Does PDT have potential in the treatment of COVID 19 patients?

The corona virus pandemic has ignited a proliferation of research aimed at prevention of spread, early diagnosis and treatment. Coincidentally, in recent years the Yorkshire Laser Centre has been engaged in developing the methodology of applying PDT in chronic bronchiectasis. Our methodology is based on Methylene Blue (MB) mediated PDT used topically within the airway. The novelty of the method is the use of a nebulizer to deliver the photosensitizer. We suggest that our protocol and methodology could be modulated for use in respiratory infections of COVID -19.

A Surgical View of Photodynamic Therapy in Oncology: A Review.

Clinical photodynamic therapy (PDT) has existed for over 30 years, and its scientific basis has been known and investigated for well over 100 years. The scientific foundation of PDT is solid and its application to cancer treatment for many common neoplastic lesions has been the subject of a huge number of clinical trials and observational studies. Yet its acceptance by many clinicians has suffered from its absence from the undergraduate and/or postgraduate education curricula of surgeons, physicians, and oncologists. Surgeons in a variety of specialties many with years of experience who are familiar with PDT bear witness in many thousands of publications to its safety and efficacy as well as to the unique role that it can play in the treatment of cancer with its targeting precision, its lack of collateral damage to healthy structures surrounding the treated lesions, and its usage within minimal access therapy. PDT is closely related to the fluorescence phenomenon used in photodiagnosis. This review aspires both to inform and to present the clinical aspect of PDT as seen by a surgeon.

Photofrin PDT for early stage oesophageal cancer: long term results in 40 patients and literature review.

BACKGROUND: Yorkshire Laser Centre experience of PDT in early oesophageal cancer (EOCa) to determine long survival at 3 and 5 years (absolute) and factors which might influence outcome. MATERIAL/METHOD: The records of patients who had PDT (1997-2009) for oesophageal cancer were reviewed and those with EOCa were studied and analysed. All patients had standard work up and staging. PDT was carried out using Photofrin 2 mg/kw bw, iv followed 24-72 h later by endoscopic illumination with 630 nm laser light. Results were assessed based on pathological response to treatment and survival at 3 and 5 years post-PDT. RESULTS: There were 40 patients with EOCa amongst 144 who had PDT for oesophageal cancer. 30 male and 10 female (mean age 77, range 48-84). 35 had adenocarcinoma and 5 squamous cell carcinoma. 20 of the former had Barrett's mucosa. There was no operative or 30-day mortality and no serious complications. Adverse effects were noted in 10 patients including 2 with skin photosensitivity and 3 with mild stricture requiring one dilatation. The median follow up was 76.1 (range 36-150 months). In this period 24 patients have died between 2 and 150 months (median 41 months). 16 patients are alive in between 36 and 110 months. 3 and >or=5 years or more survival (absolute) were 72.5% and 53.8%, respectively. CONCLUSION: Endoscopic PDT should be considered as the treatment of choice in patients with EOCa who are ineligible for surgical resection. We suggest that a carefully designed study of a cohort of patients with EOCa comparing surgical resection with endoscopic PDT is warranted.

Update on the current indications, practice and results of photodynamic therapy (PDT) in early central lung cancer (ECLC).

OBJECTIVES: The aim of this study was to investigate the practice and results of photodynamic therapy (PDT) in early central lung cancer (ECLC) based on the review of the literature and personal experience and to suggest the future role of PDT in such patients. MATERIAL AND METHODS: Literature search was made for articles on PDT in lung cancer. Only original articles with >10 patients with ECLC treated by PDT were selected. Data collection aimed at providing information on number of patient/lesions in the series, photosensitisers used, illumination method, mortality and morbidity, pathological response to treatment and survival. RESULTS: Fifteen articles (626 patients/715 lesions) were selected. Indication for PDT in the majority had been ineligibility for operation. The drug of choice was Photofrin followed by bronchoscopic illumination using a laser light after an interval of 48-72 h. There was one (0.15%) single death in the whole series. Adverse events consisted mainly of photosensitivity skin reaction (sunburn) 5-28% followed by respiratory complications 0 -18% and non-fatal haemoptysis 0-7.8%. Complete response was recorded in 30-100% for 2-120 months. Five-year survival was 61% (estimated) for those series which have provided the survival data. The analysis highlighted the presence of multifocal lesions in ECLC patients. CONCLUSIONS: Currently, the generally accepted indication of PDT in ECLC is for patients ineligible to/or unsuitable for resectional surgery. It achieves a high rate of complete response (CR) and long-term survival. In the future PDT will find its role in patients with ECLC and multifocal lesions.

Autofluorescence bronchoscopy in volunteer asymptomatic smokers.

We assess the sensitivity of autofluorescence bronchoscopy (AFB) compared to that of white light bronchoscopy (WLB) for identification of pre-invasive neoplastic changes of bronchial mucosa in asymptomatic heavy smokers. WLB was performed using a standard flexible fibre-optic bronchoscope, and AFB carried out using the Xillix LIFE Lung((R)) system. Positive AFB images were indicated in the bronchial tree from 51 of the 93 subjects in the study. Biopsies showed epithelial abnormalities in 27 (15 metaplasia, 12 inflammatory changes) of these. WLB showed abnormality in 1 subject but with no pathological changes revealed by cyto-histology. Therefore, the sensitivity of AFB to metaplasia was 75% compared to zero for WLB. AFB yields positive predictive values for metaplastic and overall mucosal changes of 29.4% and 52.9%, respectively. In summary, over 16% of asymptomatic smokers had metaplastic changes in their bronchial mucosa, and AFB proved more sensitive in revealing early changes than WLB.

Adeno-carcinoma of the pharyngo-oesophageal junction and cervical oesophagus in a patient with an oesophagus lined entirely by columnar epithelium report of a case treated by photodynamic therapy (PDT).

A case of adenocarcinoma in the pharyngo oesophageal junction extending to the upper cervical oesophagus is described. In this case the neo-plastic changes had occurred from columnar epithelium of gastric and intestinal type: Barrett's oesophagus. The Barrett's mucosa involved the whole length of the oesophagus. Because of the general condition of the patient and advanced stage of the tumour surgical treatment was considered inappropriate. Endoscopic Photofrin Photodynamic Therapy was used with good palliation of dysphagia. The patient survived for 9 months, dying form carcinomatosis and oesophago-airway fistula. As far as can be documented only one such case has been previously reported in the literature.

Fluorescence photodiagnosis in clinical practice.

Fluorescence diagnosis has become an important method of investigation in clinical practice particularly in identification and localisation of pre and early cancerous lesions as well as image guided therapy. The method relies on the principle of differential fluorescence emission between abnormal and normal tissues in response to excitation by a specific wavelength of light within the visible spectrum range. In clinical practice two types of fluorescence diagnostic methods are used, namely autofluorescence and drug-induced fluorescence. The former relies on the differential fluorescence of "native" fluorophores whereas the latter requires a photosensitiser which enhances the differential fluorescence emission of the normal versus the abnormal tissues. Development and advances in fibreoptic, endoscopic instrumentation currently permit fluorescence endoscopy to be carried out in a number of situations.

Current indications and future perspective of fluorescence bronchoscopy: a review study.

BACKGROUND: Autofluorescence bronchoscopy (AFB) was introduced into clinical practice early in the 1990s for identification and localisation of intra-epithelial pre-neoplastic (dysplastic mucosa) and early neoplastic (carcinoma in situ) endobronchial lesions. OBJECTIVES: to determine the current range of indications of AFB through review of published literature and to compare sensitivity and specificity of AFB with those of WLB for identification of pre- and early neoplastic lesions in each of the indications. METHOD: Search of the literature produced 62 eligible articles for the review. These were "empirically" classified into five categories: 1. AFB for identification and localisation of early neoplastic changes. 2. AFB for identification and localisation of bronchial neoplastic changes in smokers. 3. AFB for monitoring treatment and surveillance of early neoplastic changes. 4. AFB for identification and localisation of synchronous and multi-focal lesions. 5. AFB used as a tool for lung cancer screening. RESULTS: In all categories the sensitivity of AFB was several times greater than WLB in identifying pre-neoplastic and early neoplastic lesions and the specificity of WLB was higher than that of AFB. When AFB was used for identification and localisation of dysplasia and carcinoma in situ its sensitivity was 25-47% (mean 33%) higher than that of WLB. Its specificity was 7-18% (mean 11%) lower than WLB. The ratio of sensitivity of AFB/WLB was highest in every category when the population tested comprised a higher proportion of pre- and early neoplastic lesions than invasive cancer. In such cases there was relatively lower specificity for AFB compared to WLB. CONCLUSION: The review suggests that AFB should be included in routine investigations of patients suspected of having lung cancer, those undergoing lung cancer surgery and in post-treatment follow-up to discover early cancer and/or recurrence. Also, it has to be included in any screening programme protocol.