Quyen Nguyen: Color-coded surgery

譯者: 俊偉 盧 審譯者: Joyce Chou

I want to talk to you

我想跟各位談談

about one of the biggest myths in medicine,

醫學界最大的迷思之一

and that is the idea

這個迷思就是

that all we need are more medical breakthroughs

只要我們在醫學界有更多的突破

and then all of our problems will be solved.

一切問題就能迎刃而解

Our society loves to romanticize

世人喜歡把這種事想得浪漫

the idea of the single, solo inventor

某位發明家隻身奮鬥

who, working late in the lab one night,

某晚在實驗室工作到很晚

makes an earthshaking discovery,

有了驚為天人的發現

and voila, overnight everything's changed.

突然，一夕之間全都變得不一樣了

That's a very appealing picture,

這樣的畫面非常吸引人

however, it's just not true.

然而，實情並非如此

In fact, medicine today is a team sport.

實際上，現今的醫學是種團隊運動

And in many ways,

很多方面來說

it always has been.

一直都是如此

I'd like to share with you a story

我想和大家分享一則故事

about how I've experienced this very dramatically

這故事是我在工作上

in my own work.

親身經歷的戲劇化改變

I'm a surgeon,

我是名外科醫生

and we surgeons have always had

身為外科醫生

this special relationship with light.

我們和光線有種奇妙的關係

When I make an incision inside a patient's body, it's dark.

當我動刀切入病患的身體時，裡頭是暗的

We need to shine light to see what we're doing.

我們要打光才能知道我們正在進行什麼動作

And this is why, traditionally,

這就是為什麼傳統上

surgeries have always started so early in the morning --

手術都在一大早的時候進行

to take advantage of daylight hours.

以便利用白天的光線

And if you look at historical pictures

假如你看看歷史照片

of the early operating rooms,

早期的手術室

they have been on top of buildings.

都位在建築物的頂樓

For example, this is the oldest operating room in the Western world,

例如：這張是西方世界最早的手術室

in London,

位在倫敦

where the operating room

這間手術室

is actually on top of a church

位在教堂的頂樓

with a skylight coming in.

上頭有日光照進來

And then this is a picture

再來這張照片是

of one of the most famous hospitals in America.

美國最有名的醫院之一

This is Mass General in Boston.

這是波士頓的麻省總醫院

And do you know where the operating room is?

你知道手術室在哪嗎？

Here it is

在這裡

on the top of the building

醫院的頂樓

with plenty of windows to let light in.

上面開了很多窗戶引進光線

So nowadays in the operating room,

現今的手術室

we no longer need to use sunlight.

不再需要利用陽光

And because we no longer need to use sunlight,

因為我們不需要利用陽光

we have very specialized lights

我們有特製的燈光

that are made for the operating room.

專為手術室打造的燈

We have an opportunity

我們有機會

to bring in other kinds of lights --

引進其他種類的光線

lights that can allow us to see

這種光線可以讓我們看見

what we currently don't see.

目前我們看不到的地方

And this is what I think

這種光線就是

is the magic of fluorescence.

神奇的螢光

So let me back up a little bit.

我先把話題拉回以前

When we are in medical school,

當我們在醫學院的時候

we learn our anatomy from illustrations such as this

我們透過插圖學習解剖學，就像這張

where everything's color-coded.

各部位都用色彩區分

Nerves are yellow, arteries are red,

神經是黃的，動脈是紅的

veins are blue.

靜脈是藍的

That's so easy anybody could become a surgeon, right?

很簡單，每個人都可以當外科醫生，對吧？

However, when we have a real patient on the table,

然而，當我們在看手術台上的實體病人時

this is the same neck dissection --

這是相同的頸部解剖面

not so easy to tell the difference

不太易區分

between different structures.

不同組織的差異

We heard over the last couple days

過去幾天我們聽說

what an urgent problem

癌症至今仍是

cancer still is in our society,

我們所面臨的迫切問題

what a pressing need it is

我們有急迫的需求

for us to not have

不希望隨時會有人

one person die every minute.

因為癌症而死

Well if cancer can be caught early,

假如能夠早期發現癌症

enough such that someone can have their cancer taken out,

在最初時就透過手術

excised with surgery,

把腫瘤移除

I don't care if it has this gene or that gene,

我不管是有這個基因或那個基因

or if it has this protein or that protein,

或者有這種蛋白質或那種蛋白質

it's in the jar.

反正都丟到罐子了

It's done, it's out, you're cured of cancer.

手術完成，切除了，癌症治好了

This is how we excise cancers.

這是我們移除腫瘤手術的照片

We do our best, based upon our training

我們盡最大能力，依據過去的訓練

and the way the cancer looks and the way it feels

還有腫瘤的樣貌和感覺

and its relationship to other structures and all of our experience,

以及腫瘤與其他組織的關聯，還有過去的經驗

we say, you know what, the cancer's gone.

我們說，你知道嗎，腫瘤清除了

We've made a good job. We've taken it out.

很好，我們把腫瘤移除了

That's what the surgeon is saying in the operating room

外科醫生在手術室都會這樣說

when the patient's on the table.

當患者還在手術台上時

But then we actually don't know that it's all out.

可是我們其實不確定腫瘤是否都移除了

We actually have to take samples from the surgical bed,

我們必須從腫瘤床採取樣本

what's left behind in the patient,

以了解患者體內是否殘存腫瘤

and then send those bits to the pathology lab.

然後把樣本送到病理實驗室

In the meanwhile, the patient's on the operating room table.

這時，患者仍然躺在手術台上

The nurses, anesthesiologist, the surgeon,

護士、麻醉師、外科醫生

all the assistants are waiting around.

所有的助理都在等候

And we wait.

我們就這樣等著

The pathologist takes that sample,

病理師把樣本拿去

freezes it, cuts it, looks in the microscope one by one

冷凍、切開，一片片放在顯微鏡下觀察

and then calls back into the room.

然後回覆手術室

And that may be 20 minutes later per piece.

每件樣本大概要花20分鐘

So if you've sent three specimens,

所以假如你送三件樣本

it's an hour later.

要等上一小時

And very often they say,

通常他們會說

"You know what, points A and B are okay,

「你知道嗎，A點和B點都沒問題，

but point C, you still have some residual cancer there.

但是C點仍然殘留些許的腫瘤，

Please go cut that piece out."

請把殘留的腫瘤切除。」

So we go back and we do that again, and again.

所以我們就回去一次又一次再做手術

And this whole process:

這就是整個過程

"Okay you're done.

「好了，完成了，

We think the entire tumor is out."

我們認為腫瘤已經切除了。」

But very often several days later,

但通常幾天以後

the patient's gone home,

病患回家了

we get a phone call:

我們接到電話說：

"I'm sorry,

「抱歉，

once we looked at the final pathology,

我們看了最後的病理報告

once we looked at the final specimen,

我們看了最後的樣本

we actually found that there's a couple other spots

我們發現有些其他的點

where the margins are positive.

邊緣呈現陽性反應

There's still cancer in your patient."

患者的體內仍有腫瘤。」

So now you're faced with telling your patient, first of all,

所以首先要面對的是告訴患者

that they may need another surgery,

可能要再進行一次手術

or that they need additional therapy

或者額外的治療

such as radiation or chemotherapy.

像是放射線治療或化療

So wouldn't it be better

如果我們能夠知道

if we could really tell,

如果可以在手術時就知道

if the surgeon could really tell,

腫瘤是否仍然存在

whether or not there's still cancer on the surgical field?

這樣是不是更好？

I mean, in many ways, the way that we're doing it,

我的意思是，現階段我們進行手術時

we're still operating in the dark.

很多時候等於在黑暗中動刀

So in 2004, during my surgical residency,

2004年，當我在住院醫師期間

I had the great fortune

我很榮幸

to meet Dr. Roger Tsien,

遇見 Roger Chen 醫師

who went on to win the Nobel Prize for chemistry

後來他在2008年時

in 2008.

獲得諾貝爾化學獎

Roger and his team

Roger和他的團隊

were working on a way to detect cancer,

當時正在研究偵測腫瘤的方法

and they had a very clever molecule

他們後來研發出

that they had come up with.

一種非常神奇的分子

The molecule they had developed

他們研發出的分子

had three parts.

由三個部分構成

The main part of it is the blue part, polycation,

第一部分是藍色的聚陽離子

and it's basically very sticky

這東西很容易附著在

to every tissue in your body.

身體組織上

So imagine that you make a solution

想像一下你製做了一種溶液

full of this sticky material

裡頭都是這種高依附性物質

and inject it into the veins of someone who has cancer,

然後注射到癌症患者的靜脈

everything's going to get lit up.

接著全身各部位開始發亮

Nothing will be specific.

沒有什麼地方不會發亮

There's no specificity there.

看不出任何不同的地方

So they added two additional components.

所以他們添加了兩種成分

The first one is a polyanionic segment,

第一種是聚陰離子

which basically acts as a non-stick backing

具有反依附作用

like the back of a sticker.

就像貼紙下面那張不黏的底紙

So when those two are together, the molecule is neutral

當這兩種物質結合在一起時，分子變成中性

and nothing gets stuck down.

不會附著在組織上

And the two pieces are then linked

當這兩種物質結合在一起時

by something that can only be cut

必須使用特定的分子剪刀

if you have the right molecular scissors --

才能將兩者分開

for example, the kind of protease enzymes

像是腫瘤產生的

that tumors make.

蛋白酵素

So here in this situation,

在這種溶液裡

if you make a solution full of this three-part molecule

假如溶液裡含有這三種成分

along with the dye, which is shown in green,

同時含有綠色染劑

and you inject it into the vein

把這溶液注射到

of someone who has cancer,

癌症患者的靜脈裡

normal tissue can't cut it.

正常組織無法切斷分子鍵

The molecule passes through and gets excreted.

溶液的分子流經組織，然後代謝掉

However, in the presence of the tumor,

然而，當有腫瘤的時後

now there are molecular scissors

裡面就有分子剪刀

that can break this molecule apart

可以把分子分開

right there at the cleavable site.

從可以切開的地方切斷

And now, boom,

接著，蹦

the tumor labels itself

腫瘤發亮了

and it gets fluorescent.

並且發出螢光

So here's an example of a nerve

這邊以神經為例

that has tumor surrounding it.

神經的周遭有腫瘤

Can you tell where the tumor is?

你看得出來腫瘤在哪嗎？

I couldn't when I was working on this.

我在那時候根本看不出來

But here it is. It's fluorescent.

不過現在有了，螢光的地方就是了

Now it's green.

看起來是綠色的

See, so every single one in the audience

在座的每位聽眾

now can tell where the cancer is.

都看得出來腫瘤在哪

We can tell in the operating room, in the field,

我們在手術室能夠以分子般的細微程度

at a molecular level,

判斷腫瘤位置

where is the cancer and what the surgeon needs to do

知道哪邊需要進行手術

and how much more work they need to do

以及需要做到什麼程度

to cut that out.

才能將腫瘤切除

And the cool thing about fluorescence

螢光最炫的地方在於

is that it's not only bright,

螢光不只會發亮

it actually can shine through tissue.

還能穿透組織發亮

The light that the fluorescence emits

螢光所發出光線

can go through tissue.

能夠穿透組織

So even if the tumor is not right on the surface,

就算腫瘤不在組織的表面

you'll still be able to see it.

一樣可以看得到

In this movie, you can see

這段影片可以看見

that the tumor is green.

腫瘤呈現綠色

There's actually normal muscle on top of it. See that?

正常肌肉組織在上面，看到沒？

And I'm peeling that muscle away.

我把肌肉剝開

But even before I peel that muscle away,

不過就算還沒把肌肉剝開

you saw that there was a tumor underneath.

仍然看得到底下有腫瘤

So that's the beauty of having a tumor

散發出螢光的腫瘤

that's labeled with fluorescent molecules.

看起來就是這麼漂亮

That you can, not only see the margins

你不只能夠以分子般細微的尺度

right there on a molecular level,

看出腫瘤的範圍

but you can see it even if it's not right on the top --

即使腫瘤的位置不在最上層一樣看得見

even if it's beyond your field of view.

即使有東西阻隔同樣看得到

And this works for metastatic lymph nodes also.

這項技術也可用在轉移性淋巴結

Sentinel lymph node dissection

前哨性淋巴腺摘除術

has really changed the way that we manage breast cancer, melanoma.

改變了我們治療乳癌、黑色素瘤的方式

Women used to get

過去女性為了

really debilitating surgeries

徹底切除腋下淋巴結

to excise all of the axillary lymph nodes.

必須接受非常折人的手術

But when sentinel lymph node

不過按照我們治療

came into our treatment protocol,

前哨性淋巴結的方法

the surgeon basically looks for the single node

外科醫生會先尋找

that is the first draining lymph node of the cancer.

最早形成腫瘤的淋巴結

And then if that node has cancer,

假如這個淋巴結帶有腫瘤

the woman would go on to get

該名女性病患

the axillary lymph node dissection.

必須接受腋下淋巴結切除術

So what that means

也就是說

is if the lymph node did not have cancer,

假如這個淋巴結沒有腫瘤

the woman would be saved

患者就不必接受

from having unnecessary surgery.

不必要的手術

But sentinel lymph node, the way that we do it today,

現今我們執行的前哨性淋巴腺摘除術

is kind of like having a road map

有點像拿著地圖

just to know where to go.

才知道要往哪邊走

So if you're driving on the freeway

就像你在高速公路上開車

and you want to know where's the next gas station,

想要知道下個加油站在哪

you have a map to tell you that that gas station is down the road.

地圖上顯示往前走就到了

It doesn't tell you whether or not

地圖上不會告訴你

the gas station has gas.

加油站有沒有油

You have to cut it out, bring it back home,

你得把油箱帶回家

cut it up, look inside

打開來看

and say, "Oh yes, it does have gas."

然後才知道：「真的耶，裡面有油。」

So that takes more time.

所以這樣太費時了

Patients are still on the operating room table.

患者仍然躺在手術台

Anesthesiologists, surgeons are waiting around.

麻醉師、外科醫生在一旁等候

That takes time.

要等上一會的時間

So with our technology, we can tell right away.

有了這項技術，我們馬上就可以知道結果

You see a lot of little, roundish bumps there.

這裡有一些小小的、圓圓的腫塊

Some of these are swollen lymph nodes

其中有些是腫大的淋巴結

that look a little larger than others.

看起來比其他的要大

Who amongst us hasn't had swollen lymph nodes with a cold?

在座的各位有誰感冒時不會造成淋巴結腫大？

That doesn't mean that there's cancer inside.

腫大的淋巴結未必代表裡面有腫瘤

Well with our technology,

運用我們的技術

the surgeon is able to tell immediately

外科醫生可以馬上知道

which nodes have cancer.

哪個淋巴結有腫瘤

I won't go into this very much,

細節部分不再多講

but our technology, besides being able

不過這項技術

to tag tumor and metastatic lymph nodes with fluorescence,

除了可以用螢光標記轉移性淋巴結外

we can also use the same smart three-part molecule

我們也可以用相同的三合一分子

to tag gadolinium onto the system

在系統裡標記出釓

so you can do this noninvasively.

如此可以用非入侵方式達到目的

The patient has cancer,

患者患有癌症

you want to know if the lymph nodes have cancer

我們想在手術前

even before you go in.

知道他的淋巴結是否有腫瘤

Well you can see this on an MRI.

可以用核磁共振影像得知

So in surgery,

在手術時

it's important to know what to cut out.

了解切除掉的是什麼東西很重要

But equally important

不過同樣重要的是

is to preserve things

把具有重要功能的組織

that are important for function.

保留下來

So it's very important to avoid inadvertent injury.

所以避免疏忽造成傷害很重要

And what I'm talking about

我這裡所說的是

are nerves.

神經

Nerves, if they are injured,

假如神經受損

can cause paralysis,

可能會造成癱瘓

can cause pain.

造成疼痛

In the setting of prostate cancer,

以前列腺癌來說

up to 60 percent of men

有60%的患者

after prostate cancer surgery

在前列腺癌手術後

may have urinary incontinence

會出現尿失禁

and erectile disfunction.

以及勃起障礙

That's a lot of people to have a lot of problems --

很多的問題發生在很多人的身上

and this is even in

即使是在

so-called nerve-sparing surgery,

所謂的神經保護手術也一樣

which means that the surgeon is aware of the problem,

也就是說外科醫生知道這個問題

and they are trying to avoid the nerves.

並且想辦法避開神經

But you know what, these little nerves are so small,

不過各位知道嗎，和前列腺癌相比

in the context of prostate cancer,

神經非常的纖細

that they are actually never seen.

醫生根本看不見

They are traced

只能透過

just by their known anatomical path

已知的解剖路徑

along vasculature.

沿著血管尋找

And they're known because somebody has decided to study them,

因為有人對此研究，我們才得以知道

which means that we're still learning

也就是說我們仍在研究

about where they are.

神經的位置在哪

Crazy to think that we're having surgery,

很難想像如果我們要動手術切除腫瘤

we're trying to excise cancer, we don't know where the cancer is.

但卻不知道腫瘤在哪

We're trying to preserve nerves; we can't see where they are.

想要保留神經，但卻看不見在哪

So I said, wouldn't it be great

所以我說，如果可以找到方法

if we could find a way

看見發出螢光的神經

to see nerves with fluorescence?

那不是很好嗎？

And at first this didn't get a lot of support.

起先這項研究沒有受到什麼支持

People said, "We've been doing it this way for all these years.

大家都說：「這些年來我們都這樣開刀，

What's the problem?

有什麼問題嗎？

We haven't had that many complications."

我們很少遇到併發症。」

But I went ahead anyway.

不過我執意進行

And Roger helped me.

Roger 協助我

And he brought his whole team with him.

而且他帶著他的團隊

So there's that teamwork thing again.

所以這又是團隊研究

And we eventually discovered molecules

最後我們發現

that were specifically labeling nerves.

可以標記神經的分子

And when we made a solution of this,

當我們做好溶液

tagged with the fluorescence

用螢光作為標記

and injected in the body of a mouse,

把溶液注入老鼠體內

their nerves literally glowed.

神經真的發亮了

You can see where they are.

各位可以看見神經在哪

Here you're looking at a sciatic nerve of a mouse,

現在看到的是老鼠的坐骨神經

and you can see that that big, fat portion you can see very easily.

各位可以很容易的看見大大、肥肥的部分

But in fact, at the tip of that where I'm dissecting now,

實際上，在我正在解剖的位置上

there's actually very fine arborizations

分佈著細微的神經分支

that can't really be seen.

肉眼看不見

You see what looks like little Medusa heads coming out.

看起來就像小小的梅杜莎蛇頭伸出來

We have been able to see nerves

我們可以看見

for facial expression, for facial movement, for breathing --

控制表情、顏面動作和呼吸的神經

every single nerve --

每一條都看得見

nerves for urinary function around the prostate.

前列腺周圍泌尿功能的神經

We've been able to see every single nerve.

我們可以看見每條神經

When we put these two probes together ...

當我們把這兩根探針放一起

So here's a tumor.

看到腫瘤了

Do you guys know where the margins of this tumor is?

各位知道腫瘤的範圍有多大嗎？

Now you do.

這麼大

What about the nerve that's going into this tumor?

那麼腫瘤裡的神經又在哪呢？

That white portion there is easy to see.

白色的部分很容易看見

But what about the part that goes into the tumor?

但是穿進腫瘤的神經在哪呢？

Do you know where it's going?

各位知道神經分布在哪嗎？

Now you do.

這樣子

Basically, we've come up with a way

基本上，我們已經找到

to stain tissue

把組織染色的方法

and color-code the surgical field.

並且在特定區域用顏色作標記

This was a bit of a breakthrough.

這是一項突破

I think that it'll change the way that we do surgery.

我想這會改變目前執行手術的方式

We published our results

我們把結果發布於

in the proceedings of the National Academy of Sciences

美國國家科學院院刊

and in Nature Biotechnology.

以及自然生物科技期刊上

We received commentary in Discover magazine,

發現雜誌和經濟學人雜誌

in The Economist.

對我們的研究作了評論

And we showed it to a lot of my surgical colleagues.

我們把成果拿給很多外科醫生同事看

They said, "Wow!

他們都說：「哇！

I have patients

我的病人

who would benefit from this.

可以因此受惠

I think that this will result in my surgeries

我想這可以為我未來執行的手術

with a better outcome

帶來較好的成效

and fewer complications."

並且減少併發症

What needs to happen now

現在要做的是

is further development of our technology

進一步研究這項技術

along with development

同時研發

of the instrumentation

相關的醫療儀器

that allows us to see

好讓我們可以

this sort of fluorescence in the operating room.

在手術室看見螢光

The eventual goal

最終的目標是

is that we'll get this into patients.

把這項技術用在病患身上

However, we've discovered

然而，我們發現

that there's actually no straightforward mechanism

現在沒有直接可用的裝置

to develop a molecule

可以製作

for one-time use.

供單次使用的分子

Understandably, the majority of the medical industry

我們可以了解，大部分的醫療產業

is focused on multiple-use drugs,

把主力集中在多用途的藥物

such as long-term daily medications.

例如長效性的日服藥物

We are focused on making this technology better.

我們把焦點放在改進技術

We're focused on adding drugs,

添加藥物

adding growth factors,

添加生長因子

killing nerves that are causing problems

殺除有問題的神經

and not the surrounding tissue.

而且不傷害周圍的組織

We know that this can be done and we're committed to doing it.

我們知道這是可行的，所以我們堅決研究

I'd like to leave you with this final thought.

我想把我的感想跟大家分享

Successful innovation

成功的創新

is not a single breakthrough.

並不是單一的突破

It is not a sprint.

不像百米衝刺

It is not an event for the solo runner.

不是單一跑者的比賽

Successful innovation

成功的創新

is a team sport, it's a relay race.

是團隊運動，是接力賽跑

It requires one team for the breakthrough

需要某個團隊先行突破

and another team

另一個團隊

to get the breakthrough accepted and adopted.

把這項突破拿來應用

And this takes the long-term steady courage

這需要長久堅忍不拔的勇氣

of the day-in day-out struggle

日復一日的奮鬥

to educate, to persuade

去教育、說服其他人

and to win acceptance.

以獲得接受

And that is the light that I want to shine

這就是我在健康和醫療

on health and medicine today.

所點亮的一盞燈

Thank you very much.

謝謝各位

(Applause)

（鼓掌）