition of animals Bruchem [16,17]. The result is also in line with the findings of Woju [6] who reported reduced disease and methane emission from EM supplemented animals (Table 2).

Table 2: Mean daily weight gain (g/day) of lambs supplemented with EM-bokashi fed on low protein diet.

Growth Rate

The average initial weight of the lambs used in this experiment was not significant among the treatments (Table 3). At the beginning of the experiment due to adaptation or the depressing role of EM-bokashi, the control was significantly higher compared to treatment effects up until 105 days of age while the final weight of the lambs supplemented with the highest level (5%) of EMbokashi was significantly higher compared with T3. Likewise,sheep treated with T3 had higher final growth rate compared with T2 while the differences between T2 and the control was not significant in the majority of the cases. The results agree with other reports Safalaoh & Smith [12]; Woju [6]. The fact that rumen fermentation improved due to EM supplementation, productivity per unit feed improves under EM supplementation Woju [6] (Table 3).For the first 90 days, lambs fed on diets without of EM-bokashi supplementation were better than those supplemented with EMbokashi (Figure 1). However, when lambs adapted to experimental diets the differences between supplemented and not supplemented become more profound. The results agree with reports of Safalaoh and Smith [7] and Woju [6] (Figure 1).

Table 3: Growth rate of lambs fed low protein diet and supplemented with EM-bokashi.

Means with the different letters (a,b,c) are not significantly different at 5% level of significance; Wt, weight

Figure 1: Trends of weight changes over experimental period of lambs supplemented with effective microbes (EM-bokashi) and fed on low protein diets.

Partial Budget Analysis

Profitability was calculated using Cost Benefit Ratio (CBR). In this economic analysis labour cost incurred for feeding experimental animals during the trial period was not considered as it exaggerates the expense. EM (liquid) used in this experiment was purchased from Woljeejii Agricultural Industry P.L.C and labour cost for bokashi preparation was included in bokashi purchase cost. As it is shown in the table below, 5 % EM-bokashi supplementation is profitable under this experiment. The emerging industrial options globally and in areas where this study conducted are an opportunity to efficiently utilize the technology options Woju [6] (Table 4).

Table 4: Estimation of partial budget for lambs supplemented with EM-bokashi fed on low protein diet.

Conclusion

Small ruminants, particularly sheep, are dependent on hay and crop residues in crop-livestock mixed farming systems. Animals lose weight during the dry season as most of the feeds in this period are poor in quality. Technological options that improve feed intake and rumen digestibility of these bulk feeds is essential to boost productivity. In this experiment, both weight gain and growth rate increased as level of EM-bokashi supplementation increased. Inclusion of EM-bokashi at 5% has also been supported with economic profit. Moreover, the frequency of disease occurrence reduced with increased level of EM-bokashi supplementation. Hence, EM-bokashi supplementation at 5% level is biologically and economically profitable for lambs fed on low protein diet under smallholder farmer’s management conditions.

Acknowledgment

SARI, Southern Agricultural Research Institute, funded this study and is dully acknowledged. Areka Research centre provided facilities and financial support to undertake the experiment.

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Effect of Inter and Intra-Row Spacing on Yield and Yield Components of Lettuce (Lactuca Sativa) in South East Tigray, Ethiopia

Abstract

Development of recommendation on appropriate plant spacing is one of the important agronomic practices to increase the productivity of lettuce. Therefore, a field experiment was conducted to assess the response of Tesfa Mekelle lettuce variety to different inter and intra row spacing in 2014 cropping season at Illala. The experiment was arranged in a factorial combination of three levels of intra row spacing (30, 40 and 50cm) and two levels of inter row spacing (60 and 70 cm) in randomized complete block design (RCBD) with three replications. The result revealed that plant spacing showed significant effects on leaf number per plant, plant width and fresh biomass yield per hectare. Conversely, the treatment combinations did not significantly affect plant height and leaf length. The highest number of leaves per plant was recorded at 50 x 60 cm intra and inters row spacing and the lowest was obtained from 30 x 60cm intra and inters row spacing respectively. The highest biomass yield (53.6 ton ha^-1) was recorded at 40 x 60cm and no further increases was observed when intra spacing increase to 50 cm nor inter row spacing increase up to70cm. The lowest was recorded in spacing 50×70cm. Therefore, it is vital to demonstrate the best treatment (40x60cm) under farmer’s conditions.

Key words: Lactuca Sativa; Inter and intra spacing; Biomass yield

Introduction

Lettuce (Lactuca sativa L.) an annual leafy herb belongs to the family Compositae is one of the most popular salad crops and occupies the largest production area among salad crops in the world. It is popular for its delicate, crispy texture and slightly bitter taste with milky juice as fresh condition. It is the most popular amongst the salad vegetable crops [1]. It is usually used as salad with tomato, carrot, cucumber or other salad vegetable and often served alone or with dressing. Likewise, in Tigray, Lettuce is an important cash and food security crop for small holder farmers and fresh salad retailers. The lettuce which was grown in the region before was early bolting which is nationally released where farmer use traditional way of planting without distinct inter and intra row spacing.

To date a new lettuce variety was released by the Mekelle Agricultural research center. This variety (Tesfa Mekelle) was the first of its kind and its yield and maturity period are higher and longer and tend to form larger leaves which makes it preferred by farmers for commercial purpose. Successful production of any crop however, requires its own agronomic practices among which plant spacing is one of the factors that can affect vegetable quality and quantity. Optimum plant density ensure plants to grow uniformly and properly through efficient utilization of moisture, nutrients and light resulted in maximum yield of lettuce [2]. Nevertheless, information on plant population has been limited for lettuce production particular for the newly released variety. Therefore, this study was initiated with the objective of assessing the effect of different intra and inter-row spacing on growth and yield of the newly released lettuce variety.

Materials and Methods

Description of the Experimental Site: The experiments were carried out at Illala which is geographically located in the south east of Tigray found at elevation of 1970 meters above sea level at 250 5 ‘N Latitude and 390 6 ‘ longitudes. The average minimum and maximum temperature for the aforementioned growing season was 11.1 oC and maximum temperature was 26.5 oC.

Experimental Design and Treatments: The study was conducted in 2014 cropping seasons. The experiment was arranged in a factorial combination of three levels of intra row spacing (30, 40 and 50cm) and two levels of inter row spacing (60 and 70 cm) in randomized complete block design (RCBD) with three replications.

Experimental Procedures: Prior to planting, surface (0-20 cm) soil samples from twelve spots across the experimental field were collected in a zigzag pattern, composted and analyzed at Mekelle soil laboratory research center for pH, texture, soil OC, total N and available P using the standard laboratory procedure to determine the initial soil characteristics of the experimental site. The improved lettuce variety Tesfa mekelle was sown in the nursery and the seedlings were transplanted at 5-6 leaf stage towel prepared beds in the field. Fertilizer was applied at the recommended rate and the field was irrigated every week to meet the water requirement of the crop. All agronomic management practices were done as per the recommendation.

Data Collection and Measurements:

i. Plant Height: The height of the main plant was determined by measuring from the border of the soil to the top of the main plant stem.

ii. Number of Leaf per Plant: It was determined by counting the healthy leaf by selecting four plants randomly from each treatment and average leaf number was taken.

iii. Leaf Width: It was measured by selecting four plants randomly from each treatment and the average leaves width was taken in cm by measuring the width at the middle part of the leaves (at widest part of the leaves)

iv. Fresh Leaf Weight: The average fresh biomass yield was measured by selecting four plants randomly from each treatment by uprooting them from the ground and remove the soil from the root part of plant loose soil and weigh immediately.

Data Analysis: All data were subjected to analysis of variance following statistical procedures of SAS software program version 9.2 (SAS institute, 2003). Whenever treatment effects were significant, the means were separated using the least significant difference (LSD) and LSD fisher procedures at the probability level of( p < 0.05)

Result and Discussions

Soil Physico-Chemical Properties: The selected physicochemical properties of the soil of the experimental site are shown in Table 1. The soil of the study area is Vertisol with a clay texture [3] with a particle size distribution of 40% clay, 35% silt, and 25% sand. High clay content may indicate the better water and nutrient holding capacity of the soil in the experimental site. The soil reaction is slightly neutral according to the rating of Tekalign [4-6], indicating that it is suitable for growing most crops. Based on the limit set by Hazelton and Murphy [7,8], the soil has high CEC. The data further revealed that the soil is low in available P [9] and low in total N content and organic matter [4], indicating that the native nitrogen and phosphorus contents of the soil are inadequate for optimum growth of crops, which also seriously constrains the production of lettuce. Therefore, the soils need fertilizer amendment for successful lettuce production. The soil falls in the category of non-saline soils according to the rating of Hazelton and Murphy [7] (Table 1).

Table 1: Selected physical and chemical properties of the soil of the experimental site, Illala, Tigray./p>

Effect of Inter and Intra Row Spacing On Plant Height and Leaf Length: Data in Table 2 indicated that plant height and leaf length was not significantly influenced by the planting density.

Table 2: The effects of intra and inter row spacing on agronomic trait of lettuce, Illala, Tigray.

Means of the same parameter in a column followed by the same letter are not significantly different at P= 0.05 according to LSD Fishers Protected.

Effect of Inter and Intra Row Spacing On Leaf Number/ Plant: Leaf number responded significantly (P<0.01) to intra and inter row spacing. Leaf number increased as the intra row spacing increased. The highest number of leaves per plant was recorded from 50×60 cm. Increasing intra spacing from 30 to 50 cm significantly increased leaf number per plant. When the inter row spacing was kept constant at 60cm leaf number per plant increased by about 41% and 24% compared to 30cm and 40cm intra row spacing respectively. However, when the interspacing was kept constant at 70cm increasing spacing from 30 to 50 cm did not significantly increased leaf number per plant. This indicates that interspacing beyond 60 cm have no value as the highest is achieved under 60cm inter row spacing treatment.

Effect of Inter and Intra Row Spacing on Leaf Width per Plant: Leaf width of lettuce was significantly (P<0.01) varied in response to plant spacing. The highest leaf width was recorded from the wider spacing (50 x 70 cm) as compared to the closer spacing (30 x60 cm). However, in spite of the highest width total biomass yield was the lowest attributed to the less plant population.

Effect of Inter and Intra Row Spacing on Fresh Yield: Fresh yield of lettuce responded significantly (P<0.01) to the effects of different spacing. Fresh yield of lettuce was the highest (53.6 ton ha-1) in 40×60cm spacing with 23 % yield increment over plants spaced in 30×60 cm and yield decreased further when intra spacing increase to 50x60cm. These results are in agreement with Donald (1963) who also reported that as plant population increases yield also increases proportionally then decreases after it reaches a certain level. The significant increase in fresh yield in response to 40 x 60 cm spacing might be attributed to the optimum plant density per unit area of land. Concomitant with the results of this study, higher yields in response to closer spacing over wider spacing was reported by Moniruzzaman [10,11]. The low yield under 30cm intra spacing could be attributed to less spacing for each plant so the plant does not acquire optimum space for growth due to intra plant competition for light and nutrition. Similar results were reported in carrot Mengistu and Yamoah [12]. Keeping the inter spacing at 70cm and increasing the intra spacing subsequently decreased the biomass yield progressively which might be attributed to insufficient utilization of the growth factors. Hence, the wider spacing 50cm x 70cm gave the lowest yield. These results agree with Firoz et al. [2] who stated that improper plant spacing may cause either too dense or too sparse population resulting in the reduction of lettuce yield [13] (Table 2).

Conclusion

The results of the present study revealed that intra and inter row spacing markedly affected biomass yield, leaf number and leaf width of lettuce. Intra and inter row spacing of 40×60 cm was found to produce highest biomass yield. Keeping inter row spacing at 60cm, intra spacing beyond 40cm decrease yield due to low plant density whilst, intra row spacing below 40cm decrease yield due to plant competition for light, water, nutrition and other growth requirements. Keeping the inter row spacing at 70cm constant all intra row spacing recorded the lowest biomass yield as compared to 60cm inter row spacing at all intra spacing . Therefore, it could be recommended that lettuce plants should be grown in 40×60cm intra and inter row spacing. It is however, suggested to further evaluate the best treatment across a wider range of agro-ecological zones [14-16].

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Correlations Between Degree of Limb Ischemia in MESS (Mangled Extremity Severity Score) Score in Predicting Amputation or Limb Salvage in Crush Injury at Hasan Sadikin Hospital, Bandung

Abstract

Background: Crush injuries to the lower extremities have proven to be a profound challenge to the surgeon. Complex decisions inevitably center about whether to attempt heroic efforts aimed at limb salvage or to proceed with primary amputation. There are many guidance score that can be objectively help surgeons with the decisions. One of them is MESS Score.

Objective: The purpose of this study is to find the correlations between degree of limb ischemia in MESS score component in predicting treatment to Crush lower limb injury patients.

Method: We reviewed the medical record for patients with severe injuries to the lower leg in five years on period of January 2014 to September 2017. The research is a retrospective analytic diagnostic study in 32 patients with 1,7-80,2 range of age (mean=40.95 year old) who suffered from severe lower limb injury. Data was processed based on MESS Score. MESS includes 4 points of observation, which are skeletal& soft tissue injury, degree of limb ischemia, shock, and age.

Result: The limb ischemic time correlates strongly with the surgeon’s decision to treat the crush lower limb injuries. In conclusion, the degree of limb ischemia in MESS score, plays as an important role in determining the treatment on crush lower limb injury patients.

Key words: Crush Injuries; Limb ischemia; Limb salvage; MESS score; Primary amputation

Introduction

Crush injury is an injury to the body that characterized by strong pressure on the upper extremities or the lower extremities which cause damage to bones, muscles, arteries, veins, and/or neurological disorders in areas of the body affected. Crush injury most often affected the lower extremities (74%), followed by the upper extremities (17%), and the remainder involves the body (9%). The most frequent causing of crush injury is traffic accidents. Damage to blood vessels in the crush injury cause ischemia and potentially necrotic in the affected area of the body. Necrotic muscle cannot be repaired anymore, with bone and nerve damage from trauma mechanism, and finally the affected limb cannot be used. Necrosis muscle can release myoglobin which if large amounts can cause myoglobinuria. If not treated, myoglobinuria can cause kidney failure. In addition, bleeding from crush injury can result in hypovolemia, which can lead to shock condition and death [1,2]. Treatment crush injury is a challenge for the surgeon. Assessment level of severity injury, and the consideration to do limb amputation or limb salvaged must be done carefully. To assess whether it needs to do limb amputation, Alan Apley created a criteria for amputation, there are 3 D:

i. Dead: If there is damage to blood vessels, which can be ischemia and necrosis at affected extremity, so that condition can lead to be dead limb and cannot be used.

ii. Dangerous: when injuries occur potentially resulting in death, which usually caused by an infection that spreads and result sepsis.

iii. Damned nuisance: When injuries occur quite heavy so the existence of a broken limb would interfere activity of that person. This is usually caused by continuous pain, severe malformations, recurrent sepsis and loss of limb function.

Criteria established by Apley mainly rely on the subjective assessment of the physician, therefore, Helfet, Howey, Sanders and Johansen makes an objective scoring system to assess crush injury at the affected lower limb, what it can still be saved or to be amputated. The scoring system called the mangled Extremity Severity Score (MESS), which is now widely used around the world. MESS was first introduced to the public in the journal “Limb Salvage Versus Amputation: Preliminary Results of the Mangled Extremity Severity Score”, published in 1990. Helfet stated that the scoring system is a predictor and not a absolute procedure. However, because of the accuracy and the ease of application, MESS is a scoring system that is most widely used around the world to assess the viability of the lower extremities after crush injury.*Point multiply by 2 if ischemia > 6 hours. If the MESS score 6 or less indicates to limb salvaged, while score is 7 or more indicates to limb amputation.

Method

We reviewed the medical record for patients with crush injuries of the lower leg in five years on period of January 2014 to September 2017. The research is a retrospective analytic diagnostic study. Data was processed based on MESS Score. MESS includes 4 points of observation, which are skeletal & soft tissue injury, degree of limb ischemia, shock, and age. Then, we calculate with SPSS. 18 to determine the correlation between MESS Score and the decision, whether limb saving or amputation [3-5].

Results

This research have 32 patients with 1,7– 80,2 range of age (mean =40.95 year old) who suffered from crush lower limb injuries. The result of the study was shown in the Table 1. From the research, there was moderate correlation between degree of limb ischemia in mess (mangled extremity severity score) score in predicting amputation or limb salvage in severe lower limb injury (p=0,00036). We can conclude that the degree of limb ischemia in MESS score, plays as an important role in determining the treatment on crush lower limb injury patients.

Table 1: Mangled Extremity Severity Scoring.

Discussion

MESS score system assesses four variables; there are energy which causing trauma, ischemia, shock and age of the patient. Energy which causing trauma is an indicator of severe crush injury or not. With higher energy, we can estimate that the tissue damage that occurs severe enough and need for amputation. With the worsening of pulsation and capillary refill time of extremity, it shows ischemia on the limb, and may already necrosis. Necrotic tissue cannot be used and potentially lead to sepsis that need to be considered for amputation. In patients with worsening blood pressure showed that cardiovascular disease is caused by crush injury. It can be caused by bleeding or sepsis. Therefore, limb amputation is necessary to be done to handle the causes of shock and save the life of patient. The older a person, the ability to repair damaged tissues is getting low, so when they exposed to an severe injury, the ability to recover is lower than before. Therefore, crush injury in the elderly should be considered to be amputated because it is more difficult to maintain the injured limb. By using MESS Score, we can predict the prognosis of the cases, to determine further action, that need limb salvage or limb amputation can be done carefully, with a score of 6 or less indicates that the limb could still be saved, while if a score of 7 or more shows that need for limb amputation.

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Resection of Giant Hepatocellular Carcinoma: Case Report

Abstract

Huge hepatocellular carcinoma (>10cm) resection it is not frequent in cirrhotic livers due to high mortality rates and poor survival rates. Nevertheless, patients with normal livers have a different prognosis, and can bear until 80% liver resection. This case reports the 60-year-old female patient with abdominal tumor and big in the records of any liver disease. HCC diagnosis was achieved with imaging exams and high blood levels of Alpha-fetoprotein (AFP). Surgical removal was proposed, the left trissegmentectomy. This case shows radical tumor resection the curative treatment.

Key words: Hepatic Neoplasia; Hepatocellular Carcinoma; Hepatectomy; Trissegmentectomy; Hepatic Node

Abbreviations: HCC: Hepatocellular Carcinoma; USG: Ultra Sono Graphy; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; HCC: Hepato Cellular Carcinoma; TACE: Trans Arterial Chemoembolization; AFP: Alpha-Feto Protein

Introduction

Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver, being the fifth most frequent malignant tumor and the third in terms of mortality. Its incidence is estimated to be between 500,000 to 1 million cases a year and is more frequent in tropical countries, underdeveloped or developing. It is more common in males, between the ages of 50 and 60 years, with the ratio of 8:1 in high incidence regions and ranging from 1.5 to 3:1 in regions of low incidence. Its etiology is directly linked to cirrhosis of the liver, as well as to infection by hepatitis virus’s B and C, alcohol consumption, aflatoxin contamination and metabolic diseases, liver being the most important hemochromatosis. HCC has variable clinical presentations, depending on the presence of cirrhosis, typically, degree of tumor liver failure or atypical manifestations and, being more findings Paraneoplastic frequent: weight loss, hepatomegaly, abdominal pain, ascites, jaundice, fever and splenomegaly [1,2]. Laboratory changes arising from the HCC are non-specific and depend on the tumor extension and severity of liver injury. AFP high above 400mg/mL makes the diagnosis; however, 20 to 30% of cases may have normal AFP. Imaging research methods are essential for the diagnosis of the HCC, with the most employees the ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI).

The treatment can be divided into curative: partial resection, liver transplantation, ablative therapies or palliation: TACE, hormone therapy, chemo/radiotherapy, symptomatic and supportive treatment. Despite the cirrhosis is one of the most important risk factors for the development of the HCC, approximately 10 to 15% of cases the liver is normal. Patients without a history of chronic liver disease are rarely diagnosed early, usually are not conducted routine tests for these patients (USG abdomen or dosage of AFP), then the diagnosis is made late, when the patient exhibits symptoms due to large tumor mass. In these cases there is no transplant indication according to the criteria of Milan (single tumor less than or equal to 5 cm, or no more than 3 tumors smaller than 3cm) and non-surgical therapies such as trans arterial chemoembolization (TACE), percutaneous radiofrequency ablation, percutaneous ethanol injection and microwave coagulation therapy have been shown to be ineffective. The only curative treatment in these cases would be resection by more than 60% of patients [3,4].

Case Report

Female patient, 60 years sought the emergency room of Santa Casa de Misericordia de Sao Paulo hospital complaining of abdominal pain and vomiting for 2 months. Pain was diffused throughout the abdominal region accompanied by weight loss of 10kg in 2 months. Concerns have noticed increased abdominal volume, jaundice accompanied by pruritus. Patient was bleached +/4+, her history revealed jaundice +/4+. Flaccid abdomen, painful mass in right hypochondrium palpable until umbilical scar. CT scan (Figure 1) revealed large expansive mass with lobulated margins on the anterior surface of the liver, which featured the heterogeneouscontrast enhancement. Such lesion measured about 17.6 x 18.4 x 14.3 cm, occupied all the left lobe and part of the right lobe of the liver. Also enhanced numerous small vessels within the lesion. There was also other smaller satellite lesions. Gallbladder with homogeneous content and small diffuse parietal thickening. Bile duct dilatation most evident in the left lobe. Small amount of free fluid in pelvic cavity, presence of splenomegaly and aortoiliac iliac atheromatous plaques. In laboratory tests showed increased liver enzymes: alkaline phosphatase of 2231U/L (70-290 U/L), gamma glutamyl transferase of 989U/L (< 38 U/L), TGO of 307U/L (8-33 U/L), TGP of 114 (7-35 U/L), AFP greater than 1000ng/ml (up to 8ng/ml), bilirubin total 12.8mg/dL (0.3-1.2mg/dL), direct bilirubin of 7.4mg/dL (0.3-1.2mg/dL) and indirect bilirubin of 5.4mg/dL (up to 1.0mg/dL).

Figure 1: CT scan showing a large expansive mass with lobulated margins on the anterior surface of the liver and heterogeneous contrast enhancement measuring 17.6 x 18.4 x 14.3cm.

There was then the diagnosis of HCC and surgical treatmentleft trissegmentectomy was proposed. In the inventory of the cavity (Figure 2) was able to see right lobe of the liver of habitual aspect and a tumor of approximately 30cm in diameter in the left lobe, rejecting the whole liver and gall to right side, without diaphragm without implant adhesions peritoneal and without evidence of thrombosis of the portal vein. There was difficulty to access the bifurcation of Portal vein because large tumor growth, being necessary to perform first dissection of hepatic veins with bandage and the left and face liver diaphragmatic detachment. Resection was performed at all left lobe the bloody area covered with biological glue. Hilar lymphadenectomy was performed. In intra operative was necessary to 4units of blood transfusion and infusion of vasoactive drugs. The anatomical and pathological report showed surgical piece (Figure 3) the left lobe, caudate lobe and square lobe weighing and measuring 3052g 21x20x11cm. The cuts had greenish tumor, rounded contours and well delimited by measuring hepatic parenchyma in the adjacent 17x11cm displaying 3 nodes of 0.9 to 3cm of diameter 0.5 to 1cm distant from the lesion and with the same characteristics. It was observed the presence of necrotic foci and microvascular invasion without perineural invasion, surgical resection margin free of neoplasia. All lymph nodes were free of neoplasia. Was observed in trabecular pattern, moderately differentiated (Grade 2) and the pathological staging was T3N0Mx, having confirmation of the diagnosis of Hepatocellular Carcinoma (HCC) by examining- HISTO-Chemistry (positive for antigens: CK7, Hepatocyte and KI67). Patient was transferred to the ICU to vasoactive for 1 day after surgery, where evolved well having high in 2 days to bed in the infirmary, where remained stable, afebrile and without complaints getting high on the 5th day post-op. Currently 22 PO, free of neoplastic disease in outpatient follow-up.

Discussion

According to the Barcelona criteria, the patient would fit in the C stage, tumor larger than 5cm, multinodular with microscopic vascular invasion. Therapeutic approach proposed by this classification scheme would be palliative treatment with TACE, chemotherapy with Sorafenib or symptomatic treatment and supportive, being contraindicated liver resection [1]. These criteria, however, take into consideration only patients with cirrhosis, in which the resections must not exceed 50% of the liver tissue, unlike patients without chronic liver disease, in which resections can reach 80% [5,6]. Despite the unfavorable prognostic factors that usually accompany the HCC (high rates of AFP, vascular invasion, multipletumors), the size of the tumor itself can be used as a parameter for contraindication of resection [7]. Lang et al. [3] compared survival among 1, 3 and 5 years in patients with cirrhotic HCC resection, using factors such as: the presence of hepatitis B and C, the presence of fibrosis, resection greater or less than 50%, multifocal, or tumor size greater than 5 cm , degree of differentiation, TNM classification, among others. Framing the patient in this study, we would observe the following survival rates at 1, 3 and 5 years respectively: patients suffering from viral hepatitis 79, 51 and 35%; without fibrosis, 79, 54, 36%; resection more than 50%, 68, 39, 20%; multifocal tumor, 72, 42, 21%; size greater than 5 cm, 74, 48, 29%; moderately differentiated tumor, 70, 32, 18%; TNM stage IIIA, 65, 39, 29% [4].

In a systematic review conducted by Zhou Y-M et al in 2011, survival rates were observed in 1, 3 and 5 years of 60.7, 34 and 28.6% in patients undergoing resection with tumors larger than 10cm. The study considered the partial hepatectomy as therapeutic method considerably me assist in these patients compared to non-surgical options [8]. Although the patient present 17x11cm tumor, not presented macroscopic vascular invasion, cirrhosis, viral hepatitis, low degree of differentiation or capsular invasion, which represent important factors of poor prognosis, opting for the curative resection. Although the only potential treatments represent dressing for these patients, there are still very few studies concerning the effectiveness of partial liver resection in relation to other therapeutic methods. Data indicate that survival rates in noncirrhotic patients undergoing hepatectomy range from 46 to 76% in 3 years and 26 to 68% in 5 years. Data on disease-free survival are scarce, but suggest rates ranging from 24 to 56% in 5 years [3]. The recurrence of the HCC can result from new development of tumor by underlying disease or metastatic dissemination. In patients with cirrhosis, it is more common for recurrence metastasis of hematogenous dissemination. This indicates that even a more aggressive approach as the total hepatectomy would not be enough to prevent relapse [3,4].

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