Oncology 腫六點

腫瘤科病房一定會被問的腫六點，可以快速的掌握一個癌症病人從最初的表現到診斷、期別、疾病，治療計畫、治療的效果及副作用、以及現在正在產生的問題，從這六點來整理一個癌症病人的發病經過。

Initial presentation
Definite diagnosis
Stage and disease extent
Treatment plan
Effect and side effect
Ongoing problem

敗血症/敗血性休克處理策略 Sepsis/Septic shock Management Strategy

Definition 定義
首先先來看看內科聖經Harrison裡對bacteremia, sepsis, septic shock的定義
Bacteremia 菌血症
Presence of bacteria in blood, as evidenced by positive blood cultures
Signs of possibly harmful systemic response
Two or more of the following conditions: (1) fever (oral temperature >38°C [>100.4°F]) or hypothermia (<36°C [<96.8°F]); (2) tachypnea (>24 breaths/min); (3) tachycardia (heart rate >90 beats/min); (4) leukocytosis (>12,000/μL), leukopenia (<4000/μL), or >10% bands
Sepsis (or severe sepsis) 敗血症
The harmful host response to infection; systemic response to proven or suspected infection plus some degree of organ hypofunction, i.e.:
1. Cardiovascular: SBP ≤90 mmHg or MAP ≤70 mmHg that responds to administration of IV fluid
2. Renal: U/O <0.5 mL/kg per hour for 1 h despite adequate fluid resuscitation
3. Respiratory: Pao2/FiO2 ≤250 or, if the lung is the only dysfunctional organ, ≤200
4. Hematologic: Platelet count <80,000/μL or 50% decrease in platelet count from highest value recorded over previous 3 days
5. Unexplained metabolic acidosis: A pH ≤7.30 or a base deficit ≥5.0 mEq/L and a plasma lactate level >1.5 times upper limit of normal for reporting lab
Septic shock 敗血性休克
Sepsis with hypotension (SBP <90 mmHg, or 40 mmHg less than patient’s normal blood pressure) for at least 1 h despite adequate fluid resuscitation or need for vasopressors to maintain SBP ≥90 mmHg or MAP ≥70 mmHg
Refractory septic shock 頑固性敗血性休克
Septic shock that lasts for >1 h and does not respond to fluid or pressor administration

敗血症(Sepsis)是人類宿主對抗病原菌(細菌、黴菌、病毒)產生的一連串全身性發炎反應，包含細胞介質的釋放 、驅使中性球細胞到達感染部位、微血管通透性的增加(使血流可到達感染部位)等等，然而人體過度的發炎反應可能反而造成更嚴重的後果。

敗血症(Severe sepsis已不再獨立出來一個名詞)及嚴重敗血性休克的處理，需要及早的處理。

Treatment 治療與處置

抗生素的使用


Reference: 1. Harrison's Principles of Internal Medicine, 19 edition

Fungal infection 黴菌感染相關議題

黴菌感染在臨床上是一個頗為棘手的問題，特別是發生在免疫不全的病人身上，需要特別的留意，除了在抗生素上的使用需注意抗菌譜外，也須根據臨床上的證據評估感染的可能性，給出合適的治療，避免走向嚴重併發症如敗血性休克及死亡。

黴菌分類 Fungus classification
Yeast - Candida spp., Cryptococcus spp., Trichosporon, Rhodotorula
Dimorphic - Blastomycosis, Paracoccidiomycosis, Coccidioidomycosis, Histoplasmosis, Sporotrichosis, Talaromyces
Mold - Aspergillus spp., Mucorymycosis, Fusariosis


抗黴菌圖譜 Anti-fungal agents spectrum

Reference:
1. Dodds Ashley, Elizabeth & Lewis, Russell & Lewis, James & Martin, Craig & Andes, David. (2006). Pharmacology of Systemic Antifungal Agents. Clinical Infectious Diseases - CLIN INFECT DIS. 43. 10.1086/504492.

黴菌感染臨床上判斷是否為疾病的三種可能性判斷，根據宿主因素、微生物學證據、病理切片、黴菌培養證據可分為Probable, Possible, Proven三種，再根據可能性投予抗黴菌用藥
Possible
1 host + 1 clinical but no mycobiological support
Probable
1 host + 1 microbiology + 1 clinical
Positive galactomannan or beta-D-glucan
Positive sputum or BAL culture
Prove
Histopathology + Culture

Chest X ray sign 常見胸部X光徵象

Kerley lines: cardiogenic pulmonary edema

A line: linear opacities extending from the periphery to the hila; they are caused by distention of anastomotic channels between peripheral and central lymphatics
B line:  short horizontal lines situated perpendicularly to the pleural surface at the lung base; they represent edema of the interlobular septa
C line: reticular opacities at the lung base, representing Kerley's B lines en face.

Reference:
1. Kerley's A, B, and C Lines, IMAGES IN CLINICAL MEDICINE, NEJM, 2009, https://www.nejm.org/doi/full/10.1056/NEJMicm0708489

休克分類 Shock classification

分布性休克 Distributive
Septic
Non-septic
Neurogenic shock
Anaphylactic shock

心因性休克 Cardiogenic
Myocardial infarction
Acute valvular damage
Arrhythmia

低血容性休克 Hypovolemic
Hemorrhagic
Non-hemorrhagic(Burns, GI losses)

阻塞性休克Obstructive
Massive pulmonary embolism
Tension pneumothorax
Cardiac tamponade

混合性休克 Mixed/unknown
Endocrine (eg, adrenal insufficiency, thyrotoxicosis, myxedema coma)
Metabolic (eg, acidosis, hypothermia)
Other – Polytrauma with more than one shock category, acute shock etiology with pre-existing cardiac disease, late under-resuscitated shock, miscellaneous poisonings

Ref:
1. Differential Diagnosis, third edition, Churchill's Pocketbooks
2. Shock(Circulatory) Ｗikipedia, https://en.wikipedia.org/wiki/Shock_(circulatory)

常見心電圖 ECG Criteria

RBBB
QRS duration > 120 ms
rsR’ “bunny ear” pattern in the anterior precordial leads (leads V1-V3)
Slurred S waves in leads I, aVL and frequently V5 and V6

Mariot Practical Electrocardiography
Lead V1 Late intrinsicoid (R' peak or lateR peak), M-shaped QRS (RSR'); sometimes wideR or qR
Lead V6 Early intrinsicoid (R peak), wide S wave
Lead I Wide S wave

LBBB
QRS duration > 120 ms
Absence of Q wave in leads I, V5 and V6
Monomorphic R wave in I, V5 and V6
ST and T wave displacement opposite to the major deflection of the QRS complex

Ref:
1. Helio, Learn the Heart, https://www.healio.com/cardiology/learn-the-heart/ecg-review/ecg-topic-reviews-and-criteria/right-bundle-branch-block-review
2. https://www.healio.com/cardiology/learn-the-heart/ecg-review/ecg-topic-reviews-and-criteria/left-bundle-branch-block-lbbb-review

3. Marriott's Practical Electrocardiography, 12e 

急性冠心症候群 Acute Coronary Syndrome 心電圖診斷

心電圖診斷 ECG Diagnosis

STEMI ST段上升心肌梗塞

1. 以J point為基準，產生新的連續兩個lead ST波段 ≥0.1 mV(1小格), 例外在V2, V3這兩個lead, 40歲以上男性 ≥0.2 mV(2小格)，40歲以下男性 ≥0.25 mV(2.5小格), 女性不限年齡≥0.15 mV(1.5小格)。

2. 新的LBBB

NSTEMI 非ST段上升心肌梗塞

產生新的連續兩個水平的(horizontal)或下斜的(Down-sloping)lead ST depression ≥ 0.05mV(半小格)，並且或者連續兩個lead T波下降超過1mm(1小格)，合併有一個prominent R wave或R/S ration>1。

梗塞位置 Location

V1-V2 – Anteroseptal
V3-V4 – Anteroapical
V5-V6 – Anterolateral
I, aVL – Lateral
II, III, aVF – Inferior

右冠狀動脈阻塞 RCA occlusion
1. ST depression in lead I
2. ST elevation lead III>II
   Proximal: ST elevation 1mm with positive T wave
   Distal: ST isoelectric with positive T wave in V4R

左冠狀動脈迴旋枝阻塞 LCX occlusion
1. ST elevation in lead II>III
2. ST isoelectric or elevated in lead I
3. ST isoelectric or depressed with negative T wave in T4R

Extension to posterior wall
=> ST depression in precordial lead
Extension to lateral wall
=> ST elevation in lead I, aVL, V5, V6

Ref:

1. Fourth Universal Definition of Myocardial Infarction, 2018 ESC/ACCF/AHA/WHF Expert Consensus Document
2. ECG in emergency Decision Making 2006 2nd Edition

# STEMI and potiential Equivalents 看到這些也要當成可能是STEMI發生

Ref: Electrocardiographic Diagnosis of Life-Threatening STEMI Equivalents: When Every Minute Counts∗ https://www.jacc.org/doi/10.1016/j.jaccas.2019.10.030

理學檢查-心音 Physical Examination-Heart sound

S1：高頻音，注意強度及是否有分裂(Splitting)，在左胸骨側可能會聽到正常的分裂S1心音，S1的大小與心室收縮力有關，在1st degree AV block時也會下降。在RBBB時可在Tricuspid area聽到分裂的S1。

S2：高頻音
Split S2
Physiologic：正常情況下主動脈瓣(A1)比肺動脈(P2)提前關閉，S2在吸氣時因Venous return增加，Pulmonary valve會更晚關閉，S2分裂心音會更明顯，可在Pulmonary area聽到。
Narrow or Single S2：如果吸氣時聽不到Split S2，如肺高壓時(Pulmonary Hypertension)因肺阻力大肺動脈瓣早期收縮 (Early pulmonic valve closure)，或Mild to moderate Aortic Stenosis (Delayed aortic valve closure)。或有一瓣膜消失或大片心室中膈缺損 (VSD)。
Wide S2 split：RBBB
Wide & Fixed S2 split：ASD/RV failure
Paradoxical (Reverse) S2 split：Severe Aortic Stenosis

S3：低頻音，為心房早期收縮射血入心室時產生turbulance之聲音。小於40歲且為運動員或體重瘦的人可能會聽到生理性的S3，大於40歲若聽到則有hemodynamic相關問題，如心室衰竭ventricular failure、左心室擴大等等。

S4：低頻音，為心房晚期收縮射血時，心室舒張異常(LV compliance)造成之聲音，如

心雜音Murmurs： 與S1, S2心音不同，時間上較長。
Loudness (Levine grade)
Gr 1: initially unaware
Gr 2: initially aware
Gr 3: Markable; no thrills
Gr 4: Complte; thrills
Gr 5: edge; thrills
Gr 6: no touch; thrills

Thrill震顫: 觸覺可以感覺得到胸壁震動


Systolic murmurs：S1與S2之間，常見為瓣膜性心臟病或正常生理現象
AS: Midsystolic, at Right base, Erb's point, Apex
HCMP: LLSB, Erb's point
PS/ASD: Left base
MR: Holosystolic, Apex
TR: Holosystolic, LLSB
VSD: Holosystolic, LLSB
Diastolic murmurs：S2與S1之間，常見為瓣膜性心臟病
AR: Early diastolic, at Right base, Erb's point, Apex
MS: Apex

Notes筆記：高頻音用聽診器diaphragm面聽，低頻音用bell面聽，輕放即可。


Ref:
1. Bates' Guide to Physical Examination and History-Taking, 11th edition
2. NTUH teaching

慢性心臟衰竭處理 Chronic Heart Failure Management

ESC guideline 2016

Ref: 1. ESC guidelines, 2016, https://academic.oup.com/eurheartj/article/37/27/2129/1748921

Evidence of Survival benefit:
ACEI: Enalapril(Sintec, Synbot), Captopril(CEporin), Ramipril(Tritace), Trandolapril
ARB: Losartan(Cozaar), Valsartan(Diovan), Candesartan(Blopress), Telmisartan(Micardis) (ARB usage When ACEI is not tolerated)
Beta-blockers: Carvedilol(Dilatrend), Metoprolol(Betaloc), Bisoprolol(Concor)
MRA: Spironolactone(Aldactone), Eplerenone(Inspra)
If inhibitor: Ivabradine, Sinus rhythm, HR>=70bpm, LVEF<=35%
ARNI: Sacubitril/Valsartan(Entresto)

肺功能檢查判讀 Pulmonary Function Test Interpretation

Normal range:   TLC＞80%, FVC＞80%,   FEV1＞75%, FEV1 /FVC (%)＞75%,  Flow rate＞60% 

ILD(Interstitial Lung Disease): 侷限性肺病, VC↓(For  ILD,  DLCO↓ ) 

Memo: FEV1% 隨著年齡增加而些微下降, FEV1與prognosis & severity有關

Ref: Uptodate,   2019 

類固醇劑量及轉換 Steroids dose calculation

Notes;
1.類固醇劑量可由淺加上去，如10mg q12h iv，如果用到20mg q12h，須慢慢taper減量下來，不可直接delete，可5-7天taper減量一次，每3天評估一次類固醇反應。使用超過3週，需taper劑量。
2.0.5mg/kg anti-inflammation effect即足夠，1mg/kg有immunosuppression effect‧(ref: VS謝松洲)，超過20mg/day會有immunosuppress效果，小於7.5mg/day則不會有免疫抑制效果。
3.High dose steroid 可能會抑制 prostacyclin，導致acute renal failure。
4.Steroid造成的hyperglycemia有極限，genomic effect有天花板效應。
5.Steroid divided dose efficacy > once daily dose。
6.NSAID binding protein會造成hypertension用藥減低效果。
7.NSAID GI risk: 幾個小時即開始影響; CV risk則較久，2~3週後開始影響。
8.Steven Johnson Syndrome類固醇可以從10mg q12h上調，每天觀察有沒有新的lesion，如果沒有，維持劑量即可，不可一下子打太強，之後一停再復發會更嚴重。

Reference:
1. 台大處方集, 2019 2. Textbook