什麼是腹腔熱化療？
顧名思義，熱化療（溫熱化學治療）就是在提高溫度的狀況下施行化學治療。而腹腔熱化療，就是在腹腔內灌注熱水和化療藥物的狀況下施行腹腔內的化學治療。
甚麼是腹水（ascites）？
在正常情況下，腹腔內會分泌少量液體並且吸收這些少量液體，而達到平衡。平常腹腔內約有50至100毫升（ml）的液體。一旦分泌的速率和吸收的速率無法達到平衡的時候，（譬如分泌的速率大於吸收的速率），這些液體就會堆積，稱為腹水。在很多的腹腔內惡性疾病情況之下，都會導致腹水。
甚麼是腹膜（peritoneum）？
在腹腔內的所有器官（包括胃、大腸、小腸、肝臟、膽囊，膽管，卵巢、子宮、膀胱等等）以及腹壁的表面，都被一層由透明的漿膜所構成很薄的薄膜所覆蓋，稱為腹膜。腹腔內器官的自由移動，藉著腹膜能夠使相互之間幾乎沒有磨擦力。除此之外，腹膜也會分泌及吸收液體。腹膜對於物質在完全溶解的情況之下的吸收，會直接吸收到微血管裡面去，而懸浮在液體的物質則由吞噬細胞的幫忙，帶入淋巴管之中。在腹腔內各不同部位的腹膜對於液體的吸收能力，都不盡相同。一般而言，在上腹部腹膜吸收較快，這是因為上腹部腹腔內器官，表面凹凸不平的面積較大，而且呼吸運動會促進這部位腹膜的吸收能力。腹水內若有懸浮的癌細胞，則被吞噬細胞所吞噬（但不一定死亡），而再被腹膜所吸附卻無法吸收，此時癌細胞便在此處繼續生長而形成腹膜的轉移病灶。
甚麼是腹腔內的化學治療（intraperitoneal chemotherapy）？
傳統的化學治療是將化療藥物打入血管中，藉著血液流經全身而將化療藥物帶到身體各部分去毒殺癌細胞。很不幸的，這種方式有兩個很大的缺點：
一、平常的化學治療，是將化學治療藥物注射到靜脈或動脈內，藥物經由血液循環而流經全身。但是這些藥物穿透腹膜而達到腹腔內的濃度卻少之又少。化療藥物流經全身而產生的副作用很明顯，導致病人的不適。若要讓化學治療藥物穿透腹膜而達到腹腔內的濃度提高，必須同時提高靜脈注射（或動脈注射）的藥物濃度。如此造成的全身性副作用太大，人體會受不了。
二、化療藥物進入到腹腔的濃度很低，一旦癌細胞進入到腹腔中，傳統方式的化學治療效果就很不理想。腹腔內腹膜轉移的每一個癌病灶，只有一小部分附著於腹膜上，大部分都暴露於腹腔內，是化學治療藥物到達不到的地方。
在消化道的癌症（例如：胃癌、小腸癌、大腸癌、直腸癌、闌尾癌、膽囊癌以及胰臟癌）及卵巢癌、子宮內膜癌等，癌細胞跑到腹腔內是一種很常見的現象。也就是說，在這些癌症一旦產生腹腔內的腹膜轉移時，單純的傳統化學治療將得不到預期的效果。
因此，必須經由特殊的途徑，將化學治療藥物直接注射到腹腔內，稱為腹腔內的化學治療。因為藥物直接注射到腹腔內，因此腹腔內的藥物濃度相當高，毒殺癌細胞的效果很好。另一方面，雖然腹腔內的藥物濃度相當高，但是經由腹膜吸收到血液循環的部分卻相當少，而造成全身的副作用也很少。對於腹腔內腹膜轉移的癌病灶，利用腹腔內的化學治療，是一種相當理想的方式。
那爲什麼很少聽說呢？又爲什麼平常腫瘤科醫師不用呢？
因為腹腔內的化學治療必須面對的問題有：
第一、經由什麼途徑給予藥物？必須利用手術的方式來做出這個途徑。
第二、藥物在腹腔內是否可以平均分佈？一般是不可能的，必須利用手術的方式在腹腔內用人為的方式來達到藥物平均分佈（例如攪拌）。
第三、藥物對於癌病灶的穿透能力有限，一般不會超過1或2mm。若癌病灶的體積超過2mm，則藥物殺死癌病灶的能力就有限。因此必須先將較大的癌病灶利用手術方式除去，就是所謂的腫瘤減量手術及腹膜剝離術。
第四、考慮到不易切除的病灶，希望加強腹腔內化學治療藥物殺死癌病灶的能力，就必須使用加熱治療的方式。在加熱的情況下，化學治療藥物穿透癌病灶的能力，將增加到2–5mm。
由此可知，腹腔內的化學治療必須經由手術的方式來達成，也就是說必須由外科醫師來施行。但是了解腹腔內化學治療的方式及方法的外科醫師相當少，懂得施行腫瘤減量手術及腹膜剝離術以及熱化療的醫師更少，而且有熱化療設備的醫院更少，最後的結果是，有能力施行腹腔內的化學治療的醫師人數寥寥可數。
我在這裡提出這個觀念，希望多數外科醫師及腫瘤科醫師爲病患著想。當病患還有機會施行這樣的合併治療方式時，不妨請病患家屬前來諮詢。
如果您是病患或家屬，請和我們預約前來諮詢。
為什麼要加熱？
熱療法對於腹腔內腹膜的腫瘤或者癌症轉移的治療有很多好處。
一、某些化療藥物在溫度提高時會增加藥物對癌細胞的毒殺能力。
二、提高溫度能夠增加化學治療藥物對組織的穿透能力。
三、溫度提高時能殺死癌細胞（因為癌細胞比正常細胞不耐熱!!!）
手術中腹腔內熱化療是指在手術當中在腹腔內給予加熱的化學治療。這樣可以讓我們在腹腔內使用非常高濃度的某些化學治療藥物，這些藥物就會在腹腔內腹膜的表面直接與遺留下來的腫瘤細胞發生反應，而殺死這些癌細胞。在提高溫度及提高化療藥物濃度的狀況下，殺死癌細胞的能力將大大的提升。如果我們不在手術當中施行，而是在手術後好幾天甚至在好幾個月以後才施行，這些藥物會因為腹腔內發生黏連，而無法充分與遺留下的腫瘤的細胞發生反應。（但是我們目前仍然可以利用合併其他治療方式達到術前或術後的腹腔內化療）
最近有愈來愈多的臨床研究投入熱療法的領域之內，已使得熱療法定位於除了手術、化學治療、放射治療、標靶治療，免疫療法之外的「第六種」癌治療法。雖然在醫學圈內，熱療法的成效已經慢慢的被接受，然而仍然有許多醫學界的人士對於熱療法感到陌生。
這裡所稱的熱療法並非一般坊間所稱的熱療(例如非侵襲性的遠紅外線)，而是高侵襲性的腹腔內熱療法。熱療法目前並沒有統一的名詞，最常稱為hyperthermia，但是這樣很籠統，應該再加註方式，例如regional（局部性），systemic（全身性），intraperitoneal（腹腔內），intraoperative（手術中），以及是否合併chemotherapy（化學治療）。因此美國華盛頓DC 的Medstar Hospital的Sugarbaker醫師（腹腔熱化療的先鋒）以前喜歡稱為 Heated Intraoperative Intraperitoneal Chemotherapy（簡稱HIIC），有人喜歡稱為 hyperthermo-chemotherapy，日本則普遍稱為 Continuous Hyperthermic Peritoneal Perfusion（簡稱CHPP），或稱為 Chemo-hyperthermic Peritoneal Perfusion（還是簡稱CHPP），有人就乾脆分開稱為intraoperative intraperitoneal hyperthermia with chemotherapy。在中國大陸則稱為熱灌注治療，或灌注熱療（參考http://www.cnhan.com/big5/content/2003-04/12/content_261913.htm）。
HIPEC（Hyperthermic Intraperitoneal Chemotherapy）是目前腹腔熱化療的統一名稱，於專業醫療期刊進行搜索HIPEC時，可發現大量發表的論文。
HIPEC的治療對象是腹腔內腹膜表面廣泛瀰漫性的癌轉移，目前也只有這個治療方式。對於深層的局部侵犯性癌症，例如前列腺癌、膀胱癌、子宮頸癌等等，則必須利用深部電磁波的聚焦加熱來治療，請參考萬芳醫院熱療中心的BSD-2000。
熱療法如何治療癌症？
在正常的人體組織中，當局部或全身的溫度提高時，會引起身體的一些正常生理反應，包括微血管擴張、呼吸加快、心跳加快、心搏量增加、腎臟製造尿液增加。這樣的作用，是為了要散熱。另一方面，由於溫度提高時造成細胞的新陳代謝加快，細胞對於氧氣的需求增加，消耗細胞內的能量（由ATP供給），而且新陳代謝加快所製造的細胞廢物排出量也增加。這些細胞生理的改變，都可藉由上述的身體正常生理反應來解決。因此正常的人體組織中，因為體溫提高而受到的傷害就不明顯了。
但是癌症在局部或全身的溫度提高時，造成的影響就不同了。一般癌症的癌細胞都很密集的緊靠在一起，而最重要的是，癌症的血管分佈並不像正常人體組織中的微血管分佈。因此當溫度提高時，造成它內部血液循環的改變並不明顯，它的微血管散熱效率也很差。
利用這樣的一種差別反應，當溫度提高的時間持續一個小時以上時，正常的人體組織因為有效率的散熱作用，溫度並不會提高很多，但是癌症的散熱效率不佳，因此癌症內部的溫度會持續提升。當溫度提升到達一個程度時，癌細胞就因為氧氣供給量不夠、廢物堆積細胞內、能量製造不及，再加上蛋白質變性、DNA和RNA破壞，造成癌細胞相繼死亡。
What is HIPEC (hyperthermic intraperitoneal chemotherapy)?
Hyperthermic chemotherapy, is a chemotherapy performed under elevated temperature. HIPEC, is a chemotherapy performed within the peritoneal cavity under elevated temperature, by adding heated solution and chemotherapeutic agents.
What is ascites?
In normal condition, the abdominal cavity creates (secrets) a little amount of fluid and absorbs it, makes a balance. Usually, there are 50ml to 100ml of fluid in the abdominal cavity. If there can not reach a balance, for example, secretion is faster than absorption, the fluid accumulates and forms ascites. Many different intra-abdominal cancers all cause ascites.
What is peritoneum?
All organs within the abdominal cavity (also called peritoneal cavity) including the stomach, colon, small bowel, liver, gallbladder, bile duct, ovary, uterus, urinary bladder and the surface of the abdominal wall, are covered by a thin layer of serosa tissue, we call it peritoneum. The visceral peritoneum covers the organs, and the parietal peritoneum covers the abdominal wall. Because this peritoneum, the organs move between each other without resistance. The peritoneum absorbs fluid and substances in fluid, and also secrete fluid. The substance dissolved in the fluid can be absorbed by the peritoneum and into the small blood vessels (capillaries), but the substance that can not be dissolved in the fluid is “swallowed” by phagocytes and then bring into the lymphatics. The capability of absorption by peritoneum differs in different part of peritoneum. Usually, the absorption is fast in the upper abdomen due to large area of organ surface and the respiratory movement. In case there are floating cancer cells within the ascites, they are “swallowed” by phagocytes (but usually not dead) and then were attached at the surface of the peritoneum. Then cancer cells grow here and form peritoneal metastasis.
What is intraperitoneal chemotherapy?
Usually, we give chemotherapy drugs into the blood vessels (systemic chemotherapy), and the drugs were brought by blood stream and distributed to every part of the body. Unfortunately, there are two major unwanted defects.
1, The chemotherapy drugs go with blood to the whole body, but its penetration through the peritoneum into the peritoneal cavity is very poor. The side effects caused by systemic chemotherapy are significant, and caused patient discomfort. In order to raise the drug concentration within the peritoneal cavity, we need higher drug dosage and higher drug concentration within the blood. Consequently, it causes more significant side effects to the patients. Patients can not tolerate the significant side effects under such a high dose of chemotherapy.
2. Since the drug concentration is low within the peritoneal cavity, once there are cancer cells within the peritoneal cavity, the cancer treatment result is poor. The cancers metastasize to the peritoneal cavity usually attach to the peritoneum, and expose most of the metastatic surface into the peritoneal cavity – that chemotherapy drugs can not reach.
Cancer cells metastasis within the peritoneal cavity (peritoneal metastasis) is frequently seen by digestive tract cancers (such as gastric cancer, small intestinal cancer, colon cancer, rectal cancer, appendiceal cancer, gallbladder cancer, pancreatric cancer) and ovarian cancer, endometrial cancer. In this condition, the results by conventional systemic chemotherapy are very poor.
Through a specific pathway, we deliver the chemotherapy drugs into the peritoneal cavity. We call it intraperitoneal chemotherapy. Because the drugs are injected into the peritoneal cavity directly, the drug concentration within the peritoneal cavity is very high. It means the drugs kill cancer cells effectively. At the same time, the drugs are absorbed through the peritoneum into the blood stream slowly. The drug concentration within the blood is very low and causes only slightly systemic side effects. By this way, intraperitoneal chemotherapy is considered as an ideal method to treat cancers with peritoneal metastasis.
Why intraperitoneal chemotherapy is not frequently applied by medical oncologists?
There are some difficulties when dealing with intraperitoneal chemotherapy.
1. The route of drug administration. The route is usually created by a surgical method.
2. Usually the drugs can not be distributed evenly within the peritoneal cavity. We need to make its distribution evenly, usually by manual method during the operation.
3. The drug penetration into the cancer site is still limited. Usually the depth of drug penetration is within 1-2mm. If the metastatic cancer lesion is larger than 2mm, the killing effect by drugs is limited. We need to remove large metastatic lesions by surgical method, the so called cytoreduction surgery and peritonectomy.
4. However, if the metastatic cancer lesions are located at a difficult site (i.e. very difficult to remove it by surgical method), we need to enhance the drug killing effect, by heating the intraperitoneal fluid. Under heating condition, the depth of drug penetration can be enhanced to 3-5mm.
Eventually, intraperitoneal chemotherapy must be performed by a surgical method, and by surgeons. However, there are only a few surgeons understanding intraperitoneal chemotherapy, cytoreduction surgery and peritonectomy. Furthermore, there are only few hospitals own heating equipment. In many conditions, we need multimodality of cancer treatment, cooperated by surgeons and medical oncologists. In some selected cases, the peritoneal metastasis can be effectively treated.
Why treatment in heating ?
There are many benefits using elevated temperature to treat peritoneal tumors or peritoneal metastatic cancers.
1. Some chemotherapeutic agents kill cancer cells more efficiently in higher temperature than in normal temperature.
2. The chemotherapeutic agents penetrate tissue deeper in higher temperature than in normal temperature.
3. Elevated temperature kills cancer cells (cancer cells are heat-intolerance).
HIPEC treats cancers during the operation, in the peritoneal cavity, using heated solution with chemotherapy drugs. By this method, we can use high concentration of chemotherapy drugs to kill cancer cells. Under the conditions of elevated temperature and increased drug concentration, the killing effect to cancer cells will be significantly enhanced. Instead of intraoperative HIPEC, if we perform HIPEC at several days after the operation, there will be intraperitoneal adhesions that prevent direct effect between chemotherapy drugs and cancer cells (though we can still apply intraperitoneal chemotherapy before or after operations using some combined methods).
Recently, there are more and more heating treatments applied to cancer therapies, and becomes a cancer therapy beside surgery, chemotherapy, radiotherapy, target therapy and immunotherapy. Heat therapy is gradually accepted in a medical field, however, it is still not well understood by many physicians.
The intraperitoneal heat treatment (hyperthermic treatment) is different from the usual heating that causes warming effect only, such as infrared. Previously, it was called hyperthermia, and could be regional, systemic, intraperitoneal, intraoperative, or even combined with chemotherapy. Dr. Sugarbaker (Medstar Hospital, Washington D.C.), a pioneer of HIPEC, used to call it Heated Intraoperative Intraperitoneal Chemotherapy (HIIC), or hyperthermo-chemotherapy. In Japan, it was called CHPP (Continuous Hyperthermic Peritoneal Perfusion, or Chemo-hyperthermic Peritoneal Perfusion). No matter what we called it, it is a procedure of intraoperative intraperitoneal hyperthermia with chemotherapy.
Now, the term HIPEC (Hyperthermic IntraPeritoneal Chemotherapy), is accepted worldwide and is indexed in the medical journals.
Within the abdominal cavity, the tumors located at the peritoneal surface, can be treated by HIPEC, and is the only effective method at the present except surgical resection. Other locally deep seated invasive tumors, such as cancers of prostate, urinary bladder, uterine cervix, can not be treated by HIPEC, and must be managed by other type of heating. BSD-2000 in Wan-Fang Hospital is utilized for these types of malignancies.
How does heat treat cancers?
In human body, there will be some responses when temperature is elevated, such as dilatation of capillaries, increasing breathing rate, increasing heart rate, and increasing cardiac pumping volumes in order to dissipate the heat. At the same time, the elevated temperature causes increased intracellular metabolism, increased cellular demand of oxygen, and depletion of cellular energy (which is supplied by ATP), increased amount of intracellular metabolic wastes. These cellular physiological changes are usually handled by normal human body physiological changes.
However, the responses to elevated temperature in cancer tissues are not so efficiently as in normal human tissues. The blood vessel distributions in cancer tissues are not well organized, and there will be no significant change on blood circulation. This causes heat dissipation is poorer in cancer tissue than in normal human tissue.
As a result, when there is only mild elevation of temperature, and when it persists for a period of time (for example, 60 minutes), the heat is accumulated in cancer tissue, but is dissipated in normal human tissue. The temperature in cancer tissue will be higher than in normal human tissue. The oxygen and energy in cancer cells are depleted, the metabolic wastes are accumulated in the cancer cells, make acidity of microenvironment, protein denaturization, DNA and RNA destruction, and finally causing cell death.
什麼樣的腫瘤可以用熱療法來治療？
理論上，只要是對溫度有反應的腫瘤都可以用熱療法來治療。但請勿誤解，如果可以用手術切除的腫瘤仍然是以外科手術切除為主。只有一些無法切除或是腫瘤部位不適合切除時，才考慮以熱療法來治療。因此，不論是腦部、骨頭、咽喉、甲狀腺、肺、乳房、肝臟、胰臟、大腸、胃、卵巢、子宮、前列腺及皮膚，只要有適當的加熱方式，都可以用熱療法來治療。
然而實際上因為技術性的關係，上列的這些癌症可能必須利用不同的加熱方式來施行熱療法。
已經使用熱療法，為何還要使用化學治療？
熱能本身便能造成腫瘤細胞的破壞與壞死。然而從更多的醫學研究中得知，當熱療法合併其他的治療方式時（例如化學治療或放射治療），對於腫瘤細胞的治療結果將大大的提升（不只相加的作用而已）。更有研究報告指出，若利用熱療法合併化學治療或放射治療，對某些腫瘤的治療反應可以達到二倍到三倍。
在治療癌腫瘤的過程，何時是使用熱療法的適當時機？
與其他的癌症治療一樣，熱療法應該愈早開始愈好，以免腫瘤對身體產生太多的破壞作用。以胃癌而言，目前萬芳醫院對於胃癌以手術切除原發病灶以後，便立即施行腹腔內的熱化療以治療轉移的腫瘤。
對於一些已經知道非常嚴重的腹腔轉移病患，可以在手術前先給予新輔助性的腹腔熱化療，再接著後續化療，待腫瘤被控制變小後再進行手術切除，再給予一次腹腔熱化療，也是一個可以考慮的方式。
因為觀念的改變，對於雖然沒有肉眼可見的轉移病灶，然而知道有癌轉移的高危險因素時，給予預防行的腹腔熱化療，目前也是可以考慮的一個時機。
接受腹腔熱化療的病患有沒有任何限制條件？
對於局部施行的熱療法，比較沒有限制條件。但是對於會影響到全身性的熱療法，例如利用體外循環的熱灌注治療，或者萬芳醫院目前施行的腹腔內熱化療法，會影響體溫的升高、心跳加快、尿排出量增加，則限制病患的心肺功能及腎臟功能都必須在一定的程度以上。然而隨著社會及醫療的進步，年齡已經比較不是重要關鍵，而是要評估日常活動能力及心肺功能。
不論是哪一種的熱療法，目前都仍然不建議使用在兒童身上。如果有其必要性， 必須要有更嚴格的評估條件。
腹腔熱化療通常約需住院多久？
依各種不同的癌症，不同方式的熱療法，會有不同的療程。以萬芳醫院目前施行的腹腔內熱化療法為例，通常在手術中施行，手術後視狀況，有些病患必須立即配合施行腹腔內的化學治療。因此單是手術的恢復療程就需要五至七天。再加上複雜的手術以及腹腔熱化療的影響，全部住院日數則視病患手術後的恢復狀況而定，一般而言約需二週至三週。萬一手術後發生併發症，則視併發症的嚴重程度而無法預先估計何時可以出院。
目前因為腹腔熱化療的發展已經進步到多元化，甚至有些病患只需要接受單純的腹腔鏡腹腔熱化療，恢復也相當快，一般都在五天之內可以出院。
熱療法會改變體內的免疫反應嗎？
局部的熱療法，到目前為止並沒有可靠的醫學證據顯示會破壞體內的免疫反應。但是以萬芳醫院目前施行的腹腔內熱化療法而言，在施行的過程中的確會有一些免疫細胞會被破壞，但破壞程度有限，我們也會嚴密監控並給予矯正。相反的，在治療之後反而會刺激體內的免疫反應。至於手術後所引起的抵抗力不佳或白血球數下降，則是和化學治療有關，不是熱療法所引起的。
到底熱療法的溫度有多高？
一般我們不能利用太高的溫度來治療，否則容易引起身體正常組織的壞死。但是我們可以利用持續的加熱時間來造成腫瘤細胞與正常組織之間的溫度差，而造成腫瘤的壞死（請參考之前的章節）。在萬芳醫院最常利用的溫度是攝氏42到43度之間，持續一個小時到二個小時。因為病患是在全身麻醉的狀況下接受腹腔內熱化療法，因此不論是加熱引起的或化療引起的，都不會感覺到有任何痛苦。
腫瘤減量手術（cytoreduction surgery）
腫瘤減量手術是指在腹腔內的腹膜表面積極的去除，或者破壞所有肉眼可見的腫瘤。我們可以利用一些外科手術的技術，而達到去除或破壞這些腫瘤。例如用雷射光、超音波刀，以及傳統手術等等。病患經過腫瘤減量手術後的長期結果，與外科醫師是否有能力除去所有肉眼可見的腫瘤程度有關。因此腫瘤減量手術後的長期好處，是直接與腹腔內遺留下來的腫瘤體積有關係。在腹腔內所遺留下腫瘤體積越小，則這些腫瘤對於後續的腹腔熱化療反應越好。腫瘤減量手術是一個牽涉範圍很廣泛，很積極而且很耗時的手術過程，通常都需要超過十個小時。不但如此，我們還常常需要拿掉部分的小腸、部分的大腸以及脾臟、胃、膽和部分的胰臟，介此達到細胞減量，甚至必須施行暫時性的人工肛門。因為手術的複雜程度高且耗費時間、耗費醫師體力，也耗費病人體力，而且必須在手術結束前立即施行腹腔熱化療，因此手術後的併發症比例也比一般手術高。因為複雜程度高，因此並非所有的外科醫師都有能力處理，也不願意處理。至於手術的範圍，將決定於腫瘤的位置體積，以及考慮到術後病人的生活品質而作決定。
腹膜的癌轉移（peritoneal metastasis）
腹膜的癌轉移是指癌細胞從原發的癌部位脫離而掉入腹腔內。這些癌細胞有部份仍維持在游離狀態，而有一部分接觸到腹膜而附著在腹膜而繼續生長。一開始這些腫瘤細胞不直接侵犯一些實質的器官例如肝臟、脾臟、子宮及卵巢。一旦時間久了，也會慢慢長大而直接侵犯進入（長入）這些器官。這種現象在腹腔內的消化道的癌症（例如：胃癌、小腸癌、大腸癌、直腸癌、闌尾癌、胰臟癌、膽囊癌）以及卵巢癌、子宮內膜癌，是一種很常見的現象。當然也有很少數的癌細胞就起源於腹膜本身，這種情況稱為原發性腹膜表面癌症。
雖然腹腔內腹膜的癌轉移是一種預後非常不佳的轉移型式，但是它可能只是侷限在腹腔內腹膜的表面而已，可以視為區域性的轉移而非全身性的轉移，因此還有機會利用手術的方式去除這些肉眼可見的癌細胞。
以往腹腔內的癌轉移被認為是一種癌症末期的表現方式，因此絕大部分的腫瘤科醫師都只是給予一個輔助性或支持性的治療而已。這些病人大部分都會出現腹水囤積，以及腸阻塞的現象，而導致不堪的疼痛及饑餓狀態。如果沒有給予積極性的治療，這些病人被診斷出有腹腔內腹膜的癌轉移的時候，都剩下幾個月的存活時間而已。在我們的經驗裡面，這樣的病人存活時間都小於六到七個月，一般而言都只有三個月。積極性腫瘤減量手術，不論是否後續給予化學治療，都顯示出對於這些病人有好處。
在1980年代開始施行腹腔內的化學治療，並且在一些病人身上顯示成果。目前這樣的治療方式在全世界許多醫學中心正在嘗試著。甚至在手術當中給予手術中腹腔熱化療，更提供了病人另外一種治療方式。不但如此，再加上腹膜剝離手術以及手術後腹腔內的化學治療，更可以讓一些病人達到長期存活的狀況。我們曾經使用這樣的方式治療一些被認為是末期的病人，而目前這些病人都無復發的跡象。雖然這種合併的治療方式是非常積極的而且有高危險性的，但是經過適當評估及術前準備以後，多數病人都能夠承受起這些合併治療的步驟。雖然仍然有一些手術引起的併發症，但是都可以經由特殊的外科醫師來處理這些併發狀況。
致於使用何種藥物將依腹腔內的腫瘤形態來決定。在術後的追蹤上，生活品質的研究顯示，有大部分的人都可以恢復到日常生活，甚至有許多病人可以回到工作崗位，有些病患甚至達到長期的存活。
腹膜剝離術（peritonectomy）
這是屬於腫瘤減量手術的一部份。按照字面翻譯，應該稱為腹膜切除手術。對於腹腔內腹膜轉移的癌病灶，數量通常不只一個，因此不太可能一個一個的個別切除，況且尚有許多肉眼看不到的微小癌病灶存在於腹膜表面上。要儘量除去這些轉移的癌病灶，就需要將受到影響的腹膜一整片切除，稱為腹膜剝離術。我們並不稱為腹膜切除手術，是因為腹膜在腹腔內所覆蓋的面積太廣泛，幾乎包含所有的腹腔內器官，有些地方是不可能單純將腹膜剝離出來（必須連同器官一起切除，例如腸道，卵巢，子宮等）。假若所有腸道都被轉移的癌症侵犯時，因為我們不可能將所由腸子切除，勢必將無法達到理想的腫瘤減量手術。
那麼剩下來在腹腔內的許多肉眼看不到的微小癌病灶或甚至必須顯微鏡才看得見的癌細胞將如何處理呢？我們就必須利用手術中腹腔熱化療來殺死這些微小的癌病灶。
腹腔內的播種式轉移
經由腹腔內類似播種方式的轉移稱為腹腔內的腹膜轉移，或者是腹膜的癌轉移。我們想像，用手指在一片烤過的吐司的表面摩擦，會有吐司的屑屑掉落到地面上。這就好像癌症的表面與腹腔內的其他器官摩擦時，會有癌細胞掉落到腹腔內，與腹膜接觸、附著、生長，因此數量通常不只一個。
經由血液的擴散通常是一種很嚴重的轉移方式，因為它代表著一種全身轉移的狀態，不是利用手術就可以治癒這個疾病。
經由腹腔內的腹膜轉移，以往認為也是一種很嚴重的轉移方式，因為轉移的範圍太廣泛，通常外科醫師都會放棄而採取消極或姑息的治療方式。要完全除去這些腹腔內腹膜轉移的癌細胞是不太可能的，因為一方面要切除很多的組織，另一方面對於存在的微小癌細胞（肉眼看不到的）也無法消除。但是目前我們可以利用腹膜剝離術、腫瘤減量手術以及手術中腹腔熱化療的合併方式，來達到治療的目的。
熱化療也可以應用在胸腔嗎？
是的，我們也使用在胸腔中，或稱為肋膜腔熱化療。它可使用在肋膜間皮瘤、甲狀腺癌，或少部分的肺癌。另外，當其他癌症轉移至肋膜腔(而不是肺)時，會引起肋膜腔積水，稱為肋膜腔的惡性積水。目前我們只使用在治療其他癌症轉移到肋膜腔而引起肋膜腔的惡性積水，而且合併胸腔內的腫瘤減量手術，初步的成績不輸給腹腔熱化療。目前並沒有一個統一的名稱，姑且先稱為胸腔熱化療。因為我們對於腹腔間皮瘤的治療效果佳，我們相信對於肋膜腔的間皮瘤治療效果應該也可以期待。
What cancers can be treated by hyperthermia?
Theoretically, any solid malignant tumors responsive to heat can be treated by hyperthermia. However, if surgical removal is feasible, it should be treated by surgical resection. Hyperthermic therapy should be reserved for those cancers that surgical resection is impossible. Malignant tumors involving the brain, bone, throat, thyroid, lung, liver, pancreas, colon, stomach, ovary, uterus, prostate and skin, if only there is an adequate method, can be treated by hyperthermic therapy.
Due to technical reasons, the above mentioned malignant tumor should be treated by different methods of hyperthermic therapy.
Why we still need chemotherapy in addition to hyperthermic therapy?
Heat per se causes tumor destruction and necrosis. Many medical researches indicate that, when combining hyperthermic therapy (such as chemotherapy or radiotherapy), the treatment effect will be enhanced significantly. Furthermore, up to two or three folds of therapeutic effect is seen by chemotherapy with hyperthermia.
When should be hyperthermic therapy applied during cancer treatment?
It is the same as usual cancer treatment, hyperthermic therapy should be initiated as early as possible. For gastric cancer as an instance in Wan-Fang Hospital, we performed radical gastrectomy first and then followed by HIPEC immediately to treat the metastatic peritoneal lesions.
Sometimes, we performed a neoadjuvant HIPEC (HIPEC before surgery) first, followed by scheduled chemotherapy (either systemic or intraperitoneal chemotherapy). After the cancer shrink to some degree, then surgery was performed with HIPEC again. It is now considered as an alternative method for some cases with far advanced intraperitoneal metastasis.
As the concept changes with time, in those cases with high risk of peritoneal metastasis, we gave prophylactic HIPEC.
Are there any patient selection criteria to receive hyperthermic therapy?
There is no specific limitations to those received local hyperthermic therapy. However, if the hyperthermic therapy that will change the systemic reaction, such as extracorporeal hyperthermic perfusion, or HIPEC in Wan-Fang Hospital, will causes rise of body temperature, increasing heart beats, and increasing urine output. We will evaluate the heart, lung and renal functions as well as usual daily activities.
Children is not suggested for hyperthermic therapy at the present. If needed, it should be critically evaluated.
How many days of hospital stay after HIPEC?
It depends on different cancers and different hyperthermic method. At Wan-Fang Hospital, HIPEC is usually performed during the operation. Some selected cases with receive intraperitoneal chemotherapy immediately after surgery. In a simple case, the hospital stay will be 5 to 7 days for recovery. However, most of the cases are complicated, received complicated surgical procedures, and need longer postoperative hospital stay. It may need two to three weeks for recovery staying in the hospital. If any complication developed after the surgery, the hospital stay will by much longer.
We now performing different kinds of hyperthermic therapies. For laparoscopic HIPEC, the postoperative recovery is very soon and the hospital stay is usually shorter than 5 days.
Will hyperthermic therapy change our immune responses?
There is no any medical evidence of changes in immune response caused by local hyperthermic therapy. HIPEC in Wan-Fang Hospital, will cause limited destruction of immune cells. We always keep monitoring it and correct it if indicated. On the contrary, elevated temperature will enhance immune response. Leukopenia after HIPEC is caused by chemotherapy, not by HIPEC.
What is the temperature for hyperthermic therapy?
The temperature applied for hyperthermic therapy can not be too high. High temperature also causes human tissue necrosis. We apply a persisted moderate-high temperature. That will cause a temperature difference between the cancer cells and normal tissue and consequently causing cancer necrosis (please refer to a previous section). In Wan-Fang Hospital, we use HIPEC at a temperature between 42 to 43°C and keep it for one to two hours. The patient receives HIPEC under general anesthesia and feels no pain at all.
Cytoreduction Surgery
Cytoreduction surgery is a term describing aggressive removal or destruction of visible tumors. We use different devices and techniques to perform it, including SonoSurg®, Ligasure®, or argon beam laser. The surgical result is closely related to the completeness of cytoreduction. The smaller tumors remaining after cytoreduction surgery, the better response to HIPEC. For advanced peritoneal metastasis, cytoreduction surgery is a complicated surgery and a time-consuming surgery. It usually takes more than 10 hours. Sometimes, we need to remove a part of small intestine, colon or rectum, stomach, spleen, and many other intraperitoneal organs, even to create a colostomy or intestinal ostomy, in order to complete a cytoreduction surgery. HIPEC (causes some degree of tissue burn injury) will be applied immediately after cytoreduction surgery during the operation. All these conditions cause patient weakness and the postoperative complication rate is usually higher than the usual major surgeries. This complicated as well as high risk surgery also causes surgeons exhausted after surgery. This may explain why there are only few surgeons will (and can) do the surgery. The extent of surgery will be depended on the tumor location, extensiveness, and postoperative life quality.
Peritoneal Metastasis
In some occasions, cancer cells within the peritoneal cavity do not invade into the intra-peritoneal solid organs at the beginning. They detach from the primary cancer site and drop into the peritoneal cavity. Some keep freely in the peritoneal cavity, and some attach to the peritoneum, grow on peritoneum and keep progression. After a period of time, these cancers also invade into these solid organs. In cancers originated from the digestive tract (such as the stomach, small intestine, colon, rectum, appendix, pancreas, gallbladder), ovary and endometrium, peritoneal metastasis is very common. Some cancers originated from the peritoneum per se, and is called primary peritoneal cancer.
The prognosis of peritoneal metastasis is very poor. However, it probably is limited within the peritoneal cavity, and invades peritoneal surface only. In this situation, I is a kind of regional metastasis, not a systemic metastasis. It is the reason why it can be treated by surgical methods to remove the gross (macroscopic) tumors.
In the past, peritoneal metastasis was considered as a terminal stage and most oncologists gave supportive treatment only. These patients appeared as ascites, intestinal obstruction, starvation and abdominal pain. If not treated appropriately, patients diagnosed as peritoneal metastasis, usually died within a short time. In our experiences, there were 6 to 7 months to live, usually 3 months only. Aggressive cytoreduction surgery (CRS) revealed its benefits in these patients, no matter following chemotherapy or not.
Intraperitoneal (IP) chemotherapy was started since 1980s and revealed positive results in some patients. Nowadays, many medical centers are doing IP chemotherapy in the world. HIPEC performed during operation, is a kind of IP chemotherapy. We treated some “terminal” patients by CRS plus peritonectomy plus HIPEC plus postoperative IP chemotherapy with encouraging results. Some of these patients survived for many years, and some even without any evidence of recurrence.
This is an aggressive and combined treatment method, though with high risk, most of the patients can tolerate it with adequate evaluation and preoperative preparations. Though there were still surgical complications, most of them could be managed by surgeons.
The applied chemotherapeutic drugs depend on the cancer types. In the follow up of life quality, most of these patients returned to their daily activities, some of them even returned to their works. Some of these patients get long term survived.
Peritonectomy
Peritonectomy is a part of cytoreduction surgery (CRS), it means removal of the peritoneum. There are usually multiple intra-peritoneal metastatic lesions, attaching on the surface of the peritoneum, sometimes hundreds. It is very difficult and impossible to remove them one by one. Furthermore, there are still multiple microscopic metastatic lesions attaching on the peritoneum. To remove them as possible, it is better to remove them with the peritoneum together, the so called “peritonectomy”. The peritoneum covers the whole peritoneal cavity, including the whole surface of the intra-peritoneal organs. If the metastatic lesion invades into the organ, especially the intestines, we have to remove them with resection of the intestines. If all the intestines are involved by the metastatic lesions, since it is impossible to remove all of the intestines, we can not achieve an adequate cytoreduction.
The remaining microscopic cancer lesions, since we can not see them, so we can not (do not know where to) remove them. Fortunately, these microscopic lesions can be treated by HIPEC.
Seeding of intra-peritoneal metastasis
Cancer cells detach and drop away from the primary cancer site when they contact and rub with other intra-peritoneal organs. Those detached cancer cells drop to everywhere within the peritoneal cavity, implant to the peritoneum and then start to grow, progress to form another significant cancer lesion. This way of cancer spreading is just like seeding and we call it peritoneal seeding.
Sometimes, cancers metastasize to other place through blood stream, the so called hematogenous metastasis. Hematogenous metastasis is considered as a systemic metastasis and the prognosis is poor, because it is impossible to cure it by surgical resection.
Peritoneal seeding was considered impossible to cure, because it involved diffuse peritoneal surface, and in many occasions the surgeons will give up surgical removal of the cancers. It was impossible to remove all of the cancers and was impossible to eradicate the microscopic cancers. However, now we combine cytoreduction surgery(CRS), peritonectomy and HIPEC to approach the intent of cure.
Can hyperthermic chemotherapy also applied in chest cavity?
Yes, we also applied it to the chest cavity (thoracic cavity, pleural cavity). It can be applied to treat pleural mesothelioma, thyroid cancer, and a small portion of lung cancer. In addition, when cancers originated from other sites metastasis to the pleural cavity (but not lung), it will cause pleural effusion. It is the so-called malignant pleural effusion. At the present, we only applied it to treat the malignant pleural effusion after intra-thoracic CRS. The initial result is comparable to HIPEC. There is no unique term for it, and now we call it HITHOC (Hyperthermic Intra-Thoracic Chemotherapy). As we treated peritoneal mesothelioma with a good result, we can also expect the good result from pleural mesothelioma.