[醫如往常] Senior Clerkship Day 8: 放射腫瘤學

放射腫瘤學的高科技進展Radiotherapy

許醫師

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3D conformal RT, 順形:順腫瘤形

DVH; Dose-volume histogram

攝護腺癌要注意: 放射性膀胱炎 放射性直腸炎

頭頸部要注意:唾液腺喪失-> 口乾

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IMRT; Intensity modulated RT

Multi leaf collimator MLC

Reverse therapy plan

5-7 Angle

減少副作用

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IGRT image-guided RT

EPID; Electronic Portal Imaging Devices

Motion view IGRT with active breathing control(ABC)

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Kv 光電效應

Mv 康普頓效應, 軟組織不清楚

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Elekta synergy

Kv based CT corn beam 在MVRT的90度方向

可以六維度矯正(xyz+deviation)

因為是椎型，only cental image is good

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Fiducial marker

金(gold)

Marker may migration, wait 1 weeks before RT

Artifact

Now, RFID

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最新用MRI導引

減少干擾，放射線

軟組織清楚

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X-ray 直線加速撞擊，常態分佈spectrum

Gamma ray fixed: Co60 2 kinds of photon

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Tomotherapy 螺旋刀

Time consuming

VMAT VOLUMETRIC 瑞速刀

Circle

主要用在攝護腺，頭頸，total scalp

Lung很敏感，非常不適合

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Gamma knife

Radiosurgery

Dr. Lars Leksell, Sweden

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Proton

Bragg peak

Neutron contamination

迴旋加速Cyclotron，同步加速Synchrotron

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Heavy carbon

Fragmented tail

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[醫如往常] Senior Clerkship Day 8: Ob/Gyn Hysteroscopy, SILS, 病歷寫作

Hysteroscopy 楊教授

Resectoscope

TCR, Trans Cervical Resection

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Timing: proliferative follicular phase

Contraindication: PID, Pregnancy, cervical cancer

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Pre-TCR

Ultrasonography

Laminaria 海草棒 吸水撐大cervix

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Common

Endometrial polyp, sono hyperechoic

Intrauterine myoma type 0

Submucous myoma type I

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Septate可以用

Bicornuate 不能用

用3D sono看fundus

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Asherman syndrome

Uterine adhesion

Central 比較好

Marginal type 不適合

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Post operation

No need for NPO

Oral antibiotics

Discharge 當天或隔天

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Afternoon Meeting

Single-port laparoscopy(SPL) single-incision laparoscopic surgery (SILS)

• Blood loss
• Diet initiation
• Hospitalization

NTUH用手套改造

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IVF醫學史

成大婦產部 許教授: 2010諾貝爾獎IVF之父 RG Edwards惟一台灣學生

384-322 BC Aristotle:  "Seeds" theory

1578-1657 William Harvey:  "Sperm" theory

Leeuwenhoek: First Sperm study

Dalenpatus: homunculus

1826 Von Bear :Modern father of embryology: Oocytes

1939 Pincus rabbit

1959 張明覺 試管嬰兒之父 rabbit

Polge 冷凍精液大師, 台大鄭登貴指導教授

1967 Patrick Steptoe 腹腔鏡大師

102次失敗

1978 第一成功IVF: Louise Brown華誕

1980 Bourn Hall Clinic

1987 台大首例IVF
 

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鍾醫師 病歷寫作

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General Gynecology

• Introduction:

– This __ year old, GxPx woman is a patient with a

history of A, B, C under __, and D.

• Why is she here?

– She began to have _____ since….

– She experienced _____ for…..

• Course of disease or treatment:

– She went to an LMD and…..

• Echo? CT? Lab?

• Diagnosis?

• Medications given? Surgeries done?• At our hospital:

– Came to our OPD for second opinion?

– Transferred to our ER?

• Echo? CT? Lab?

• Medications given? Surgeries done?

• Impression?

• Plan:

– Therefore, under the impression of _______, she

was admitted for_______.

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General Obstetrics

• Introduction:

– This __ year old, GxPx woman is pregnant for GA __.

– She has a history of A, B, C under __, and D.

• Prenatal care:

– She received prenatal care at ____

– Abnormal or normal results?

• Why is she here?

– APH? Preterm uterine contraction? Previous C/S? Placenta

previa? .....

• Plan:

– Due to labor sign/PROM/Preterm labor/Previous C/S….,

she was admitted for delivery/scheduled C/S, etc.

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GYN oncology

• Introduction:

– This __ year old, GxPx woman is a patient with a history of

A, B, C under __, and D.

• Why is she here?

– Vaginal bleeding? Post-menopausal bleeding? PAP smear

results? Abdominal pain? Accidental findings?

• Course of disease or treatment:

– She went to ____ and did this there.

• Echo? CT? Lab?

• Diagnosis?

• Medications given? Surgeries done?

• Pathology?• At our hospital:

– Came to our OPD for second opinion?

– Transferred to our ER?

• Echo? CT? Lab?

• Medications given? Surgeries done?

• Impression?

• Plan:

– Therefore, under the impression of _______, she

was admitted for_______.

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OBGYN history:

– GxPx, NSD? C/S?

– Menstruation cycle, I/D

– LMP, PMP?

– Past history

– Operations

– PAP smear• Pelvic examination:

– Vagina/vulva: grossly normal

– Cervix(VP): grossly normal, lifting pain?

– Discharge: mild whitish mucoid? Bloody?

– Uterus: Enlarged? About GA ___

– Adnexa: tenderness? Rebounding pain? Mass

noted? (egg size, tennis ball size, etc….)

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Endometrial cancer

Vaginal bleeding stage 1A

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Pubic symphysis week 12

Umbilicus week 20

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Echo trans-Abdominal/Vaginal:

Uterus

Avfl or Rvfl

(A+B)*C*D

EM

LOV

ROV sand like chocolate cyst

CDS: ascites or free

[醫如往常] Senior Clerkship Day 7: Ob/Gyn IUI; Intrauterine insemination

李醫師

台灣

IVF; in vitro fertilization 一次12-15萬

IUI, Intrauterine insemination 一次八千元

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只要一顆dominant oocyte

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LH 試紙很貴，市面一張兩百元，可以在網路找便宜的

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月經往前十四天

Day 12, 14, 16

行房兩天一次

平均存活三天

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First line

Estrogen inhibitor: clomiphene

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NTUH IUI採用Swim up方式

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小於38歲 三次IUI失敗就換進階療法

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[醫如往常] Senior Clerkship Day 5: Ob/Gyn PCOS; polycystic ovary syndrome

PCOS; polycystic ovary syndrome
陳教授

Common symptoms & signs

• Obesity (40-60%)
• Acanthosis nigricans 黑黑的

• Mediterranean alopecia
• Acnes (10-25%)

• Infertility (50-80%)
• Hirsutism (30-60%)

• 東方人obesity, hertutism不明顯

Mother to infant effect

• Imperforated hymen
• Ambiguous genitalis

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Diagnosis

Hyperandrogenism

Oligomenorrhea/oligo ovulation: Less than 9 menstrual cycles per year

Polycystic > 12 antral follicles, 一邊就可以

• 1990 NIH 前兩個
• 2003 Rotterdam 三取二, 最常用
• 2009AE- PCOS 第一加上後兩取一

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Ddx

• sertoli leydig cell tumor
• Congenital adrenal hyperplasia, hoarseness
• Cushing syndrome, 最早就要鑒別
• Thyroid
• Hypogonadism, hypo hypo

• Hyperprolactinemia

• Idiopathic hirsutism, familial, 有月經
• WNT4 syndrome, no uterus
• Androgen receptor insensitivity
• Medication

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Biomaker

Free testosterone

Free androgen index (FAI)

FAI(%)=total testosterone / SHBG X 100

LH/FSH>3 現在不用了

Unopposed estrogen

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Prevalence 5-10%

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Pathophysiology

Insulin resistance

Liver SHBG↓

Low grade inflammation

Androgen stimulate early follicle

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Granulosal cell↑

Inhibin B ↑

Anti Mullerian hormone↑ 抑制ovulation

DHEAS dominant

More Acnes

Less obesity

Suppress myostatin

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PTEN, 抑制FSH, 影響AKT活化

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Tx

• ovarian drilling 不會改善代謝
• Life style modification, 減重5%
• Insulin sensitizer, metfomin懷孕可以用 至少半年, ppar gamma agonist
• Low glycemic index food
• ART for 不適合懷孕的人
• Gonadotropin 小心OHSS
• Clomiphene citrate對於想懷孕的人比較好， 75%成功， 六次無效換藥
• Aromatase inhibitor Letrozole更好，不過是off label use, 因為可能增加胎兒CHD

Oral contraceptive pills只能治療normal weight PCOS

胖的增加metabolic syndrome, insulin resistance

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Complications

• Type II DM
• CAD, stroke
• Hypertension
• NAFLD, NASH

The prevalence of metabolic syndrome in young Taiwanese women with PCOS is around 17 %. (reference population is 6% in Taipei). ~ MJ Chen et al, Hum Reprod. 2006 September; 21(9):2266-71

用array CGH 找出高風險病人

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測DHEA, androstenedine做研究

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CRP 預測CVD風險

Endothelium function測carotid flow

Follistatin影響排卵，anti-inflammation

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新發展薏仁

Adlay extract suppress androgen, thecal cell

[醫如往常] Senior Clerkship Day 3: 放射腫瘤學 Overview

放射腫瘤學

成教授

傳統的造影需要搬鉛塊到機器上

因此有只錄取男生不成文規定

以前3D, 現在最流行IMRT

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單位

• Gy 研究用
• cGy 臨床=Rad

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俗語

電療來自台語電光，國外要講放療

• 大電：體外 teletherapy
• 小電：體內 Brachytherapy

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• 電磁波
• Co60 落後地區使用(gamma ray)射源固定 1.25 MeV 1千萬元
• Linear Accelerator 非射源(X-ray) 6-18 MeV 5-15千萬元
• 粒子 200-250 MeV 有撞擊生物效應
• Proton 15-30億元
• Carbon 50-70億元

目前只有小孩有Evidence用Proton比較好

其他粒子都是有錢人的東西

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RBE (Relative Biological Effectiveness)(撞擊生物效應)

• IMRT 1
• Proton 1.1
• Carbon 1.2

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Fractionation

• Hyper
• Hypo
• Accelerated
• mixed

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Metastasis dosage

• Bone 3000/300cGy/10 fr
• Pain relief 2400/400cGy/6 fr
• Brain 3000/300cGy/10 fr or 3500/250cGy/14 fr

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粒子治療

最早是由日本國立放射研究院發展

• 日立
• 三菱
• 住友

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[醫如往常] Senior Clerkship Day 5: Ob/Gyn Grand Round: OAB; overactive bladder syndrome

OAB; overactive bladder syndrome

R1 Dr. 謝 / Prof. 林

Symptom diagnosis: Urinary Urgent ± urgency incontinence, frequency or nocturia

• Urgency : sudden compelling desire to urinate, difficult to defer
• Frequency : > 8 times / 24hrs
• Nocturia : > 1 times, wake to void
• OAB-dry, OAB-wet : incontinence or not
• Dry37%
• Wet63%

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Impacts on quality of life

Depression

Daily activity

UTI

Falls, fracture

Quality of sleep

Skin infection or irritation

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Pathophysiology

• Idiopathic
• Inflammation
• Myogenic  ( structure, receptors of cell membrane )
• Enhanced coupling tetanic contraction
• Increased connective tissue
• M2: inhibit smooth muscle relaxation
• M3: contract smooth muscle
• Beta 3: smooth muscle relaxation
• Neuroplasticity ( NGF, urothelium hypersensitivity, new spinal circuit,
  alter Na channel function, reawaken silent C-fiber )
• 5-HT (serotonin) deficit ( Brain stem, spinal cord )
• Low pH, high K
• Afferent plasticity

TCA (5HT) can inhibit circuit

Lidocaine inhibit sodium

NGF antibody

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Etiology

Idiopathic

Neurologic

Spinal cord injury, Stroke, Multiple sclerosis, Dementia, Parkinson disease

Diabetic neuropathy

Inflammatory

UTI, post-RT

Structural

Tumor, BPH, Stones, post-OP

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Diagnosis

1. Review medical history, and present symptoms
2. Bladder diary: Record everyday urinary situation
3. Exclude other disease, such as stress incontinence, mixed urinary incontinence, overflow incontinence, and transient incontinence
4. Postvoid residual test, Urodynamic study ( not first-line evaluation )

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OABSS; overactive bladder symptom score questionnaire

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Pdet=Pves-Pabd

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1. Behavioral therapies
1. lifestyle modification, bladder training, pelvic floor muscle therapy,
2. Pharmacotherapy
1. antimuscarinics, Beta-3 agonists, Botulinum toxins, TCA, Capsaicin
3. Surgery
1. Augmentation cystoplasty, Sacral Neuromodulation, percutaneous tibial nerve stimulation
4. Treat specific causes
1. UTI
2. Atrophic urethritis

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Frequent nocturia episodes, a suboptimal response to treatment, and small bladder capacity predict the need for persistent antimuscarinic therapy or re-treatment after discontinuation of antimuscarinics in female overactive bladder

Menopause, 2016 ( in press )

For predicting persistent or re-treatment for female OAB

• Suboptimal response
• Nocturia<2
• VSD: volume at strong desire to void

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Discussion

1. Nocturia : a new predictor of the need of persistent treatment or re-treatment
2. If the change of OABSS is less than 3, continuous therapy is recommended
3. Strong desire volume is an another predictor, thus, women with small bladder
   capacity may need continuous therapy
4. Urodynamic study, Age, OABSS, urinary NGF/Cr, etc. are not predictors in this study.
5. Limitation : sample size, only one medication (solifenacin), low ROC area 

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林教授講評

Severe IC(interstitial cystitis), OAB(Overactive bladder) overlap

很難治，轉給泌尿科

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Urodynamics

• Anatomy: POP; Pelvic organ prolapse
• Functional: OAB, SUI; Stress Urinary Incontinence
• LUTD; Lower Urinary Tract Dysfunction
• Sexual dysfunction: FSFI: Female Sexual Function Index
• Anorectal incontinence

[醫如往常] Senior Clerkship Day 3: Ob/Gyn Grand Round: Nerve-sparring radical hysterectomy

NSRH/CRH for cervical cancer

Nerve-sparring radical hysterectomy

Conventional radical hysterectomy

Outcome 沒有顯著差異

Quality of life 有顯著差異

Surgery Indication: 1B to 2A

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Cardinal lig. dissection is the key element

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Sympathetic T10-L2 Para-aortic nerve → Sup. Hypogastric plexus

Parasympathetic L2-4 Pelvic splanchnic nerve→Inf. Hypogastric plexus (IHP)

(uterosarcral lig.)

Bladder br. of IHP save part of vesicouterine lig.

Hypogastric nerve lat. Border of mesoderm

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F. Mota: EORTC Classification of radical hysterectomy

Classification of radical hysterectomy adopted by the Gynecological Cancer Group of the European Organization for Research and Treatment of Cancer

1. Simple hysterectomy (type I).

2. Modified radical hysterectomy (type II): Theuterus, paracervical tissues, and upper vagina (1–2 cm) are removed after dissection of the uretersto the point of their entry to the bladder. The uterine arteries are ligated, and the medial half of the parametria (there was no consensus in this concept) and proximal uterosacral ligaments are resected.

3. Radical hysterectomy (type III): En bloc removal of the uterus with the upper third of the vagina along with the paravaginal and paracervical tissues. The uterine vessels are ligated at their origin, and the entire width of the parametria is resected bilaterally. Removal of as much of the uterosacral ligaments as possible.

4. Extended radical hysterectomy (type IV): Differ from the type III procedure—three fourths of the vagina and paravaginal tissue are excised.

5. Partial exenteration (type V): The terminal ureteror a segment of the bladder or rectum is removed along with the uterus and parametria (supralevatorial).

A) Types II–V hysterectomies are completed witha systematic bilateral pelvic lymphadenectomy,half the way along the common iliac artery downto the femoral ring, including the presacral, bothexternal, internal, and interiliac and the obturatornodes (at least to the level of the obturator nerve).

B) Removal of the tubes and ovaries is not part ofradical hysterectomy per se.

F. MOTA, Int J Gynecol Cancer 2008, 18, 1136–1138

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FIGO stage

Endometrial cancer, Figo stage II

Primary tumor (T)
TNM	FIGO	Surgical-Pathologic Findings
Categories	Stages
TX		Primary tumor cannot be assessed
T0		No evidence of primary tumor
Tis		Carcinoma in situ (preinvasive carcinoma)
T1	I	Cervical carcinoma confined to the cervix (disregard extension to the corpus)
T1a	IA	Invasive carcinoma diagnosed only by microscopy; stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less; vascular space involvement, venous or lymphatic, does not affect classification
T1a1	IA1	Measured stromal invasion ≤ 3.0 mm in depth and ≤ 7.0 mm in horizontal spread
T1a2	IA2	Measured stromal invasion > 3.0 mm and ≤ 5.0 mm with a horizontal spread ≤ 7.0 mm
T1b	IB	Clinically visible lesion confined to the cervix or microscopic lesion greater than T1a/IA2
T1b1	IB1	Clinically visible lesion ≤ 4.0 cm in greatest dimension
T1b2	IB2	Clinically visible lesion > 4.0 cm in greatest dimension
T2	II	Cervical carcinoma invades beyond uterus but not to pelvic wall or to lower third of vagina
T2a	IIA	Tumor without parametrial invasion
T2a1	IIA1	Clinically visible lesion ≤ 4.0 cm in greatest dimension
T2a2	IIA2	Clinically visible lesion > 4.0 cm in greatest dimension
T2b	IIB	Tumor with parametrial invasion
T3	III	Tumor extends to pelvic wall and/or involves lower third of vagina and/or causes hydronephrosis or nonfunctional kidney
T3a	IIIA	Tumor involves lower third of vagina, no extension to pelvic wall
T3b	IIIB	Tumor extends to pelvic wall and/or causes hydronephrosis or nonfunctional kidney
T4	IV	Tumor invades mucosa of bladder or rectum and/or extends beyond true pelvis (bullous edema is not sufficient to classify a tumor as T4)
T4a	IVA	Tumor invades mucosa of bladder or rectum (bullous edema is not sufficient to classify a tumor as T4)
T4b	IVB	Tumor extends beyond true pelvis
Regional lymph nodes (N)
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Regional lymph node metastasis
Distant metastasis (M)
M0	No distant metastasis
M1	Distant metastasis (including peritoneal spread; involvement of supraclavicular, mediastinal, or para-aortic lymph nodes; and lung, liver, or bone)

http://emedicine.medscape.com/article/2006486-overview

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台灣40% 都要 RT

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Hydronephros when pregnancy is mostly at the right side due to right Ureter angulation

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