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2016年12月5日 星期一

[醫如往常] Senior Clerkship Day 96: Lab Medicine: ERCA mutation

ERCA mutation molecular diagnosis 俞教授

Ovarian cancer 2nd most common
15% familial BRCA1, 2
No hot spot
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BRCAness phenotype
Platinum
PARP inhibitor
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Oraparib 亞洲上市
台灣沒有

Hazard ratio 0.35
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>3000 kinds

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Germline 18%
Somatic 7% both alleles mutation in cancer cells
  • Mutation >50%
  • Wild type homozygous mutations
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Capture-based method (ion torrent)
Long range PCR， 分成十段overlap 10k segments

Singapore也要送臺灣做NGS
台灣可以做tissue, 很先進
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大部分用MiSeq
Illumina 只能用blood, 不能tissue
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Setup of BRCA Database

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Founder mutation
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五階mutation
  1. Pathogenic 用藥很有效
  2. Pathogenic-like
  3. Variant of uncertain genecity 人數最多
  4. Non-pathogenic
  5. Normal-like
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BRCA functional mutation: positive
Other mutation 只能註記有
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之後主流
Immunooncology (IO)
Head and neck, 人數跟lung相當
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IHC Synchronization也是努力的目標
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研究比較有信譽
  • 中科院
  • 浙江
  • 華西
  • 復旦
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協和沒有Protocol
data就出來了
data跟西方一模一樣

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2016年9月27日 星期二

[醫如往常] Senior Clerkship Day 21: Ob/Gyn Preeclampsia

Grand round cases
Hypercoiled cord
Termination
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Beta thalassemia Chromosome 11p15.5
Alpha thalassemia Chromosome16p13.3
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FAP familial adenomatous polyps
APC gene
AD 5q21-22 tumor suppressor gene
Colon cancer average 39 yo
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Double balanced translocation
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楊醫師 禾馨新生院長
Toxemia, preeclampsia 妊娠毒血症
FMH fetal Medicine foundation
Perinatologist: Maternal–fetal medicine (MFM)
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Down syndrome
Ultrasound soft marker (week 11-14)
  • Nuchal translucency related to congenital heart disease
  • Nasal bone
  • Ductus venosus
  • Tricuspid regurgitation in week 8
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NIPS; non invasive Prenatal Testing
cfDNA; Cell free DNA
NIFTY test; Non-invasive fetal trisomy test
NIPT; Non-Invasive Prenatal Testing
NIPD; Non-invasive prenatal diagnosis
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Amniocentesis
0.1% complications
PROM, abortion at week 12
NTUH從古自今兩例產婦死亡 

柯教授診所一個月做一千次
(5000-8000元)
國健局補助5000元
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Microdeletion syndrome

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Preterm labor syndrome
7% before week 37
0.7% before week 30
Check Cervical length at week 18-22
T→Y→V→U shape
<2cm preterm risk↑

Cervical incontinence→do McDonald surgery

Fetal fibronectin (fFN)
Week 22-35 positive 早產機率很高
High negative predictive rate
Negative保證不會早產
99.9% within 1 week
99.5% within 2 weeks
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Preeclampsia
Week 12 早期評估, week 24 晚期評估
Uterine artery PI index > 2.5
High resistance, high risk
隨著週數應該要變小
Low PLGF, High risk

Low dose aspirin, decrease 80% risk
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Preeclampsia戴總醫師
CC: 頭痛，腳腫，血壓高, blurred vision, nocturia
Red flag: blurred vision, headache

Aminocentasis ≥34 yo, 國健局補助, week 16-18
Hypertension 140/90
High degree Hypertension 160/110
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小心中風
Mg neuroperection
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D-dimer, predictive of HELLP syndrome
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Creatinine delay
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Uterine artery Doppler
sFT1
PIGF
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Placental grade 3 >39 week
Calcification

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2016年9月17日 星期六

[醫如往常] Senior Clerkship Day 6: Ob/Gyn Hormones in menstrual cycle

Hormones in menstrual cycle
吳教授
1995台大婦產科升等為婦產部，下轄3科。現在每年收六個R。
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https://zh.wikipedia.org/wiki/File:MenstrualCycle_zh.png

















Estrogen
平時 E2<20 pg/ml 測不到(儀器限制)
Day 13>250 pg/ml
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Progesterone
平時P4<0.05 ng/ml
Ovulation 1~3 ng/ml
Post-ovulation P4>10-20 ng/ml
不孕治療要提高到>20 ng/ml
多卵> 2 ng/ml
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LH(草綠色)
平時濃度太高會延遲排卵
Base line: 3-8 mIU/ml
Day 13.5 peak 50-100 mIU/ml
從nadir到peak約14hr，peak後10hr ovulation
檢測到上升之後，8小時要再測一次

Peak後12hr交配最好

IUI則在peak後40-60分放入semen
(Sperm最多活七天, 通常3-5天)

取卵要在hCG注射後34-36小時內取卵
(E.g. 週六晚上十點打hCG, 周一早上八點取卵)
取出後3-4小時才會成熟，才可做ICSI
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安全期：排卵後一天
次安全期：射精七天後
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FSH(水藍色)
Day 13.5 前後 達到peak 30-50 mIU/ml
  • 年輕人通常在排卵第二天達到peak
  • 老人可以快一天

Day 2 FSH function test

Age
FSH
Normal
<10mIU/ml
(E2<50pg/ml)
Age 40
10mIU/ml
Age 45
15mIU/ml
Age 49
20mIU/ml
Menopause
40mIU/ml
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GA 7 weeks (ovulation 5 weeks)開始分泌ACTH
GA 9 weeks 開始分泌DHEA
E+P可在GA9 weeks 停藥
(E+P很重要，老師至少有5個病人停經後懷孕)

Adrenal
Fetus 製造出DHEA運到placenta轉換成E2
(Fetus沒有3beta-HSD; plancenta沒有CYP17)
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E2太高不易懷孕
E.g.
E2
FSH
A
75
8.5
B
35
8.5
A校正
35
11.5
A不易懷孕，B容易懷孕
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小常識
吳教授小時候住在漁村會補烏魚
動物
一次排卵
烏魚
兩萬顆
豬
10-12
狗
5
虎
2
人
1
人雙胞胎機率1/100
三胞胎機率1/1000
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Primordial Follicle 12-30 um
Class 5 約22顆
Class 8 約1-2顆

卵越大顆越敏感，越容易受到granulosa的inhibin B的FSH抑制影響
所以要打人工FSH維持卵子數量

2004台大世界紀錄72顆
病人常問會不會因為取卵打藥造成提早停經，答案是不會，會提早停經都是體質，本來就會提早停經

Stage
Description
Size
Primordial
Dormant, small, only one layer of flat granulosa cells
Primordial follicles are about 0.03-0.05 mm in diameter.
Primary
Mitotic cells, cuboidal granulosa cells
Almost 0.1 mm in diameter
Secondary
Presence of theca cells, multiple layers of granulosa cells
The follicle is now 0.2 mm in diameter
Early tertiary

The early tertiary follicle is arbitrarily divided into five classes. Class 1 follicles are 0.2 mm in diameter, class 2 about 0.4 mm, class 3 about 0.9 mm, class 4 about 2 mm, and class 5 about 5 mm.
Late tertiary
Fully formed antrum, no further cytodifferentiation, no novel progress
Class 6 follicles are about 10 mm in diameter, class 7 about 16 mm, and class 8 about 20 mm. It is common for non-dominant follicles to grow beyond class 5, but rarely is there more than one class 8 follicle.
Preovulatory
Building growth in estrogen concentration, all other follicles atretic or dead

Ref.

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老師Clerk時的心得
以前大家都在外面先看診所
像是Keratoconjunctivitis
在外面看兩間診所各點藥三天都沒好
就來台大看，然後就好了
是因為台大比較會看嗎?
是因為自然病程本來就是一到兩周
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20年前榮總的預算是台大10倍，會領先台大是正常的
現在榮總預算只有台大2倍，所以會被台大超越
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Infertility主要原因
Fallopian tube 不通
卵子不好
精子不好

最早WHO規定要每ml 5000萬隻精蟲才是好的
1992下修到2000萬
2010下修到1500萬
環境賀爾蒙影響很大

百萬/cc

10-15
IUI
5-10
IVF
<5
ICSI
不過有些國家不管那麼多直接做ICSI
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台灣不孕症醫師約有204名
打廣告
Google 點擊每次5元
最近漲到每次29元
先存一筆錢進去，快用完的時候，Google就會提醒你該交錢了
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沒有RCT的研究是垃圾
兩者族群不同，confounding factor根本沒有修正
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NTUH
一年做一千例人工
其中一百例是捐卵

病人付30萬，給donor 9萬9營養費(有的醫院只給五萬)
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IVF療程
Day
Estrade 2mg
E2 (pg/ml)
Utrogestan
P4 (ng/ml)
3-8
1# bid
120


9-11
2# bid
240


12-

360


2W+2
Implantation



2W+2
4# bid
450-460
25mg IM
10-20
4W+2


50
20-40
…


100
40-80
8W+2
2# bid
810
50mg
70
9W+2
0#
1500


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自然懷孕
Week
E2 (pg/ml)
P4 (ng/ml)
5
2500
25
10
5000
50
20
10000
100
36
20000
(80X 排卵250)
180
(10X 排卵10-20)

OHSS
Week
E2 (pg/ml)
P4 (ng/ml)
5
1000-2000
300-600

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Granulosa tumor, 打針
可能出現
E2<1, P2>300-400

慢性不排卵
LH>FSH, E2會高

停經
FSH>LG, E2低
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古代沒有超音波，用E2監測雙胞胎
因為E2來自胎兒的DHEA
E2掉一半，死一個
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晚上
ACTH↑
DHEA↑
E2/P4 ratio ↑
宮縮↑

所以安胎會在睡前打P4
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只有3位RCT醫師可以繼續開原廠藥
其他醫師不能開
所以就換其他藥開，台廠藥掉到每月一萬顆
Premaren (28成分) 18萬顆/每月
Estramon (10成分) 1萬顆/每月
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RU486 降低懷孕率從8%降到5%
100人吃有95個不會懷孕
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長安東路李木生醫師
是condyloma專家
18天latancy
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射精後五分鐘可以在fallopian tube end發現精子
Uterus 7cm
Fallopian tube 11cm
有液體就可能懷孕
不管hymen在不在

精子平均長度45um
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病患說出現月經
有可能是懷孕中出血
仍要驗孕以策安全
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2016年9月15日 星期四

[醫如往常] Senior Clerkship Day 12: Ob/Gyn 翁醫師PGY觀念

    20160913
    Morning Meeting
    Ovarian cancer seeding
    Ileostomy for stage T4 TX
    Stent 只能放在直線. 15cm 處
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    王醫師
    Endometrial cancer
    Serous p53
    Mucinous Kras
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    Lymph node metastasis
    5% well differentiated
    20% poor differentiated
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    翁醫師PGY觀念
    ECG Poor progression: Ant. AMI
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    Pelvic surgery
    Post op
    Walking within 2 weeks

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    Chemo-man

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    Cataract
    1. DM
    2. Galactosemia
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    大球性貧血megaloblastic anemia
    intrinsic factor: parietal cells in the fundus and body of the stomach
    Haptocorrin (also known as HC, R protein, and transcobalamin I, TCN1), is a glycoprotein secreted by the salivary glands which binds to vitamin B12 Vitamin B12 is acid sensitive and in binding to transcobalamin I it can safely pass through the acidic stomach to the duodenum.In the less acidic environment of the small intestine, pancreatic enzymes digest the glycoprotein carrier and vitamin B12 can then bind to intrinsic factor. This new complex is then absorbed by the epithelial cells (enterocytes) of the ileum. Inside the cells, B12 dissociates once again and binds to another protein, transcobalamin II (TCN2); the new complex can then exit the epithelial cells to be carried to the liver.
    Neurological symptoms: Sensory or motor deficiencies (absent reflexes, diminished vibration or soft touch sensation), subacute combined degeneration of spinal cord, seizures,[11][12][13][14] or even symptoms of dementia[15] and or other psychiatric symptoms may be present.
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    Absorption part
    Duodenum: Vit. B9, Fe
    Ilium: Vit. B12
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    Amiodarone
    Side Effect
    1. Thyrotoxicity
    2. Liver toxicity
    3. Lung toxicity
    4. Skin pigmentation
    5. Corneal deposition
    Lab follow up
    1. TSH, free T4
    2. AST/ALT
    3. CXR
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    Postoperative fever
    the five Ws.
    Wind         POD1-2         the lungs, i.e. pneumonia, aspiration, and pulmonary embolism. Once attributed to atelectasis, but a recent review suggests that is not supported by existing clinical evidence.
    Water         POD3-5(7)         UTI; urinary tract infection, related to indwelling catheter (during surgery or currently i.e. Foley catheter )
    Walking (or VEINS, which then sounds like "Weins")         POD4-6(14)        deep vein thrombosis or pulmonary embolism
    Wound         POD5-7(14)         surgical site infection, which in obstetrics or gynaecology, may refer to the uterus(or womb, sounding like wound).
    Wonder drugs or “What did we do?”         POD7+         drug fever, infections related to intravenous lines or reaction to blood products
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    Post-OP
    1. Vital sign: TPR
    2. Pain control
    3. U/O monitor
    4. Drug amount
    5. Wound: dry, clean, color, what, serosanguinous
    6. Ambulation
    7. Diet
    8. Passing gas, fluid support
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[醫如往常] Senior Clerkship Day 11: Ob/Gyn Cases; 乳房檢查

20160912 Cases
Vaginal bleeding
Hematometra
Endometrial cancer
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Amniotic band syndrome

Vascular ring
The primary symptomatology associated with vascular rings relates to the structures that are encircled by the ring, chiefly the trachea, and esophagus. Prompt diagnosis and treatment of these congenital abnormalities can be lifesaving.

Uterine atony
TAE uterine artery
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Edward syndrome Trisomy 18
1/3000
  • Clenched hands
  • CHD, CHD, USA,
  • Mental retardation
  • rocker bottom foot (congenital vertical talus)
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TOCC長灘島
Placenta previa
Vaginal bleeding
Antepartum hemorrhage
UTI

Dengue shock syndrome
Ddx HELLP syndrome
HELLP syndrome is a life-threatening obstetric complication usually considered to be a variant or complication of pre-eclampsia.[1] Both conditions usually occur during the later stages of pregnancy, or sometimes after childbirth. "HELLP" is an abbreviation of the three main features of the syndrome:[2]


Zika report: skin rash common
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乳房檢查 張醫師

乳癌
美國 1/2 婦產科開
歐洲 3/4 婦產科開
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說明之後 informed consent
標準作業流程
技法
推撥 screen
搓 confirm 揉
淋巴結， 縮下巴摸
形狀, 大小, 固定性, 移動性, 分泌物
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Ovoid shape
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Positive finding
Cannot distinguish cancer, benign
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Male
Paget disease
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BRCA1
15% TW AD
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醫學六大核心能力
記憶方式：MISPPP （I 3P SM）

  1. Medical knowledge （醫學知識）
  2. Interpersonal commmunication（人際及溝通技能）
  3. System-based practice（制度下之臨床工作）
  4. Patient care （病人照顧）
  5. Profesionalism （專業素養）
  6. Practice-based learning and improvement （工作中學習成長)
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