TUGAS dari Dr KAMAL BASRI SIREGAR, Sp.B(K) Onk

DISUSUN OLEH :

JOS BRIYAN R. H. SIBARANI (110100302)

PROGRAM PENDIDIKAN PROFESI DOKTER

DEPARTEMEN ILMU BEDAH UMUM

FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA

RSUP HAJI ADAM MALIK

MEDAN

2016

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I. Teori Genetik pada Karsinogenesis Kolorektal oleh Eric R. Fearon dan

Bert Vogelstein 1.1 Tahapan perubahan adenoma menjadi karsinoma – Colorectal cancer development

Kanker kolorektal berkembang dari adenoma menjadi karsinoma melalui

beberapa tahapan yang disertai akumulasi dari sejumlah mutasi genetik dan

epigenetik (Morson 1968; Fearon dan Vogelstein 1990). Mutasi akumulasi bervariasi

dalam kanker keturunan tergantung pada mutasi memulai. Dalam keadaan normal

mereka, gen supresor tumor menghambat proliferasi sel. hambatan pertumbuhan

hilang ketika kedua alel dinonaktifkan dengan mutasi dan / atau perubahan

epigenetik, seperti promotor metilasi yang menghambat ekspresi gen. gen supresor

tumor secara luas sesuai dengan hipotesis Knudson klasik dua hit, di mana inaktivasi

kedua alel diperlukan untuk gen supresor tumor kehilangan fungsi normal mereka

(Knudson 1971). Sebaliknya, proto-onkogen tindakan dengan mempromosikan

proliferasi sel. Mutasi gen ini menyebabkan onkogenik yang abnormal over-ekspresi

atau peningkatan aktivitas dari protein.

Colorectal cancer develops via an adenoma to carcinoma sequence with the

accumulation of a number of genetic and epigenetic mutations (Figure 1-3) (Morson

1968; Fearon and Vogelstein 1990).  The mutations accumulated vary in hereditary

cancer depending on the initiating mutation.  In their normal state, tumour suppressor

genes inhibit cell proliferation.  Growth inhibition is lost when both alleles are

inactivated by mutation and/or epigenetic changes, such as promoter methylation

which stifles expression of the gene.  Tumour suppressor genes broadly conform to

Knudson’s classic two-hit hypothesis, where inactivation of both alleles is required

for tumour suppressor genes to lose their normal function (Knudson 1971).  In

contrast, proto-oncogenes act by promoting cell proliferation.  Mutation of these

genes leads to abnormal oncogenic over-expression or increased activity of the

protein.

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The adenoma-to-carcinoma sequence for colorectal cancer is probably most

commonly initiated by bi-allelic mutation of the APC tumour suppressor

gene.  APC mutations have been found in microadenomas (Otori et al. 1998), the

earliest lesion on the pathway (also called aberrant crypt foci (Roncucci et al. 1991)),

and in ~60-80% of early sporadic adenomas and carcinomas (Cottrell et al. 1992;

Miyoshi et al. 1992; Nakamura et al. 1992).  APC is a key member of the

canonical Wnt signalling pathway, and the key mechanism by which mutation of this

gene contributes to carcinogenesis is by activation of this pathway.  However, further

accumulated mutations in additional genes are required for progression of the early

lesions to cancer.

The adenoma–carcinoma sequence. The initial step in colorectal carcinogenesis is

thought to be the formation of aberrant crypt foci (ACF). Activation of the Wnt

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pathway occurs during this step as a result of inactivating mutations in the APC gene.

Progression to adenoma and carcinoma is usually mediated by activating mutations in

KRAS and loss of TP53 expression, respectively. A subset of advanced adenomas

may progress due to mutations in PIK3CA and loss

of 18q. Reproduced with permission from: Pino MS, Chung DC (2010) The

chromosomal instability pathway (CIN) in colon cancer. Gastroenterology

138(6):2059–2072

It has long been observed that luminal environmental conditions alter from the distal ileum to the rectum, and that these conditions are associated with changes in the physical chemistry of the lumen contents including pH, proportions of short- and branched-chain fatty acids and the products of protein fermentation,32 as well as those of the microbiota. Colorectal bacterial populations are responsible for important aspects of both health (synthesis of micronutrients such as Vitamin K, protection of the intestine from pathogenic species) and disease (inflammatory reactions and production of carcinogenic metabolites). In relatively recent publications, authors have described associations between species of bacteria, such as Streptococcus bovis subtypes,33 and Fusobacterium spp.34 and colorectal neoplasia. Importantly, the composition of the gut microbiota also varies with gender,34 and this may be reflected in the distinct distributions of molecular colorectal carcinoma subtypes seen in male and female subjects. A possible explanation for the bimodal distribution of colorectal carcinoma, we observed is that the contact of the large bowel mucosa with luminal contents may last longer in both extremities of the colon than in the mid-colon.

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Terapi Cairan pada luka bakar

Formula yang terkenal untuk resusitasi cairan adalah formula Parkland :

24 jam pertama.Cairan Kristaloid (Ringer laktat) : 4ml/kgBB/%luka bakar

contohnya pria dengan berat 80 kg dengan luas luka bakar 25 %

membutuhkan cairan : (25) X (80 kg) X (4 ml) = 8000 ml dalam 24 jam

pertama

½ jumlah cairan (4000 ml) diberikan dalam 8 jam

½ jumlah cairan sisanya (4000 ml) diberikan dalam 16 jam berikutnya.

Cara lain adalah cara Evans :

l. Luas luka bakar dalam % x berat badan dalam kg = jumlah NaCl / 24 jam

2. Luas luka bakar dalam % x berat badan dalam kg =jumah plasma / 24 jam

(no 1 dan 2 pengganti cairan yang hilang. Plasma untuk mengganti plasma yang

keluar dari pembuluh dan meningkatkan tekanan osmosis hingga mengurangi

perembesan keluar dan menarik kembali cairan yang telah keluar).

3. 2000 cc Dextrose 5% / 24 jam (untuk mengganti cairan yang hilang akibat

penguapan)

Separuh dari jumlah cairan 1+2+3 diberikan dalam 8 jam pertama, sisanya diberikan

dalam 16 jam berikutnya. Pada hari kedua diberikan setengah jumlah cairan pada hari

pertama. Dan hari ketiga diberikan setengah jumlah cairan hari kedua.

Formula Cairan 24 jam

pertama

Kristaloid Pada 24

jam kedua

Koloid Pada 24 jam

kedua

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Parkland Kristaloid 4 ml /

kg / %LB

20-60% estimate

plasma volume

Pemantauan output

urine 30 ml/jam

Evans Larutan saline 1

ml/kg/%LB, 2000

ml D5W*, dan

koloid 1 ml/ kg /

%LB

50% volume cairan

24 jam pertama +

2000 ml D5W

50% volume cairan 24

jam pertama

Slater Kristaloid 2 L/24

jam + fresh

frozen plasma 75

ml/kg/24 jam

Brooke

(Yowler,

2000)

RL 1.5 ml / kg /

%LB, koloid 0.5

ml / kg/ %LB,

dan 2000 ml

D5W

50% volume cairan

24 jam pertama +

2000 ml D5W

50% volume cairan 24

jam pertama

Modified

Brooke

RL 2 ml / kg /

%LB

MetroHealth

(Cleveland)

RL + 50 mEq

sodium

bicarbonate per

liter, 4 ml / kg /

½ lar. Saline,

pantau output urine

1 U fresh frozen

plasma untuk tiap liter

dari ½ lar. saline yg

digunakan + D5W

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%LB dibutuhkan utk

hipoglikemia.

Monafo

hypertonic

Demling

250 mEq/L saline

pantau output

urine 30 ml/jam,

dextran 40 dalam

lar. saline 2

ml/kg/jam untuk

8 jam, RL pantau

output urine 30

ml/jam, dan fresh

frozen plasma 0.5

ml/jam untuk 18

jam dimulai 8 jam

setelah terbakar.

1/3 lar. Saline,

pantau output urine

Sumber lain

Tabel Resusitasi cairan pada luka bakar dalam 24 jam pertama berdasarkan usia

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Rujukan : Pham T. N., Leopoldo C. C., Nicole S. G. 2008. American Burn Association Practice Guidelines Burn Shock Resuscitation. Journal of Burn Care & Research January/February