I. Overview
Photodynamic therapy (PDT) has a history of more than 4000 years (ancient Egyptian era) [1]. 1895 was the first time that Finsen and Raab et al. wrote about photodynamics. 1960 Lipson prepared hematoporphyrin derivatives (HPD) and one year later he reported 15 cases of endobronchial tumors that fluoresced after injection of hematoporphyrin derivatives (HPD). In the late 1970s, PDT gradually became a new technique for the treatment of tumors and was approved by many countries such as the United States, the United Kingdom, France, Germany, and Japan.
In 1980, Hayata (Hayata Yoshihiro) first reported the application of PDT through fiberoptic endoscopy to treat 13 cases of endobronchial tumors. 1984, Roswell Park Cancer Institute isolated the highly effective component Photofrin from HPD, which became the basic photosensitizer of PDT. 1998, the US FDA approved Photofrin? for the treatment of early stage Bronchial cancer and obstructive bronchopulmonary cancer treatment.
II. Mechanism of photodynamic therapy for tumors [1]
1.Photosensitization response
The photophysical and photochemical properties of different photosensitizers vary greatly, but the pathways to produce photosensitizing effects are similar. After the body receives photosensitizer for a certain period of time, the photosensitizer can be more retained in the tumor tissue. At this time, when the tumor site is irradiated with light of specific wavelength, the photosensitizer, after absorbing the activated light of suitable wavelength, changes from the ground state to the activated monocline state, and then reacts with oxygen to produce highly reactive monocline molecules (002), which reacts with molecular oxygen to produce excited reactive monocline oxygen, and then reacts with the neighboring The latter reacts with molecular oxygen to produce excited reactive singlet oxygen, and then reacts with neighboring molecules (such as amino acids, fatty acids or nucleic acids) to produce toxic photochemical products, causing cytotoxicity and local microvascular damage.
2.The in vivo mechanism of PDT tumor killing
(1) The effect of PDT on tumor cells: PDT has a direct killing effect on tumor cells.
(2) Effect of PDT on microvasculature: The photosensitive reaction of PDT can cause microvascular destruction, activate platelets and inflammatory cells, lead to the release of inflammatory factors, cause vasoconstriction, blood cell retention and agglutination, blood flow stagnation causing tissue edema, ischemia and hypoxia, thus killing tumors.
(3) The effect of PDT on interstitium: interstitium is the “tumor bed” for tumor cell growth, which plays an important role in material diffusion, transporting nucleus neovascularization, and the content of photosensitizer in interstitium is high.
(4) PDT can still secondary to anti-tumor immune response.
III. Equipment
1.Photosensitizer
Photosensitizers are porphyrin-like molecules that can absorb and re-release special wavelengths and have a tetrapyrrole-based structure. The mechanism of selective uptake of photosensitizers by tumors is not well understood and may include.
(1) Porphyrins can passively diffuse into cells, and the diffusion efficiency is related to the extracellular pH, the lower the pH the more diffusion. Tumor tissue has accelerated metabolism, so that its extracellular pH is lower than that of normal tissue, and more porphyrins enter tumor cells.
(2) HPD and Photofrin bind to serum albumin and lipoprotein, especially low-density lipoprotein (LDL). Since tumor cells have more LDL receptors than normal cells, photosensitizers can enter tumor cells more often through LDL receptor mediation. The tumor tissues take up the photosensitizer predominantly and stay in it for a longer period of time. For example, the ratio of tumor to normal tissue concentration of photosensitizers in brain tumors is 12:1.
Four photosensitizing drugs have been approved by the FDA, namely Photofrin ? (generic name porfimer sodium), Visudyne (generic name verteporfin, or chemical structure abbreviated BPD-MA), 5-aminolaevulinic acid (ALA), and Foscan.
The first generation photosensitizers were HPD, dihaematoporphyrin ether (DHE), or porfimer sodinm (Photofrin). photofrin was the first photosensitizer approved for use, and Photofrin? was marketed in 1993 and was first used in Canada for the treatment of early-stage It has been approved by governmental drug regulatory authorities in more than a dozen countries, including the United States, Canada, France, the Netherlands, Germany, the United Kingdom, Japan, and Korea, for the routine treatment of patients with certain types of tumors in esophageal, lung, bladder, cervical, and skin cancers, respectively.
Second-generation photosensitizers include 5-aminoketovaleric acid (5-ALA), meso tetrahydroxyphenyl chlorin (mTHPC), tin etiopurpurin (SnEtz), methylene blue and toluidine blue, zinc phthalocyanines and aluminium phthalocyanines, benzoporphyrin derivatives, and lutelium texaphyrins (Lu-Tex), mono-l-aspartyl chlorine e6 (talaporfin sodium, NPe6). The second-generation photosensitizers partially overcome the shortcomings of the first-generation photosensitizers by showing a shorter photosensitization period, longer wavelengths of the acting light waves, thus increasing the depth of action and producing more monomorphic oxygen, which is more selective for tumors.
5-ALA is a precursor of heme, which is not a photosensitizer itself and has no photosensitizing activity. It can be taken orally and converted into photo-reactive protoporphyrin IX derivative (PPⅨ) in vivo by ALA dehydratase and a series of enzymatic effects. The uptake of ALA by metabolically active tumor cells increases significantly, producing a large amount of PPⅨ, which accumulates in the cells and undergoes photodynamic reaction after laser irradiation to kill tumor cells. Because ALA itself is a component of normal cells, the toxicity is very low, but the penetrating power only reaches 0.3~0.5cm, so it is mainly used for the treatment of non-tumor diseases (such as age-related fundus macular degeneration, photochemical keratosis) and superficial tumors. the half-life of ALA is very short, generally the concentration of PPⅨ reaches the peak at 3~6h, and after 24h the organs have rarely shown the fluorescence of PPⅨ.
Domestic cancer photophorin, hematoporphyrin monomethyl ether, chlorophyll photosensitizer CPD-4, etc., also show good effect in PDT treatment.
The third-generation photosensitizer Foscan has been approved for clinical use by the U.S. FDA in 2002 and approved by European CE. Its penetration power reaches about 2cm with a wavelength of 652nm.
Photosensitizers are different from anticancer chemotherapy drugs. After entering the human body, photosensitized drugs quickly form different concentration distributions in different tissues, and then decline at different rates, and are largely excreted after several days. Human tissues that have ingested the drug will not trigger a photodynamic response and produce cytotoxicity if they are not irradiated by light. Even if irradiated with light, no major cellular damage occurs as long as the wavelength of light, the amount of irradiation, or the concentration of the drug in the tissue does not meet certain requirements. It must be used in combination with a dedicated photodynamic laser machine to produce a therapeutic effect on the patient. The principle of action of general chemotherapy drugs is completely different, they enter the body without additional conditions and special equipment to have cytotoxic, not only can kill cancer cells, many normal organs and cells can also cause varying degrees of damage, is a systemic toxic effects, such as the inhibition of the hematopoietic system and immune system, often bring great pain to patients.
2.Illumination light
Irradiation light is often used visible red light. Currently commonly used 630nm or 650nm laser. It is found that the most obvious necrotic effect is caused by red light in tumors with a depth of more than 1.2±0.5mm, green light is more effective in superficial tumors, while violet light is most effective only in lesions with a depth of less than 0.2±0.1mm. The photosensitive killing effect of violet light is 12 times more than that of red light.
3.Photodynamic laser therapy instrument
From the early 1980s to the late 1990s, major PDT clinical research centers around the world have been using argon laser-pumped dye laser systems as a supporting light source for PDT. However, this laser system requires three-phase electricity and water cooling, large size, heavy mass, high power consumption, inconvenient use, unfavorable maintenance, and encountered great difficulties in the promotion of hospitals, and these lasers have been eliminated at present. In recent years, with the birth of high-power semiconductor lasers, PDT finally has a practical supporting light source. Semiconductor lasers are small in size, high in efficiency, stable in performance and simple in operation, but more expensive.
At present, the main photodynamic lasers used in clinical practice are semiconductor lasers and high-power helium-neon laser tumor treatment devices.
Semiconductor lasers are available in two models with output wavelengths of 630 nm and 652 nm. semiconductor lasers are manufactured from gallium arsenide semiconductor material and mounted on a protected heat sink assembly with wrinkled slots and high energy fan cooling without water cooling, ensuring low maintenance and reliable laser operation with the laser operating in continuous mode.
In recent years, a 1000mW high power helium-neon laser tumor treatment device (630nm wavelength) has been successfully developed in China and has been listed as a key new product by the Ministry of Science and Technology of the People’s Republic of China, and has achieved very good clinical results. Ltd.
Ltd. has been widely used in China with stable performance.
Fourth, the treatment method
1.Drug delivery method
PDT is done in two steps. First, the patient is given photosensitizer (allergy test is required before drug administration if necessary), and is protected from light after drug administration. Then, laser irradiation is applied to the lesion area. The commonly used photosensitizer in clinical practice is Photofrin? and patients usually need to wait 40~50h after injection before laser irradiation. At this time, the concentration of photosensitizer in the lesion tissue remains at a high level, while the concentration of photosensitizer in the surrounding normal tissue has dropped to a low level. Choose this time to irradiate light, not only can effectively kill the lesion tissue, but also can reduce the damage to the surrounding normal tissue, and strive to obtain the best targeted killing effect.
2.Irradiation dose
The irradiation power density is generally 100~250mW/cm2 and energy density is 100~500J/cm2, depending on the type, size and location of the tumor.
Estimation of irradiation depth: It is reported that the irradiation dose of bronchial cancer is 495J/cm2 (330 mW, 30 min), and after irradiation and removal of tumor, it is found that there is obvious degenerative change in the depth of tumor tissue within 3 cm, but there is no such change in normal tissue. It was concluded that the killing depth of 630 nm red light on tumor was 3 cm, and the surface dirt of tumor should be removed before irradiation to avoid affecting the efficacy.
Table 1 Calculation method of laser energy [1]
Tumor thickness (cm) Illumination power density (mW/cm2) Energy density (J/cm2)
<0.5 200 400
0.5~1.0 300 480
1.0~1.4 400 720
>1.5 Inter-tissue insertion irradiation
Photodynamic therapy is a local treatment method, and the killing effect on tumor is largely determined by the adequacy of the light dose in the lesion area. Since the light will be attenuated by the absorption and scattering of tissues after entering the tissues, the killing depth and scope of one irradiation is limited no matter what kind of light is used, and should be repeated if necessary, with the interval depending on the size and scope of the tumor, generally about 2 months.
3.Patients’ preoperative preparation and precautions.
(1) ward requirements: the doors and windows of the ward must be covered with black shading cloth, and low-power milky white lighting or table lamps should be used; (2) patients need to wear sunglasses and stay in the dark room in time after the injection of photosensitizer, and pay attention to the observation of the changes of the disease.
(3) PDT should be done 40~50h after photosensitizer injection and repeated the next day if necessary.
(4) Patients’ local mucosal edema should be observed within three days after PDT, especially for patients with bronchial cancer and laryngeal cancer after PDT, to prevent severe edema of the larynx or bronchial mucosa leading to play obstruction. Prophylactic use of hormones for two days if necessary.
(5) Pay attention to observe the tumor necrosis in patients with bronchopulmonary cancer from day 2 to 4 weeks after PDT to prevent large pieces of tumor necrosis from falling off and causing airway obstruction or trauma bleeding. Remove the necrotic material with tracheoscope if necessary to keep the airway unobstructed. Patients with esophageal cancer should also pay attention to the rare complications such as perforation and bleeding; pay attention to the exposed part of the patient’s skin at any time within 1 month, if photoallergic dermatitis appears, timely anti-allergic symptomatic treatment should be given; after 1 month, let a small part of the skin be exposed to sunlight first and confirm that there are no allergic symptoms before going out.
4.Staff precautions
(1) The level 4 laser produced by the photodynamic instrument is dangerous to the eyes. Eye or skin exposure to the beam should be avoided, and all areas where the laser is used must be given protective measures. Especially when the laser system is working, all people must wear eye protection. Do not look at the beam being positioned or observe the laser rays directly through the optical equipment. Avoid placing reflective materials such as metal and glass in the room. Care must be taken to prevent persons not wearing protective eyewear from entering the treatment room by placing a visible sign on the operating room door.
Protective eyewear should be used exclusively for the semiconductor laser wavelength range 630 nm with an optical density greater than 4. Other sunglasses are inappropriate for eye protection. Qualified glasses can be obtained from agents.
(2) Disinfection of the protective sleeve should be ensured to avoid fiber contamination. Disinfection protective cover made of PTFE material, can be used repeatedly and disinfected with ordinary disinfection solution, the recommended disinfection method is 121 ℃ high temperature and high pressure steam disinfection. Fiber can not be disinfected at high temperature and high pressure, but can be disinfected with ordinary disinfection solution.
(3) Do not use anesthetic gases that are flammable or explosive and may be ignited by the laser. Avoid using other flammable or volatile gas substances in the equipment operation site.
(4) Users should read through and thoroughly familiarize themselves with the machine’s operation manual before operating the laser equipment.
5. Advantages of photodynamic therapy.
Compared with surgery, chemotherapy, radiotherapy and other conventional treatments, photodynamic therapy has the following important advantages.
(1) Targeted accuracy: The main target of PDT is the lesion tissue in the illuminated area, and the damage to the normal tissues around the lesion is slight, and this selective killing effect is difficult to achieve with many other treatments.
(2) Less invasive: With the help of optical fiber, endoscope and other interventional techniques, the laser can be guided deep into the body for treatment, avoiding the trauma and pain caused by open-chest and open-abdomen surgery. The treatment time is short, and the effect can occur in 48~72h.
(3) Good applicability: It has relative selectivity and tissue specificity for tumor cells, but it is effective for different cell types of cancer tissues, so it has a wide range of applicability.
(4) Repeated treatment: Cancer cells are not resistant to photosensitive drugs, and patients will not have increased toxic reactions due to multiple PDT, so it can be used for multiple courses without drug tolerance.
(5) Radical or palliative treatment: For early superficial tumors, PDT can completely eliminate the tumor and achieve the effect of radical treatment. For patients with advanced tumors or those who cannot receive surgery due to advanced age, heart, lung, liver, kidney insufficiency or hemophilia, PDT is a palliative treatment that can effectively relieve pain, improve quality of life and prolong life.
(6) Synergistic treatment: PDT can produce synergistic effects with other treatments. PDT is not excluded from radiotherapy, chemotherapy or surgery, and it can be used for patients who fail in radiotherapy, chemotherapy or surgery.
(7) Eliminate hidden cancer foci: clinically, some tumors, such as bladder metastatic cell carcinoma, may have scattered microscopic cancer nests invisible to the naked eye outside the main lesion, and conventional treatment can only remove the main lesion, but can do nothing about hidden cancer nests.
(8) Protection of appearance and important organ functions: For skin cancer, oral cancer, penile cancer, cervical cancer and retinoblastoma of the face, the application of PDT can effectively kill cancer tissues while minimizing damage to the epithelial structure and collagen scaffold of the organ of origin, so that the appearance is less affected and the appearance of the organ is kept intact and normal physiological functions are maintained after the wound heals.
(9) Low toxicity: low toxicity, safe, does not cause immunosuppression and bone marrow suppression. The photodynamic drug that enters the tissue
(9) Low toxicity: low toxicity, safe, will not cause immunosuppression and bone marrow suppression. The part of human body that is not irradiated by light does not produce such reaction, and other parts of organs and tissues are not damaged, and the hematopoietic function is not affected, so the toxic side effects of photodynamic therapy are very low, and patients recover quickly after treatment and shorten the hospitalization time.
6.Efficacy judgment
In June 1984, the National Conference on Laser Hematoporphyrin formulated the “PDT efficacy criteria”.
(1) Recent efficacy criteria
Complete remission (CR): The visible tumor disappears completely for 1 month.
Significant remission (SR): The product of the maximum diameter of the tumor and its vertical diameter or tumor height is reduced by more than 50%, and lasts for one month.
Minor remission (MR): The product of the maximum diameter of the tumor and its vertical diameter or the height of the tumor is less than 50% and lasts for one month.
No effect (no remission, NR): The tumor does not shrink or increase in size.
(2) Median stable stage: the product of two diameters of the lesion increased by 25% from the beginning of the first treatment.
(3) Median post-treatment survival: the time from the start of the first treatment to death or the last follow-up.
V. Clinical application
1.Nasopharyngeal cancer
As of 2011, 1500 patients with head and neck tumors have received PDT [2]. Nasopharyngeal cancer is a common malignant tumor of the head and neck, and radiotherapy is currently the preferred method. Lorenz reported [3] that in 35 patients with recurrent or secondary head and neck tumors that were not suitable for other treatments, the local control rate after PDT was 60% without serious complications. The maximum thickness of the tumor in these patients was 10 mm.
Sun Zhenquan reported [4] 191 cases of nasopharyngeal carcinoma, of which 120 cases were recurrence and 71 cases were residual after radiotherapy. the recent efficiency of PDT was 89.5%; among the 130 cases with a full 5-year follow-up, the 3-year and 5-year survival rates were 44.6% and 25.4%, respectively. It significantly improved the quality of survival and prolonged the survival period of patients, and a few patients even obtained clinical cure.
2.Laryngeal cancer
American scholar Rigual[5] proposed that the inclusion indications for PDT for oral and laryngeal cancers are:
(1) Adults aged 18 years or older, and women must be non-pregnant or definitely able to use contraception, sterile or post-menopausal during the treatment period.
(2) Moderate to severe anomalous hyperplasia or squamous carcinoma in situ (CIS) of the larynx;
(3) Stage I (T1N0) squamous carcinoma of the larynx with a lesion depth of no more than 3 mm;
(4) Biopsy to confirm the diagnosis;
(5) ECOG (Eastern Cooperative Oncology Group) score of 0 to 2.
(6) Patients had to sign an informed consent form.
They had 30 patients enrolled, 26 of whom were evaluable and followed for 15 months (7-52 months). 24 (92.3%) patients recovered (CR), 1 (3.8%) had a partial remission (PR), and 1 (3.8%) was not effective (NR). Patients who failed or relapsed were treated with laser, radiotherapy or surgery and all achieved CR. temporary adverse effects included edema, pain, hoarseness and skin phototoxicity. Therefore, PDT is considered an effective and safe treatment for abnormal growths and early carcinomas of the oral cavity and larynx.
Biel [6] also published 115 patients with stage T1 and T2 laryngeal cancer who received PDT and had 91.3% CR after single treatment.
PDT can achieve a radical effect for early stage laryngeal cancer, while it needs to be combined with ablative therapy for advanced laryngeal cancer, which can achieve a palliative effect. The author has treated 6 cases of advanced laryngeal cancer and all of them reached PR.
3.Tracheal-bronchial cancer
(1) Indications
Radical treatment: mainly used for early stage lung cancer and precancerous lesions, if the lesion is superficial and <1cm in diameter; the lesion can be seen under endoscopy and the tumor site can be aligned with fiber optics. There is no distant hematologic or lymph node metastasis. < p="">
②Palliative treatment, mainly used for the treatment of advanced stage lung cancer, firstly, ablation therapy is used to drive away the tumor in the lumen, unblock the ducts and improve the respiratory function, and then PDT is used to destroy the residual tumor, and some patients can obtain disease control and create conditions for surgical resection.
③Local residual or recurrent small lesions after surgery and radiotherapy.
④Application with laser, electrocoagulation, freezing, radiotherapy, chemotherapy, etc.
(2) Curative effect
The efficacy of PDT is significantly correlated with tumor diameter [7]. For early-stage lung cancer with tumor diameter <1 cm, the recent clinical cure rate after PDT reached 90%, and 26 cases were followed up after PDT: 9 cases died of other causes, only 1 case died of cancer recurrence, and 16 cases survived tumor-free, among which 3 cases survived for more than 5 years. However, for lung cancer patients with tumor diameter >1 cm, multiple endobronchial lesions, and occlusion of the lumen, the recurrence rate of stump cancer was 23%. Although stump cancer is still initially effective for PDT, the recurrence rate is still as high as 75%. Therefore, PDT should be combined with radiotherapy or Nd:YAG laser treatment for patients with obstruction in the distal bronchial segment in order to achieve better treatment results.
In Japan, 264 lesions treated with PDT were reported and divided into four groups: tumor maximum diameter <0.5 cm="" 0.9="" 2.0="" >2.0 cm group, CR was 94.4%, 93.5%, 80% and 44.1%, respectively, indicating that tumor size and depth were significantly correlated with efficacy. Recently, endotracheal ultrasound was used to develop PDT treatment plans and evaluate the efficacy. The use of blue fluoroscopic bronchoscopy can also accurately diagnose and define the extent of Tis and the depth of subcutaneous cancer in the bronchial mucosa. It can also be used to determine the outcome after treatment. For extensive lesions (from proximal to distal bronchus, or more than one lung segment or contralateral lung as well), PDT is more appropriate. It can be used both as a stand-alone treatment option and as a pre-surgical treatment option to reduce the tumor and narrow the scope of surgery. PDT is suitable for 80-85% of patients with advanced lung cancer and can achieve PR or CR, especially in patients with respiratory distress. For patients with intracavitary obstruction, PDT is as effective as thermal ablation and lasts longer. stage IV patients with poor PS are not suitable for PDT. 2-year survival rate is 40% for patients with PS <2< strong="">, but only 5% for patients with >2. Early superficial lung cancer is the preferred index for PDT: those who are not suitable for surgery or refuse surgery, residual tumor infiltration or recurrence in the trachea, multiple tumors.
For early central lung cancer with tumor diameter >1 cm, the efficacy of the first-generation photosensitizer Photofrin is limited, and in recent years the second-generation photosensitizer NPe6 (absorption wavelength of 664 nm) has been applied in Japan with very good efficacy.Usuda reported [8] that in 70 cases with tumor diameter ≤1.0 cm and 21 cases with tumor diameter >1.0 cm, CR with NPe6-PDT were The CR was 94.0% (66/70) and 90.4% (19/21) after NPe6-PDT. The large tumors in the airway were first removed by high-frequency electrosurgery and then followed by NPe6-PDT, which was also effective in eliminating the residual tumors.
Moghissi [9] also reported sequential treatment with Nd:YAG and PDT. The large intracavitary tumors were first removed with the Nd:YAG laser, and then the residual tumors were destroyed with PDT 4-6 weeks later. The degree of symptom improvement and survival rates were better than those of the PDT and Nd:YAG groups alone. Some patients with small cell lung cancer treated with both chemotherapy and PDT have obtained excellent treatment results.
Based on a large number of Meta-analyses, many authors recommended [10] the following regimens to be selected in early-stage lung cancer (according to the weighting factor, from B → I optional regimens are mitigated accordingly).
(i) For those early superficial, inoperable squamous carcinomas, PDT should be used as a treatment option with recommendation B.
② For those early superficial, operable squamous carcinoma, PDT can also be used as a treatment option, but further comparison of the advantages of both is needed, recommendation I.
③ For those early superficial squamous carcinoma, high-frequency electrodesiccation should be used as a treatment option, recommendation C.
④ For those early superficial squamous carcinoma, freezing should be used as a treatment option, recommendation C.
⑤ For those early superficial squamous carcinoma, brachytherapy should be used as a treatment option, recommendation C.
⑥ For those early superficial squamous carcinomas, Nd:YAG laser should not be used as a treatment option, recommendation I.
For diffuse intraluminal tumors, APC may also be used to eliminate larger tumors before placing endotracheal stents. In cases of recurrence with endoprosthesis placement, APC may also be used to remove the tumor, followed by PDT to further eliminate the residual tumor. However, the endoprosthesis can block the laser penetration, so it is better to perform PDT before endoprosthesis placement.
The author has reported [11] 20 cases of advanced tracheobronchial carcinoma, and for larger tumors in the lumen, APC was used to ablate them first, followed by PDT 1 week later to eliminate their residual tumors, with an efficiency of 100%.
For central type lung cancer with both intraluminal and extraluminal tumors, the combination of APC and Ar-He knife is used to eliminate tumor cells in different parts.
For diffuse intra-cavity tumors or larger tumors, PDT can also be combined with radiotherapy or chemotherapy to obtain synergistic treatment effects. However, the interval between radiotherapy and PDT should be 1 month, either method can be used before PDT, and the combination of PDT and chemotherapy should be preceded or synchronized by chemotherapy, but not after PDT, otherwise the efficacy will be reduced.
Lee [13] reported a case of small cell lung cancer treated with PDT and then combined with radiotherapy and chemotherapy to achieve CR, with no recurrence at 2 years follow-up.
(2) Contraindications.
① Hematoporphyria and other diseases worsened by light.
(2) Known allergy to porphyrins or to any excipients.
(3) Tumor has invaded large blood vessels and adjacent major blood vessels.
④People who are scheduled to undergo surgical treatment within 30 days.
⑤ Those who have ophthalmic disease requiring light examination within 30 days.
⑥Currently undergoing treatment with photosensitizers.
(⑦Tumor at an inaccessible site of fiber optics.
(8) Those with tracheal tumors causing severe stenosis.
(3) Major complications.
(i) Perforation: formation of mediastinal fistula by necrosis of tumor tissue after PDT.
(ii) Bleeding or obstruction: necrosis and detachment of the mass and bleeding from the trauma.
After necrosis and detachment of the mass, the texture is brittle, and the necrosis can be combined with freezing to remove the necrosis.
(iii) Stenosis: localized fibrotic scar formation of stenosis after PDT.
(iv) Acute mucosal edema: bronchial and laryngeal edema causing airway obstruction within 48h after PDT.
van-Boxem [12] compared the extent of tracheal wall scarring seen microscopically and subepithelial fibrosis of the mucosa seen on tissue biopsy in 17 patients with bronchial carcinoma who underwent bronchoscopic electrocautery (BE) alone, 6 cases of PDT and 6 cases of Nd-YAG laser irradiation. The results showed that 29% of the tracheal wall was significantly scarred after treatment in the BE group (one case with >50% lumen narrowing), 67% in the PDT group with significant lumen narrowing, and 83% in the Nd-YAG group (one case with significant lumen narrowing). The wall biopsy revealed moderate to severe fibroblast hyperplasia in 7% of the BE group, 60% and 67% of the PDT and Nd-YAG groups, respectively; excessive stromal hyperplasia in 0%, 40% and 50% of the three groups, respectively; and dense collagen formation in 12%, 40% and 33% of the three groups, respectively. Airway scarring and subepithelial fibrosis were more pronounced in the PDT and Nd-YAG groups compared with the BE group. Appropriate methods should be selected clinically.
4.Pleural and peritoneal mesothelioma
PDT combined with surgical resection can significantly improve the outcome. Moskal et al [14] reported 40 cases in which surgical resection was performed first, followed by intra-thoracic PDT. the median survival of the whole group was 15 months, and the 2-year predicted survival rate was 23%, including 36 months and 61% for stage I and II patients, respectively, indicating that PDT in concert with surgery was effective in improving treatment outcomes.
The author treated a case of malignant pleural mesothelioma with argon knife combined with photodynamic therapy under tracheoscopy instead of thoracoscopy, and the patient recovered well 3 days after surgery, with reduced breathlessness, increased appetite, and the ability to move on the floor. He survived for 8 months.
5.Other
PDT plays a good role not only in malignant airway diseases, but also in benign diseases. In refractory benign granuloma, PDT can destroy the nascent granulation tissue and reduce recurrence. In infectious diseases, Korean scholars have used it to treat bacterial infection of maxillary sinus with good results. The author has used PDT to treat a patient with laryngeal cancer with bronchial tuberculosis, and PDT was performed at both sites at the same time, resulting in PR for laryngeal cancer and CR for bronchial tuberculosis.
IX. Technical outlook
PDT can achieve curative effect on early central lung cancer or precancerous lesions. Therefore, early diagnosis of lung cancer is very important, and PDT is preferred in combination with advanced technical means such as fluorescence bronchoscopy or narrow-wave light bronchoscopy and ultrasound endoscopy, which can improve the cure rate. For late advanced stage, it is necessary to combine ablation therapy to remove the intraluminal tumor first, and then combine with PDT, which can destroy the residual tumor. In recent years, new photosensitizers such as NPe6 and photosensitizers with two photon absorption peaks [15] can significantly increase the depth of destruction of PDT, which can also be very effective for larger tumors in the cavity. At present, all photodynamic therapy machines are single wavelength machines, and in the future, lasers with multiple wavelengths will be produced. The direction of development of photosensitizers will be drugs with multiple absorption peaks and longer wavelengths, allowing deeper irradiation. At the same time, minimizing skin phototoxicity, with no light avoidance and short-term absorption is preferred.