Extended necrosis of the oesophageal wall after photodynamic therapy: Report of two cases

We report two cases of extended necrosis of the oesophageal wall after photodynamic therapy for small recurrence of oesophageal carcinoma which had first been treated by radiotherapy. The possible cumulative effect of radiation injury and photodynamic therapy on the circulation of the oesophageal wall are discussed. These two cases may suggest caution in treating previously irradiated patients with photodynamic therapy.     

Salvage esophagectomy for local recurrent esophageal cancer after definitive chemoradiotherapy followed by photodynamic therapy: A case report

IntroductionPhotodynamic therapy (PDT) is performed as a salvage treatment for patients with residual or recurrent esophageal cancer after chemoradiotherapy (CRT). Although PDT is considered less invasive than salvage surgery, it is unclear how deep its effects are and whether it causes damage to adjacent tissues. Herein, we report a case of esophageal cancer treated with PDT followed by esophagectomy. In this case, we evaluated the effect of PDT on adjacent tissues based on surgical and pathological examination.Presentation of caseA 58-year-old man with dysphagia was diagnosed with esophageal squamous cell carcinoma (SqCC; T1N0M0, Stage I) in the upper thoracic esophagus. He underwent definitive CRT with two courses of 5-fluorouracil and cisplatin every 4 weeks with 60 Gy of radiation. Twelve months after CRT, endoscopic examination revealed local recurrence, and PDT using talaporfin sodium was performed. The tumor recurred again 6 months after PDT, and robot-assisted thoracoscopic esophagectomy was performed as a definitive treatment. Tissues around the left side of the esophagus and thoracic duct were tightly adherent with severe fibrosis and were successfully removed by extended resection. Histopathological examinations showed that the esophageal wall and peri-esophageal tissue were replaced by fibrous tissue and this extended even beyond the tumor.DiscussionThe primary tumor was limited to the submucosal layer, and the target for irradiation had some longitudinal margins. Therefore, PDT can cause intense inflammation in tissues adjacent to the tumor.ConclusionsIt is necessary to consider the location when performing salvage esophagectomy after PDT.     

Photodynamic therapy in gynaecological cancer

Tumour recurrences in the gynaecological field after conventional therapy are a big problem because there is little choice for other therapies without inflicting further damage. Photodynamic therapy (PDT) is indicated because it is selective and without side-effects in flat or small recurrences.We treated 15 patients with vaginal and vault recurrences of cervix carcinoma, adenocarcinoma in the corpus uteri and rectum. The PDT was performed after 24–48 h with Hp, 5 mg/kg body weight, injection, and an argon-dye laser for 13 cases, tungsten and xenon lamps in 2 cases. All patients were previously treated with conventional therapy (i.e. surgery, radiotherapy, chemotherapy). Doses ranged from 60 to 500 J cm^–2. The results were: 8 complete local responses, 6 partial responses, 1 no change. Four patients died because of distant metastases or progression. One partial response was treated with brachytherapy and is now disease free. All the other patients are still living. In all cases we have seen no side-effects from PDT. The patients were sheltered from the sunlight for 20–30 days after therapy.     

Photodynamic therapy for cholangiocarcinoma

The prognosis of nonresectable cholangiocarcinoma is dismal, and in Bismuth type III and IV tumors relief of jaundice is seldom achieved, despite successful endoprosthesis insertion. Therefore, we evaluated additional photodynamic therapy in patients who failed to respond to endoprostheses insertion. All patients showed good clinical results in regard to jaundice, quality of life; and survival time (median, 439 days). Before initiating a randomized multicenter trial we wanted to evaluate these preliminary results in a greater number of patients. Twenty-one patients underwent photodynamic therapy in addition to endoscopic drainage. The hematoporphyrin derivative Photofrin was infused intravenously (2 mg/kg body weight), and intraluminal photoactivation was performed 2 days later. Bilirubin decreased from a mean level of 201.26 ± 189.25 μmol/l after stenting alone to 68.87 ± 78.27 μmol/l (P = 0.0051), and the Karnofsky index improved from 49.04% ± 28.79% to 72.85 ± 19.01 (P = 0.003). Thirteen patients have died and 8 patients are still alive, with a follow-up period of 82–739 days. The 6-month survival time is 95%. Similar results were obtained by another group, with 75% overall (stage M1 and M0) survival after 6 months and beyond 80% for stage M0. Other authors treated 7 patients and saw a remarkable reduction of bile duct stenosis and bilirubin decrease in all patients. Received: September 5, 2000 / Accepted: October 26, 2000     

Management of oesophageal cancer

Oesophageal cancer is a disease of dismal prognosis. There are variations of epidemiology among different ethnic groups and geographic regions. India is a country with high incidence. This can be attributed to the interplay between environmental, dietary factors and life-style of the population of the country. Optimal therapeutic strategy for patients with oesophageal cancer demands individual consideration. Majority of oesophageal cancer patients present at an advanced stage of disease. Screening programmes or strategies aiming at early diagnosis can improve the prognosis; unfortunately this is not cost-effective except in very high incidence areas. Accurate staging can help select the most appropriate treatments, such as excluding those patients with metastatic disease who are unlikely to benefit from surgery, and treating very early lesions with endoscopic means. When surgery is indicated, treating patient in a high-volume centre can improve the outcome and minimise complications. Although surgical resection remains the main treatment modality, long-term prognosis after surgical resection alone has been suboptimal except in those with early disease. Multidisciplinary approaches including chemotherapy and radiotherapy with or without surgery are increasingly employed for patients with advanced disease. Collaboration among surgeons, clinical oncologists, radiologists and physicians is of utmost importance to achieve the best results. Treatment for patients should be individualised to enhance outcome.     

Photodynamic therapy of esophageal carcinoma

Summary Photodynamic therapy (PDT) utilizing either hematoporphyrin derivative or Photofrin II is proving to be an effective modality in the treatment of early superficial (ES) or advanced invasive (AI) carcinoma of the esophagus. An argon-pumped dye laser was used to deliver 630 nm light via quartz fibers passed through the biopsy channel of a gastroscope after intravenous injection of photosensitizer. Between 1982 and 1989, 20 patients (ES=6; AI=14) were treated in this manner. Complete remission was obtained in 4 of 6 ES cases, and the mean survival after PDT alone or in combination with other therapy was 27 months. Five patients remain alive to date. In the AI group, significant remissions were obtained in 6 cases while partial remissions were observed in another 8. The mean dysphagia grade improved from 4.0 to 2.8. We conclude that PDT is efficacious in the treatment of ES esophageal cancer, where complete remission may be achieved, and as palliative therapy in advanced cases to alleviate dysphagia.     

光动力治疗裸鼠胰腺癌及其机理的实验研究

目的 探讨在裸鼠胰腺癌瘤内注射光敏剂血卟啉衍生物（HpD）、竹红菌甲素（HA）及2－丁胺－2－去甲氧基竹红菌甲素（2－BA－2－DMHA）后，光动力治疗（PDT）的效果及其作用机理。方法 将人胰腺癌细胞株SW1990接种到裸鼠皮下，建立胰腺癌动物模型，而后将光敏剂HpD、HA及2－BA－2－DMHA注射入肿瘤，再用激光照射肿瘤局部，观察PDT治疗胰腺癌的效果。另以第Ⅷ因子为标记，采用免疫组化LSAB法研究肿瘤血管损伤的情况。结果 PDT对胰腺肿瘤有明显杀伤作用，能使胰腺肿瘤生长速度明显减慢。免疫组化染色明显，PDT可引起血管内皮细胞损伤和血管结构破坏。结论 PDT对胰腺癌有治疗作用，血管损伤是其杀伤肿瘤的重要途径。     

Impact of FDG-PET for staging of oesophageal cancer

Background and aims Treatment of oesophageal cancer depends on staging and the general health of the patient. In stages I–II b, as well as in some stage III diseases, surgical resection remains the therapy of choice for cure, but a curative approach is not possible in stage IV. In our hospital we give preoperative radio-chemotherapy to all patients with an oesophageal cancer T>1, Nx, M0. Therefore, the main purpose of the clinical staging of oesophageal cancer is the exclusion of M1 and T4 disease with infiltration into the tracheobronchial system or the aorta. The aim of the investigation was the assessment of positron emission tomography for detection of M1 disease.Patients/methods Between 1998 and 2002, 84 patients with oesophageal cancer (64% squamous cell carcinoma and 36% adenocarcinoma) were enrolled into the study. Of these, 48.8% were operated on; 35.7% of the patients were not operated on, for oncological reasons, 7.1% for medical reasons, 3.6% chose not to be operated on, and, for unknown reasons, 4.8% were not operated on.Results Twenty-five patients had stage IV disease or additional, synchronous cancer of the head and neck (n=2). As the only investigational procedure, positron emission tomography revealed M1 stage in 11 of 25 patients (44%). In 13/25 (52%) both computed tomography and positron emission tomography revealed stage IV disease. False positive results by positron emission tomography were observed in three patients. The sensitivity and specificity of positron emission tomography (PET) was 0.96 and 0.95, respectively. Most of the metastases detected by PET only, were localised within the neck, liver and bone. With regard to the 66 of 84 patients deemed medically fit for operation and without local infiltration into the tracheobronchial system (T4) PET as the only imaging procedure changed the therapeutic strategy in 11 of 66 (16.6%) patients with to M1 disease.Conclusion Our results demonstrated clearly the impact of the PET scan for decision-making in patients with oesophageal carcinoma. PET should be performed prior to therapy with curative intention. However, addition of a computed tomography scan of the neck might reduce the rate of unexpected metastases detected by PET.     

Photodynamic therapy of 168 early stage cancers of the lung and oesophagus: a japanese multi-centre study

In 1994, the Ministry of Health and Welfare of Japan approved photodynamic therapy (PDT) for the treatment of early stage lung cancer (T0 and T1), superficial oesophageal cancer, superficial early stage gastric cancer and carcinoma in situ and/or dysplasia of the cervix. The decision to do so was based on studies carried out by the PDT Research Group of the Ministry, including PDT treatment of 168 early stage central lung cancers (123 superficial lesions and 45 nodular lesions) and 32 superficial oesophageal cancers. The results presented in this article were analysed according to the extent of the lesion. Of the 123 superficial lung cancers, complete remission (CR) was obtained in 93% of 89 lesions less than 1.0 cm in diameter. Larger lesions responded less well. Complete remission was obtained in 97% of the 33 superficial oesophageal cancers, although three of six patients with lesions over 3.0 cm in diameter later died of metastatic disease. The authors believe PDT to be a suitable and effective treatment for early stage lung and oesophageal cancers.     

Endoscopic photodynamic therapy in lung cancer

The main purpose of cancer therapy is to treat malignant tissue with the least damage to normal surrounding structures. Photodynamic therapy (PDT) seems to be able to fulfil this simple but fundamental premise.The mechanism of action of the photosensitizer—light system can be summarized in two main points. Chiefly, it seems to be a photodynamic process, with energy transfer from the light to the photosensitizer and from it to the oxygen molecules. Oxygen is excited and becomes singlet oxygen, which is extremely reactive and very noxious for tissues in which it develops. Secondly, a thermal mechanism related to light absorption and consequent temperature rise also seems to be involved in malignant necrosis by PDT.Thirteen males were submitted to endoscopic PDT. A total of 15 treatments were given: 2 patients were submitted to 2 sessions of PDT. Forty-eight hours after HPD administration (72 h in a few cases), the lesions were exposed to a 630 nm light from an argon-dye laser system.The total estimated energy dose delivered to the tumour surface was 90–150 J/cm² in 11 cases. All cases treated responded well and total disappearance was obtained. Median follow-up was 9.5 months (1–20 months) and the estimated energy delivered from 90–600 J/cm². No major complications were reported.     

Photodynamic therapy of malignant brain tumours

Experience with intraoperative PDT in 50 patients with malignant supratentorial tumours is reported; in 33 cases the tumour was recurrent. In 45 patients the tumour was a cerebral glioma and in five cases a solitary cerebral metastasis. There were 29 males and 17 females with an age range of 17–73 (mean 48) years. All patients received either haematoporphyrin derivative (HPD) or dihaematoporphyrin ether (DHE) 18–24 h preoperatively. A photoilluminating device, of the authors' design, was coupled to an argon dye pump laser in order to deliver light at 630 nm to a tumour cavity created by radical tumour resection and/or tumour cyst drainage. The total light energy delivered ranged from 440 to 3888 J and the light energy density ranged from 8 to 175 J/cm². In eight patients a line fibre(s) was used to administer interstitial light as a supplement to the cavitary photoillumination. The additional light dose ranged from 60 to 945 J/cm.There were two postoperative deaths as the consequence of haematoma accumulation in the tumour resection cavity. In three patients neurological function was worse postoperatively and did not recover. Postoperative cerebral oedema was pronounced in some cases and required second craniotomy in two patients (the histology from both showed haemorrhagic necrosis of residual tumour). Four patients developed wound infections; two of these required surgical treatment. Four patients, two of whom were hemiparetic, developed deep vein thrombosis and required anticoagulant therapy. There were no adverse systemic reactions to the administration of either photosensitizer and only three skin photosensitivity reactions.Follow up ranged from 1 to 30 months. In the group of 45 patients with gliomas the death rate per observation year was 0.92 for the interval between PDT and death. For the interval between first diagnosis and death the rate was 0.41 deaths per observation year. The median survival was 8.6 months with a 1 and 2 year actuarial survival rate of 32% and 18%, repectively.In 12 patients a complete or near complete CT scan response was identified post PDT. These patients tended to have a tumour geometry (e.g. cystic) that allowed complete or near complete light distribution to the tumour. The median survival for this group was 17.1 months with a 1 and 2 year actuarial survival of 62% and 38%, respectively. In the 33 cases without a complete response the median survival was 6.5 months with a 1 and 2 year actuarial survival of 22% and 11%, respectively.Photodynamic therapy of malignant brain tumours can be carried out with acceptable risk. Good responses appear to be related to adequate light delivery to the tumour.     

Comparison of endoscopic laser therapy and self expanding metal stents for palliation in patients with non-resectable oesophageal carcinoma

Background

There are currently limited data on the comparative success of endoscopic laser therapy (NLT) and self expanding metal stents (SEMS) as palliative measures in patients with non-resectable oesophageal cancer. This study aims to assess and compare the outcomes of these methods of endoscopic palliation.

Photodynamic therapy for the treatment of advanced gastrointestinal tumours

In the study, 120 patients with advanced gastrointestinal tumours were treated by PDT; 5 mg/kg of HpD was intravenously given 48–72 h prior to PDT. The light source was an argon dye laser with an output beam of 630 nm. The irradiation time varied from 15–25 min with a power of 100–350 mW cm^–2. The entire tumour was irradiated with a light dose of 100–250 J cm^–2. Of the 120 patients, 20 had cancer of esophagus, 72 had cancer of the gastric cardia, 18 had cancer of the stomach and 10 had cancer of the rectum. Eighty-eight patients (73.3%) had a response to PDT. Twelve patients with CR were followed up for one to five years, two patients died during the two years after PDT.     

Intraoperative photodynamic therapy as an adjunct to surgery for recurrent rectal cancer

Background: Locally recurrent rectal cancer is a difficult management problem for the surgical oncologist. Current therapies including radical surgery, radiation and chemotherapy have had little success in producing curative results for these patients. This study incorporated intraoperative photodynamic therapy (PDT) as an adjunct to radical surgery for the treatment of locally recurrent rectal cancer. Methods: Twenty-two patients were enrolled in a prospective feasibility study and injected with Photofrin (Quadra Logic Technologies, Vancouver, British Columbia, Canada) before surgery. Eight patients were found to be candidates and received PDT after surgical exploration and resection. Seven patients had rectal adenocarcinoma and one had squamous cell carcinoma of the anal canal. Results: Based on the indication for PDT, three patient groups were evaluated: group A, resection of all gross disease with negative pathologic margins in four patients; group B, resection of gross disease with positive pathologic margins in two; and group C, residual bulky tumor in two patients. There was one perioperative death (12.5%), not related to PDT, and one major morbidity due to PDT (12.5%). Local recurrence occurred in six patients (two in group A, two in group B, two in group C). Mean overall survival was 15.4 months for group A, 6.5 months for group B, and 24.5 months for group C. Conclusions: The results of this study suggest that intraoperative PDT may be administered safely in patients undergoing resection of recurrent rectal cancer. However, its use in the present state of technology appears to be inadequate for control of disease, particularly if bulky tumor or residual microscopic disease is left behind. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Photodynamic therapy of tumours in gastroenterology—a review

Photodynamic therapy (PDT) is the local destruction of tissue by the interaction of light with a previously administered photosensitizer producing a photochemical effect. This technique has been demonstrated to permit the eradication of small tumours in experimental and clinical practice, with clear biological advantages. This paper reviews PDT experience in gastroenterology, together with concepts currently under experimental investigation.     

Photodynamic therapy in gastrointestinal cancer.

Six patients with an early stage of gastrointestinal (GI) cancer (T1N0M0, stage I) were successfully treated by photodynamic therapy (PDT) as follows: esophagus-1, stomach-2, rectum-3. The patients were photosensitized 72 hrs prior to treatment with pure hematoporphyrin at a dose of 5.10(-6) kg/kg b.w. in a slow intravenous infusion. Argon-pumped dye laser light at 0.630 microns wavelength was used in single and multiple treatment sessions with the power density ranging from 0.015 to 0.192 W.m-2 and a dose varying from 0.320 to 1.600 kJ.m-2. Tumor eradication (complete response) was obtained in each of the patients. No early or late treatment related complications were recorded. The patients were followed-up in the course of 7-16 months after treatment and no local recurrence or general development of disease (metastases) were reported. PDT in the early stage of GI carcinoma was recognized as a radical therapeutic method in clinical oncology.     

血卟啉光动力作用杀伤人胆管癌细胞的实验研究

目的研究血卟啉化衍生物（hematoporphyrin derivative，HPD）光动力作用（photodynamic therapy，PDT）对人胆管癌细胞QBC939的杀伤效应：方法以人胆管癌细胞系QBC939为研究对象，采用血卟啉化合物作为光敏剂，半导体激光治疗仪为光源。实验分为对照组（空白对照组、单纯光动力组、单纯光敏剂组）和光动力作用组，以系列浓度的血卟啉经不同强度光照后，用MTT法测定PDT对QBC939细胞的相对抑制率和筛选最佳PDT参数。结果光动力作用组的吸光度（OD值）与对照组间的差异具有统计学意义（P〈0.01），随着HPD浓度的增加和光照强度的增大，光动力作用对细胞的相对抑制率逐渐增大。不同的光敏剂浓度和光照强度间组合能达到相同的抑制率，如以10mg／L HPD经5J／cm^2光照强度或以4mg／L HPD经15J／cm^2光照强度对QBC939均可以达到92％相对抑制率。在最佳光照能量密度条件下，设计三组功率-时间组合，组间没有显著差异。结论1）PDT对人胆管癌细胞QBC939具有明确的杀伤作用，其对细胞的抑制率具有显著的剂量效应关系。光敏剂浓度和光照强度间存在交互关系，从临床角度考虑，采用较低的光敏剂浓度经较大的光照强度照射是理想的PDT治疗方案。2）改变功率时间的组合不会影响光动力对胆管癌细胞杀伤作用，采用在光纤承受范围内的大功率短时间的照射方式可达到安全快捷的目的。     

m-THPC photodynamic therapy for head and neck cancer

Over the past 30 months, the authors have treated a wide variety of head and neck cancer patients with meta-tetrahydroxyphenylchlorin (mTHPC)-mediated photodynamic therapy (PDT). This drug is a powerful, second-generation photosensitizer with significant advantages over earlier drugs. Treatment ranged from palliation and adjunctive to curative procedures. Results to date are very encouraging, with marked advantages over standard methods of treatment with respect to morbidity, both functional and aesthetic. Potential cure rates remain essentially unchanged, very much dependent on the stage of the tumour. These promising early results justify a multicentre study for treatment of early head and neck cancer using this drug and light combination. This is now underway.     

Photodynamic therapy for the treatment of vertebral metastases in a rat model of human breast carcinoma.

The feasibility and efficacy of photodynamic therapy (PDT) for the treatment of vertebral metastases using a minimally invasive surgical technique adapted from vertebroplasty was evaluated in a rodent model. Initial validation included photosensitizer (benzoporphyrin-derivative monoacid-ring A) drug uptake studies and in vitro confirmation of PDT efficacy. Intracardiac injection of human MT-1 breast cancer cells was performed in athymic rats. In 63 rats that developed vertebral metastases 21 days post-inoculation, single treatment of PDT was performed using a parapedicular approach placing an optical fiber adjacent to targeted vertebrae. Two milligrams per kilogram of photosensitizer drug was administered intravenously followed by 150 mW of 690 nm light illumination at varying drug-light intervals and light energies. Histologic and immunohistochemical analysis was performed assessing treatment effect. Local tumor viability and growth was quantified by bioluminescence imaging pre and 48 h post-treatment. PDT demonstrated an ablative effect on vertebral metastases (light energies 25-150 J). The effect varied in proportion to light energy with the greatest anti-tumor effect observed at 150 J using a 3 h drug-light interval. 9/22 rodents in the 3 h drug-light interval developed hindlimb paralysis following treatment, consistent with drug uptake studies demonstrating an increase in spinal cord uptake 3h following drug administration. The observations of paralysis following treatment highlight the importance of closely defining the therapeutic window of treatment in safety and efficacy.     

Primary gastric cancer in an oesophageal gastric graft after oesophagectomy

Objective: Recent advances in surgical treatment of oesophageal cancer have improved the prognosis of early, locally advanced oesophageal cancer. Primary cancer from oesophageal graft is rare, but has been detected in long-term survivor. We analyzed data from patients who developed primary gastric cancer in an oesophageal graft to evaluate strategies of treatment and their outcomes. Methods: We retrospectively reviewed data from patients who developed primary gastric cancer in oesophageal graft at Samsung Medical Center between September 1994 and December 2009. The clinico-pathologic features and prognoses were investigated. Long-term survival rate was determined by Kaplan–Meier analysis. Results: Ten primary gastric graft cancers (five early gastric cancer (EGC), five advanced gastric cancer (AGC)) were diagnosed. The mean age was 69.0 (range 59.6–74.6). Initial operation was Ivor-Lewis transthoracic oesophagectomy in eight cases and three-field lymphadenectomy in two. The median period to detection of the primary gastric graft cancer after oesophagectomy was 50 (9–102) months. Seven gastric graft cancers were diagnosed by regular endoscopic examination. EGCs were treated with ESD in two cases, partial resection of stomach in one, and oesophagocolojejunostomy in three, including one patient who underwent the operation after ESD. AGCs were treated with chemotherapy in one case, supportive care in one, and oesophagocolojejunostomy in three. There was no adjuvant chemotherapy used in any case. The median follow-up period after second operation was 14 months (range 1–97). Six patients survived during this period. Three of the five AGC patients died. The estimated 5-year survival rate of our cases was 70%. Conclusions: In areas of high prevalence of stomach cancer, regular endoscopic examinations of oesophageal gastric grafts may help in the early detection of primary gastric graft cancer. Reoperation with a colon graft is a potential treatment option for primary gastric graft cancer.