Complete surgical excision represents the most effective therapy for most solid tumors. Despite tremendous efforts and legitimate advances in cancer treatment with drugs, radiation, and biological response modifiers, the majority of patients with solod tumors will have benefited from surgery alone.

How to treat called unresectable cancer? Proper strategy are application of new high-technical, especially minimally invasive modalities, combination of high-technical modalities and traditional modalities (operation, radiation and chemotherapy), and integration of traditional Chinese medicine and modern medicine.

NEW HIGH-TECH THERAPIES

Currently there are a lot of new high-tech modalities for cancer treatment (table 1). They may offer an option for treating cancers that are considered inoperatable or that do not respond to standard treatments.

COMMENT
Our experiences show that cryosurgery offers some advantages over other methods of cancer treatment:

It is less invasive than surgery, involving only a small incision or insertion of the cryoprobe through the skin. Consequently, pain, bleeding, and other complications of surgery are minimized.

Because physicians can focus cryosurgical treatment on a limited area, they can avoid the destruction of nearby healthy tissue. This is of particular importance to patients with hepatocellular carcinoma, because the majority of these patients have cirrhosis and compromised liver functions. By sparing more "normal" liver, the patients will have greater liver reserve.

The treatment can be safely repeated and may be used along with standard treatments such as surgery, chemotherapy, and radiation.

Because of the warming effect of flowing blood, large blood vessels, such as the inferior vena cava and portal vein, are somewhat impervious to the effect of freezing. Hence, tumors close to these venous systems can be treated with cryosurgery, whereas resection of tumors close to major vascular structures is not possible, like liver resection.

Liver cryoablation has been found to be more effective than surgical resection in treating multiple new tumors .

In contrast with other local ablations, such as radiofrequency, which are difficult to reliably destroy tumors greater than 5 cm in diameter, cryoablation would be a promising means for the treatment of this larger form of tumor.

Lastly, the rapid freeze-thaw process could enhance necrosis and help induce an immune response against the surviving tumor cells.

Cryoablation has been considered as a safe modality.Transient intra-ablative hypothermia is the most common side effects. The use of warming blankets and fluid warmers has been proven beneficial. Transient thrombocytopenia and hypoglycemia have been observed. Pleural effusions may occur in tumor mass treated close to the dome of the diaphragm. Cracking of the hepatic capsule is one of the most serious complications of hepatic cryoablation and might occur during the thawing process, and could be controlled with conservative therapies for most of the cases. Cryoshock manifested as varying degrees of acute renal failure, disseminated intravascular coagulation and adult respiratory distress syndrome, was reported. It has been shown that cryoshock occurred in greater than 40 % of the volume of tissue treated, and lesions over 6 cm were associated with a greater risk.However, lesions up to 10 cm in size were treated safely in our series. This complication might be related more to the total duration of cryoablation than to the volume of tumor tissue treated.

2. Radiofrequency ablation

The use of heat to tumors has been part of medical practice from Greek and Egyptian times, when superficial tumors are subjected to cautery. In 1970s and early 1980s,the application of heat from an external source became a focus of care when it was noted that malignant cells were more sensitive to heat than normal parenchyma.
PRINCIPLE
Thermal injury to cells begins at 42?C, with the exposure times to such low-level hyperthermia needed to achieve cell death ranging from 3 to 50 hours depending on the tissue type and conditions. As the temperature increases to above 42?C, there is an exponential decrease in the exposure time necessary for a lethal response.At temperatures above 60?C, intracellular proteins are denatured rapidly, cell membranes are destroyed through dissolution and melting of lipid bilayers, and lastly, cell death is inevitable.

During the application of radiofrequency (RF) energy, a high-frequency alternating current moves from the tip of an electrode into the tissue surrounding that electrode. As the ions within the tissue attempt to follow the change in the direction of the alternating current, their movement results in frictional heating of the tissue. As the temperature within the tissue becomes elevated beyond 60?C, cells begin to die, resulting in a region of necrosis surrounding the electrode.
CLINICAL APPLICATION
RF ablation has shown excellent results in treating liver tumors such as hepatocellular carcinoma, secondary liver cancer. It is especially useful for patients who are not ideal surgical candidates, cannot undergo surgery, have recurrent tumors or don't respond to conventional therapies.
The following types of liver cancers are most likely to be successfully treated with RF ablation:

Tumors 4 cm or smaller,
Three or fewer tumors per patient ,
Patients waiting for a liver transplantation who have a hepatoma.

The most common metastatic disease in the liver treated by RF ablation has been colon cancer. Results with RF ablation are good if the tumors are small and few in number.
RF ablation may also help in patients who are undergoing surgery. For example, RF ablation can be combined with surgery to treat a patient who has several tumors in different locations. RF ablation also can be used to treat tumor recurrence,for instance, in patients who have had surgical resection of a metastatic tumor that recurs.
Lung Cancer that are limited in size (less than 3 cm in diameter)and few in number (one or two) can be treated with RF ablation, if they are separate from vital structures.RF ablation can help lung cancer patients who are not candidates for traditional surgery, due to advanced disease in the lungs, poor cardiac function and/or poor pulmonary function.
The experience with kidney cancer ablation is very encouraging with approximately 95 percent of small tumors showing no evidence of recurrence on follow up imaging exams. Surgery is the treatment of choice for most kidney tumor patients,however, in the following situations, RF ablation might be considered:(1)Patients with one kidney (2)Patients with other medical conditions which might prevent surgery ,(3)Elderly patients in whom surgery or postsurgical recovery would be difficult ,(4)Patients with tumors less than 4 cm in size
Similarly, bone ablation for pain reduction is effective in more than 80 percent of patients treated who have a limited amount of cancer involving the bone. The purpose of the procedure is primarily to treat the pain, rather than to cure the cancer. In Mayo Clinic's experience, 80 percent of patients who have had RF ablation to relieve bone cancer pain reported a significant decrease in pain during the follow-up period, with 44 percent of people reporting total pain relief at some point following treatment.

3. Photodynamic Therapy

It is considered by specialists that photodynamic therapy (PDT), as a scientific,appropriate,noninvasive or microinvasive therapy which developed at the beginning of the 21st century, will open the new epoch in tumor therapy in future, just as penicillin invented in 1930s made death rate of infectious diseases such as pneumonia decrease dramatically.

PRINCIPLE
PDT is a non-thermal light chemical reaction and need oxygen,photosensitive substance(photosensitizer) and laser simultaneously to participate in.Photosensitizer is absorbed by neoplasm tissue and accumulates in the cells for a long time.Photosensitizer is activated with the appropriate wavelength of light and reacts with oxygen to generate reactive single state oxygen and photochemical substance that are toxic to cells leads to apoptosis and necrosis of cancer;PDT can result in local vascular lesion of tumor;PDT can make tumor tissue ischemic necrosis and initiate immune reaction of antitumor.Photosensitizer is exposed to laser light and subsequently reacts with oxygen,and gives rise to single state oxygen and toxic photochemical substance

CLINICAL APPLICATION
The indications of PDT formally approved are esophageal cancer (partically or completely obstructive), early stage esophageal cancer as radical treatment, microinvasive non-small cell lung cancer(unable to be given surgery and radiotherapy),and obstructing non-small cell lung cancer.Now several studies show that the modality is effective for other cancers as well.
? PDT had radical effect for early esophageal cancer with five-year survival rate of 74%-84%,is able to treat undermucosal disseminated and latent cancer and effectively ameliorated obstruction of advanced esophageal carcinoma in more than 80% of patients. For cancer which grows into intracavity and stent has been placed, PDT can eradicate neoplasm in cavity.

For early oral,nosal and nasopharygeal cancer,PDT had effective rates of 75%-100%.
Normal squamous epithelium lining the esophagus is replaced by glandular columanar epithelium, that called Barrett esophagus, which increases the risk of esophageal adenocarcinoma. PDT not only can effectively eradicate Barrett epithelium, but has good result for early adenocarcinoma. For lung cancer PDT induce improvement of air-way obstruction and eradication of early bronchial cancer.It is reported that in patients with stage 1 of bronchial carcinoma,5-year survival rate brought by PDT was as high as 93 percent.In advanced bronchial carcinoma with air-tract obstruction,55% of tumor mass shrunk,49% of improved after PDT. PDT can also induce stopping of hemoptysis induced by various causes.PDT can eradicate cancer for 80 % of early gastric cancer and can improve symptoms of advanced gastric cancer.
PDT is especially indicated to colon-rectal adenocarcinoma，and can improve symptoms,such as tenesmus,pain and bleeding,of 55 percent of patients with unresectable colon-rectal carcinoma. It was reported that PDT can effectively treat the postoperative recurrent cancer of rectum in pelvic cavity, recurrent colonic carcinoma with local metastasis and sarcoma in abdominal cavity.
PDT can effectively eliminate obstruction of bile duct in patients with cholangiocarcinoma in hepatic hilum,treatment of which is very difficult with traditional methods.
PDT, which is performed with inserting light-guiding fiber through endoscopy or percutaneously,can control development of pancreatic carcinoma and Vater’s ampulla cancer.
For pleural and peritoneal mesothelioma,intraoperative application of PDT can eliminate tumor especially for patients with tumor which can’t be totally resected.The 2-year survival rate of 23 % was seen in 37 patients with mesothelioma,and the median survival was 61 months in patients with 1 and 2 stage of disease.
PDT has a special effect to brain tumor,especially to glioma,because cells of brain tumor have high capacity to concentrate photosensitizer.
Bladder cancer in situ can be eradicated by PDT.Seventy-one percent of advanced cases had got improvement after PDT.
PDT can effectively treat various cancer and metastatic cancer of skin and subcutaneous tissues.
PDT is effective for treatment of vaginocarcinoma,cervical cancer in situ,and metastatic vaginocarcinoma.

COMMENT
Compared with other therapies for cancer,PDT is of following advantages:

Relative selectivity and tissue speciality for tumor cells;
Low toxicity,good safety,no immunosuppression and marrow inhibition;
No bad effect on other therapies,complementary to surgery,radiotherapy and chemotherapy;
Short treatment time;
Initiating therapeutic effect within 48-72 hours.

There are limitations of PDT.The light needed to activate most photosensitizers cannot pass through more than about one-third of an inch of tissue. For this reason, PDT is usually used to treat tumors on or just under the skin or on the lining of internal organs or cavities . PDT is also less effective in treating large tumors, because the light cannot pass far into these tumors . PDT is a local treatment and generally cannot be used to treat cancer that has spread cancer.

4. Brachytherapy: Iodine seeds implantation

Seed implantation with iodine-125 or palladium-103 seeds (brachytherapy) is a highly effective treatment for patients with cancer. Seed implantation with iodine-125 seed gives a lower dose rate of radiation than palladium-103.and as iodine-125 works in body longer than palladium-103, it is ideal for treating slow growing tumors such as most prostate cancers.
Before an implantation, an ultrasound volume study to see the size and location of the cancerous mass as well as the surrounding organs. During the pre-plan a predetermination is made of how many seeds a patient will need and exactly where they should be placed based on the size and shape of the cancerous mass. To guide the precise placement of the seeds, an ultrasound probe is placed on cancerous mass so that an image of the mass. Usually 20 to 100 seeds are placed inside needles that are inserted in to the masses The ultrasound probe ensures that the needles are guided with maximum accuracy based on the plan.

INDICATION

Brachytherapy can be used for treatment of many types of cancers:

Prostate cancer
Solid cancer,especially local tumor,such as cancer of oral cavity, tongue cancer, tumor of head-neck
Brain tumor, such as glioma
Postoperative tumor bed, to prevent recurrence

COMMENT
The modality requires no surgical incision, offers patients a shorter recovery time, and has less chance of troubling side effects. For example, for prostate cancer, brachytherapy is an outpatient procedure and most men go home the same day as their treatment. Seed implantation takes only 45 minutes to 1 hour. With brachytherapy, most men can return to their normal activities a few days after treatment.
There is little discomfort after the implantation. These symptoms usually go away in a few days. Some men with prostate cancer may experience discomfort while urinating, or the need to urinate more frequently. These symptoms usually begin 1 to 2 weeks after implantation and gradually decrease over time as the seeds lose their strength. A small percentage of men, particularly those who have had previous prostate surgery, may experience incontinence. Impotence may also occur in some men, particularly those over the age of 70. However, the rates of impotence and incontinence are lower with iodine-125 seeds than with other treatments.
5. Dendritic cell vaccine
Dendritic cells (DC) are the professional antigen-presenting cells(APC), and can be found in most areas of the body. They circulate in peripheral blood, and are present as Langerhans cells in the epidermis.
PRINCIPLE
Dendritic cells are potentially good candidates for immune-based therapies for a variety of reasons. In particular, the following aspects are important---

Their ability to migrate through tissues and infiltrate into tumours, where they encounter tumor-associated antigens(TAAgs) which they capture, digest, and re-express for effective induction of a CMI response;
Their capacity to activate native T cells in regional lymph nodes and their differentiation into CTLs, specifically able to interact with cancer cells and lead to tumour cell damage and death;and
Their role as APCs and capacity to process and present a spectrum of different Ags simultaneously that allows for the induction of a broad repertoire of anti-tumour immune responses to occur.

Biotherapy with tumor lysate-pulsed dendritic cells elicits antigen-specific cytotoxic T cells. Presentation of tumor lysate-pulsed dendritic cell(DC) can induce a T cell-mediated anti-tumour immune response. DC which is derived from peripheral blood monocyte is induced by rhGM-CSF and rhIL-4,forming iDCs,and then the tumor cell antigens are loaded to iDCs with rhTNF-α, rhIL-1β. After iDC changed to matured DC(mDC), mDC combined with rhIL-2 and rhIL-6 to active tumor specific cytotoxicty T Lymphocytes(CTLs). Then, both tumer antigen-pulsed dendritic cells are infused to patient through vein route. A cycle needs about 10 days.

CLINICAL APPLICATION
There were a lot of experience with dendritic cell vaccines in the past years. First, dendritic cell-based immunizations are feasible and safe. Clinically significant adverse events are exceedingly rare. Second, low levels of antigen-specific immune responses can be induced in some patients . Third, clinical responses, including complete responses, can be evoked in a minority of patients and these responses are more common in studies targeting melanoma. Fourth, no one strategy appears to be significantly more effective.
In certain types of cancer, such as the skin cancer malignant melanoma, it is known that patients can mount an immune response to the developing tumour. However, in many cases this response ultimately fails. Beefed-up dendritic cells help to maintain this response in these patients.
The patients with breast cancer,non-Hodgkin lymphoma,renal cell cancer,glioma,parathyroid cancer, who have not responded to conventional treatments and have metastatic skin lesions, can response to DC therapy.
Dendritic cell therapy alone may also prove useful for patients at high risk of recurrence after a primary tumour has been removed by surgery, or for healthy people at risk of developing familial types of cancer. Promising preliminary results have been received from clinical trials for hepatocellular carcinoma,lung cancer,colonrectal cancer, nasopharygeal cancer, esophageal cancer and thyroid cancer as well.

TRADITIONAL CHINESE MEDICINE（Research results in China mainly）
Traditional Chinese medicine (TCM) has been used to treat various diseases in China for thousands of years. For nearly 40 years, cancer treatment with TCM has been investigated systematically in China.
At Present, there are following two main therapeutic methods for treating cancer in traditional medicine. One is to find some Chinese herbs that aim at killing cancer cells. The other is referred to as dialectic therapy(differentiation of symptoms and signs therapy), which means determination of the treatment principles based on patients different symptoms and signs according to the theory of TCM.
The clinical effects of dialectic therapy may be attributed to :

Relieving symptoms, such as pain,cough,abdomen distention, fatigue, dyspepsia, and weight loss. After treatment with dialectic therapy the majority of the above symptoms might subside. Some times, in spite of progressive tumor growth, the patients’ symptoms might be alleviated for about 1 or 3 months.
Improving survival quality. After treatment, the patients with cancer may put on weight, have good appetite and spirit,and can take care of themselves
Improving organ function.
Obtaining a long survival. It was reported that in a group of 27 pathologically proven hepatocellular carcinoma patients, the 1-year survival rate was 44.4%and 5-year survival rate was 15.5% with TCM alone.

Recently laboratory work on the effects of traditional Chinese medicine in the treatment of liver cancer has been carried out. It consists of followings:

Direct antitumor effects of Chinese herbs and extracting effective chemical constituents
Up to now more than 2000 Chinese herbs and hundreds of complex prescriptions have been screened in China. Among them 190 Chinese herbs and 30 complex prescriptions have been proved to be effective against tumor to some extent. Substances such as leurocristine, camptothecine, maytansine, terpenes, flavonoides, triptolide, and ensatanine A are available as antitumor agents(Li and Huang 1984).

Maytansine and maytanprine have active antitumor effects which can prolong the survival of mice bearing hepatoma ascitis cells (HAC). Matrine, dehydromatrine, and oxynatrube extracted from Sophora flavescens;harringtonine extracted from Ketelecria davidiana; and β-elemene and five terpenes(A,B,C,D,E) extracted from Rhizoma zedoaria and Rabdosia rubescens respectively are all antitumor elements(Huang and Jeng 1984). In 1972, our scientists obtained a series of active antitumor agents such as camptothecine, 10-hydroxycamptothecine, and 10-methoxy camptothecin, and on this basis they synthesized 11-methoxycamptothecin and 10-hydroxycamptothecin, the latter being more effective against tumor and having less toxicity to host. The value of these agents has been confirmed by long-term survival rate in liver cancer and stomach carcinoma
The main mechanisms of the antitumor herbs are suppression of the biosynthesis of DNA, RNA, and proteins, and interference with the proliferation of tumor cells. In experimental study it has been demonstrated that harringtonine can disturb the polymerism of deoxynucleotide triphosphate into DNA, but there is no effect on reduction of ribonucleoside triphosphate (Xu and Du 1981). Ensatanine can interfere with proliferation of nuclei. 10-Hydroxycamptothecine can control the stop apparatus of cell division through the cyclic AMP system, and act on the specific locus of the DNA chain to suppress cell proliferation (Yang et al. 1981).β-Elemene and terpenes extracted from Rhizoma zedoaride can effectively kill liver cancer cells by suppressing DNA and RNA synthesis, while it has less effect on granulocytes and myelocytes, so it has little toxicity to bone marrow (Fu et al. 1984). It has been demonstrated in laboratory studies that the five terpenes in Rabdosia rubescens can kill liver cancer cells in rats, which is also effective in clinical investigation. By means of available techniques such as the 3H-TdR-Labeled, colchicines-blocking test and continuously labeled 3H-TdR, it has been reported(Zhang 1982) that five terpenes can block cells at stage S, interfere with stage G2 cells entering into stage M, and kill cells at stage M or G1.

Recently some extracting effective chemical constituents from Chinese medicine has been approved for treatment of cancers including hemotologic malignancies.For example--

Arsenic trioxide (As2O3) :Arsenic trioxide (As2O3) has been shown to be effective for treatment of patients with refractory or relapsed acute promyelocytic leukemia and a variety of other malignant hematopoetic disorders. Tan et al showed that Arsenic trioxide inhibits growth of experimental hepatocellular carcinoma in rats induced by 2-acetamidofluorene, but As2O3 has no obvious effect on the normal hepatic cells. It’s mechanisms may be the following effects:

Inhibition of proliferation of liver cancer cell:Oketani et al shows that the effect of this agent on proliferation of human hepatoma-derived cell lines: reducing proliferation time- and dose-dependently cells; inducing apoptosis in hepatoma-derived cells. Sensitivity of hepatoma-derived cells to As2O3was inversely related to their intracellular glutathione (GSH) and intensity of GSH synthesis. These results indicate that As2O3 may have therapeutic potential for treatment of hepatocellular carcinoma. Su et al showed that arsenic trioxide may inhibit the proliferation of hepatoma cells in a time-and concentration-dependent manner, and suppress the expression of telomerase and induce apoptosis of human hepatoma cells.

Anti-vascularization Hua et al showed that As2O3 injection can inhibit the tumor neovascularization by supressing the growth of vascular endothelial cell, down-regulating the expression of VEGF,damaging the primitive mesenchymal cells and inhibiting neovascular fromation.
Apoptosis-inducing effect Liu et al showed that As2O3has significant apoptosis-inducing effect on large intestinal carcinoma cells, which is regulated by several genes.

Seminal oil emulsion of Brucea javanica:Ma et al showed that the proliferation of hepatocellular carcinoma cell line SMMC-7721 could be remarkably inhibited by seminal oil emulsion of Brucea javanica in a time- and concentrationdependent manner. Morphological and biochemical changes characteristic of apoptosis were observed through electron microscope and agarose gel electrophoresis. Cell cycle was arrested at G0/G1 phase. The expression of p53 and Bcl-2 was downregulated after exposure to the drug, with a positive correlation between them,suggest that Seminal oil emulsion of Brucea javanica can significantly inhibit the proliferation of human hepatocellular carcinoma cell through inducing apoptosis and arresting cell cycle at G0/G1 phase, and its underlying mechanism is related to the down-regulating mutant type p53 as well as Bcl-2, with p53 pathway playing a leading role.

Weikangning胃复康(WKN):Min et al studied effect of traditional Chinese medicine胃复康Weikangning (WKN) on the expression of VEGF and itsreceptors Flt and KDR in gastric carcinoma cells. They used different dosage of WKN on rats to prepare serum containing WKN.The gastric carcinoma cells were cultured in the RPMI1640 media with serum containing WKN for 48 hours. The expression of VEGF, Flt-1 and KDR was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in gastriccancer cell lines respectively. Results showed all gastric cancer cell lines analyzed expressed. VEGF Flt-1 and KDR. But the expression of fVEGF, Flt-1 in cells cultured in serum containing WKN decreased in a dose-dependent manner as compared with control. Hence, WKN can inhibit VEGF and its receptors KDR and Flt-1their expression in gastric carcinoma cells.

Stimulating the body’s immunologic defense
Many data reported that some Chinese medicines can interfere with progressive tumor growth, but do not dill tumor cells directly. For example, the suppression rate of lentinan against sarcoma S180 is more than 95%, of methyl-ester-Poria polysaccharide 90%, and of Polyporus umbellatus polysaccharide 50%-70%. These medicines are thought to enhance the natural defense of the host, which may result in a favorable outcome. Preliminary experimental trials with the herbs indicated that the medicines increased the weight of the thymus and spleen, activated immunocompetent cells such as macrophages, monocytes, and T-lymphocytes, and therefore produced a series of immunomodultion agents including interferone (Wandg et al. 1982).The following Chinese herbs have the same effect: Radix astragalisen hedysari, Radix adenophororas, Radix ophiopogonis, Radix rehmannia, Rhizoma atractylodis macrocephala, Radix ginseng, Radix codonopsis pilosula, Furctus ligustri lucidi, Radix polygoni multiflori, and Fructus lycii.

Improving the body’s physical and pathologic Conditions
Preserving the subnormal metabolism. Many Chinese herbs “invigorating the spleen and regulating vital energy” (Jian Pi Li Qi) can stimulate protein metabolism and glycometabolism. Si Jun Zi decoction can increase the amount of glycogen in the liver. The level of serum albumin can be elevated by feeding Radix astragalisen hedysari for a week in toxic mice caused by carbon tetrachloride. Radix codonopsis pilosula, Rhizoma atractylodis macrocephala, and Poria can protect mice liver from CCl4 toxication, manifestating a lower level of serum alanine transaminase (ALT) and alpha-fetoprotein in the condition of injured liver.

Preserving the marrow function. The extract F4 from Radix ginseng not only stimulates the DNA synthesis in the bone marrow but also affects the metabolism of fatty acid, steroid, phosphatide, and protein. Ginsenosides introduce nondividing cells into the cell cycle. Sheng Mei powder stimulates the proliferation of stem cells through humoral factors.

Keeping the body homeostatic. Radix astragalisen hedysari can maintain a balanced system of control factor in plasma or kidney, regulating RNA metabolism and thereby preventing mercury-intoxicating kidney. The mixture of “invigorating the spleen and regulating vital energy” can regulate the activity of cytochrome P450 in carbon tetrachloride toxiic hepatitis in rats (Shen et al. 1985).
The data from the above studies provided a firm theoretical basis for the use of Chinese medicine in treatment of cancer in order to prevent the side effects of chemotherapy and radiotherapy.

Increasing the effectiveness of chemotherapy and radiotherapy
Many tumors contain a population of cells which are resistant to radiotherapy and chemotherapy. A group of Chinese herbs that clear away “heat and toxic” materials have been demonstrated to increase the sensitivity of tumor cells to chemotherapy, such as Radix sophorae subprostrata, Spica prunella, and Hedyotis diffusa. The herbs which promote blood circulation and resolve “stasis”, such as Radix salviae miltiorrizae, appear to be beneficial to therapy with camptothecin. Some herbs such as Radix rehmannia and Radix scrophulariae, which invigorate Yin, increase toxicity of cytoxan to tumor cells. Numerous in vivo animal studies have revealed that Poria polysaccharide combined with cytoxan, fluorouracil, mitomycin, or vincristine(VCR) leads to successful antitumor chemotherapy.

Ensatanine A as a chemotherapeutic agent, has a radiosensitizing effect, and its radiosensitizing index for hypoxic cells is 1.34. As a consequence of these experimental reports, the radiosensitizers are currently being evaluated in clinical studies. The mechanisms of the radiosensitizing effect are complex, and may be helpful in improving the blood supply of the tumor site and preventing surrounding normal tissues from trauma caused by radiation.

COMBINATION THERAPY

For advanced cancer the best therapy is combination of different modalities.We have made trials.For example—

Combination of cryoablation with alcohol injection for liver cancer
For advanced hepatocellular carcinoma,we used percutaneous cryoablation combined with percutaneous alcohol injection. A total of 105 masses in 65 HCC patients was underwent percutaneous hepatic cryoablation. The cryoablation was performed with the Cryocare system(Endocare,Irvine,CA,USA) by using argon gas as a cryogen.Two freeze-thaw cycles were performed,each reaching a temperature of –180? C at the tip of the probe.PEI was used in was given in 36 patients with tumor mass larger than 6 cm in diameter,was given since 1-2 weeks after cryoablation and then once per week for up to 4 to 6 sessions. During mean follow-up duration of 16 months with a range of 5 to 21 months,33 patients (50.8 %) are currently free of tumor,21 patients (32.3 %) are alive with tumor recurrence, of whom only 3 developed a cryosite recurrence. Among 41 patients who were given followed up more than one year,there was a total of 32(78.0%).Eight patients (12.3 %) have died with their disease recurrence. Among 43 patients who had a CT scan available for review,38 (88.4%) had a shrinkage of tumor mass.Among 22 patients received biopsies of cryoablated tumor mass,all biopsies, except one, showed only dead or scar tissue. 91.3% of patients who had an increased serum AFP precryoablatively, had a decrease of AFP to normal or nearly normal levels during postoperative 3-6 months.

During cryoablation, freezing would occur in three main areas:(1) The center of iceball near the cryoprobe, where freezing would be rapid and the temperature would be lowest.(2) The middle of the iceball, where the tissue experienced intermediate cooling rate.(3) The periphery of the iceball, where slow rates of cooling would occur[18].The cytotoxic effect from rapid cooling was the greatest in the center of the iceball, while cells at the periphery of the iceball might survive, particularly if the tumor abutted a large intrahepatic blood vessel that abrogated the effects of tissue cooling. The surviving tumor cells would result in recurrence of the disease. PEI has been used extensively for treatment of HCC. Ethanol could diffuse into the tumor cells and cause nonselective protein denaturation and cellular dehydration, leading to coagulated necrosis. Subsequent fibrosis and small vessel thrombosis would also contribute to cellular death. Therefore, after cryoablation which could destroy the majority of tumors , PEI used at periphery of tumor could destroy residue tumor tissues. It is obvious that cryoablation in combination with PEI had a complementary effects on preventing recurrence.

Transarterial chemoembolization(TACE) with cryoablation for liver cancer
Three hundred and sixty patients with PLC were received the therapy.Intrahepatic tumor masses were larger than 5 cm in size. The tumors of all patients were considered to be unresectable. TACE was completed according to routine method. 2-3 weeks later,the cryoablation was performed.One month after cryoablation,the TACE of one or two times may be further performed if necessary. Results showed that among the follow-up period of median 21 months(6-36 months),ultrasound and /or CT showed that a complete response(CR) of 8.3%,partial response (PR) 63.3%. AFP was significantly decreased and decreased into normal range,in 86.9% and 62.0%, respectively. Survival rate of 6 months was 90.6%,12months 70.0%,24 months 52.1%, and 36 months 41.1%.The data show that sequential treatment of TACE-percutaneous cryoablation offers a safe and effective treatment options and may result in a shrinkage or eradication of tumor mass and increase of survival for patients with unresectable HCC.
Combination of photodynamic therapy with cryoablation for lung cancer
Forty-one patients with obstructive non-small cell lung carcinoma,whose tumors were considered nonresectable because of local aggression of tumor (stage Ⅲb on TNM)or poor lung function of patients(severe obstructive lung disease),were given the combination therapy.At first, photodynamic therapy was performed. Then,percutaneous cryoablation with argon-helium system under guidance of B-mode sonography or CT was given. Results showed that 90.2 %patients of had some improvement of subjective symptoms,significant decrease of symptom score, especially marked relief of dyspnoea.Bronchoscopy showed that endobronchial tumor was ablated on different degrees in all patients, with complete resolution in 41.5 % of patients.CT showed that lung tumor had CR of 34.1% and PR of 41.4%.According to the radiographic evidence,collapse of lung resolved completely in 29.6% of patients with previous collapse, and diminished in 70.4% of patients.The 6- and 12-month survival rate were 71% and 44% respectively. The data suggests that photodynamic therapy and percutaneous cryoablation with argon-helium system can eliminate endo- and extra-bronchial tumor masses,respectively, and the combination is complementary to each other,therefore,raise the therapeutic efficacy for unresectable obstructive non-small cell lung carcinoma.

Combination of photodynamic therapy with transarterial intervention therapy for nasopharygeal cancer
Twenty two patients with nasopharygeal cancer received combination treatment consisted of photodynamic therapy and transarterial intervention therapy(regional chemotherapy).Male 15 cases and female 7 cases.Average age was 46 years old with range of 26 to 65.Disease stage based on AJCC stage: IIA in 3 cases, IIB 11 cases, III 6 cases,and IVA 2 cases.15 patients had received systemic chemotherapy and radiotherapy before.Results: CR 2 cases,PR 13 ,NC (no change) 4 and PD (progressive disease) 3. The 12- and 24-month survival rate were 100% and 74% respectively.

Combination of iodine-125 seed placement,cryoablation with transarterial intervention for recurrent breast cancer
Thirty one patients with recurrent breast cancer, who had been given chemotherapy and radiotherapy before,received combination therapy:①use of cryoablation to decrease or eradicate cancer mass;②placement of iodine-125 seeds into residual cancer mass;③regional chemotherapy through transarterial intervention route.Results:CR 8 cases,PR 18,NC 3 and PD 2.Twenty one cases are alive up to now.One-year survival rate was 84%,2-year 75% and 3-year 68%.There was one patient who had metastasis of chest spine on C12 level ,which injured spinal cord and induced paralysis of lower limbs,and received placement of iodine-125 seeds and regional chemotherapy.Two months later,her spine metastasis disappeared and movement of lower limbs totally recovered.

Combination of modern therapies with traditional Chinese medicine
For most of hospitalized patients with cancer,we give modern therapies and traditional Chinese medicine(TCM).Combination of both modalities is usually used for (1)prevention of recurrence of cancer,(2)as a complementary therapy which increase therapeutic efficacy,(3)control of pain and other symptoms,and (4)increase of patient’s life quality.

Wang et al reported that fifty six patients with gastric cancer stage 3 or 4 randomly received chemotherapy with or without immunotherapy and TCM (172 and 158 cases repectively),5-year survival rates were 30.4% and 12%, respectively.

Xun et al reported that 223 patients with esophageal cancer received combination of chemotherapy with TCM, 1-and 5-year survival rate was 42% and 7.1%, respectively.

Qiu et al reported patients with nasopharyngeal cancer randomly receved combination of radiotherapy with Chinese herb(flower power花粉) and radiotherapy alone,2-year survival rates were 81.8% and 62.5%,2-year tumor-free survival rates were 63.6% and 31.3%.

References

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