The effectiveness of intraoperative photodynamic therapy in the complex treatment of stage III and IV nephroblastoma in children

Intrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?

Prophylactic Irradiation of Surgical Tract Sites in the Era of Radical Pleurectomy for Malignant Pleural Mesothelioma

Photodynamic Therapy for Early Stage Central Type of Lung Cancer

Objective To study the application of photodynamic therapy (PDT) for dental caries prevention using whole body luminescence fiber, and to investigate the effects of PDT on the content of Ca and P in rat molar enamel. Method The rat dental caries model was established by inoculating with S.mutans. Eighty male rats were randomly divided into five groups, including three experimental groups: 17 mW (8 mW/cm2) PDT (group A), 34 mW (15 mW/cm2) PDT (group B), 68 mW (30 mW/cm2) PDT (group C), a positive control group: 20 g/L NaF solution (group D), and a negative control group: 0.9% physiological saline (group E). The experimental groups were treated by 40 μg/mL hematoporphyrin monomethyl ether (HMME) and 650 nm diode laser irradiation. The experiments were conducted for 4 weeks. The contents of Ca and P in the molars of each group were measured by inductively coupled plasma emission spectrometry. Results The contents of Ca and P in group B, C and D after PDT were significantly higher than those in group A and E (all P<0.05). The contents of Ca and P in group A showed no significant difference before and after PDT, while those in groups B and C showed significant increase after PDT (all P<0.05). The increment of Ca in group A after PDT was lower than that in group D (P<0.05), while those in group B and C were significantly higher than those in group D (all P<0.05). There was no significant difference in the increment of Ca and P between group B and C after PDT. Conclusions In the range of the experimental parameters, the PDT promoted effect of tooth remineralization is better than 20 g/L NaF. The levels of Ca and P in the tooth enamel can be promoted by PDT treatment, and the contents of Ca and P are related to the pewer of PDT. The effect of low power PDT on the remineralization of enamel is not obvious. The contents of Ca and P in the tooth enamel are increased with laser power of PDT. When the laser power increased to a certain value, the change in contents of the two elements is not obvious. PDT can maintain the tooth remineralization microenvironment. Key words: Photodynamic therapy; Trace elements; Inductively coupled plasma optical emission spectrometer; Remineralization

This study evaluates the effect of intraoperative photodynamic therapy (PDT) using the multiline argon laser (488-514 nm) or the argon-dye laser (630 nm) combined with surgical resection compared with surgical resection alone in reducing the incidence of C1300 neuroblastoma recurrence in mice. In the control groups, surgical resection alone resulted in 86% +/- 12% tumor recurrence. Surgical resection and intraoperative lasing without photosensitizer resulted in 75% +/- 27% tumor recurrence with the argon-dye laser and 55% +/- 18% recurrence with the multiline argon laser. In the treatment groups, surgical resection and intraoperative PDT at 630 nm resulted in 56% +/- 19% tumor recurrence whereas surgical resection and intraoperative PDT at 488-514 nm resulted in 21% +/- 7% tumor recurrence. The cause for the decrease in local recurrence in the control group using the multiline argon laser is unknown, but could it be due in part to hyperthermic effects. Intraoperative PDT was an effective adjunct to surgical resection in preventing local recurrence in this tumor model.

During the period from 2009 to 2021, 93 patients aged 0–11 years (48 boys and 45 girls) with retroperitoneal tumors were treated. There were 66 patients with nephroblastoma and 27 patients with adrenal neuroblastoma among them. As per treatment strategies, the patients were separated into two groups: the control group and the study group. The control group (comparison) received therapy according to the protocols, whereas the study group consisted of patients who received photodynamic therapy (PDT) in addition to the standard treatment. The control group consists of 47 patients with retroperitoneal tumors, including 35 patients with nephroblastoma and 12 patients with adrenal neuroblastoma. The study group included 46 children: 31 patients with nephroblastoma and 15 patients with adrenal neuroblastoma. The 5-year survival rate in the control group was 74.5%, and it was 91.3% in the study group (p = 0.030). Recurrent tumors developed in 14.9% of the patients in the control group, while in the study group, relapse occurred in 8.7% of the patients (p = 0.357). The PDT used in this study for treatment of retroperitoneal tumors improves the results of surgical treatment. It also appreciably increases the survival rate of patients with retroperitoneal tumors. Overall, PDT is a hopeful antitumor approach and can be effectively used in the complex therapy of retroperitoneal tumors in children.

Results of intraoperative photodynamic therapy (IOPDT) in patients with gastric cancer are represented in the article. The study included 240 patients with gastric cancer stage II-IV (Т3-4N0-3M0-1) with evident or suspected peritoneal dissemination who underwent examination and treatment in P.Herzen Moscow Oncology Research Institute. The group 1, the study group, included 140 patients who underwent nominally curative or palliative surgery for locally advanced and disseminated gastric cancer with IOPDT as additional intraoperative intervention for antiblastics and cancer treatment. The group 2, the control group, included 100 patients who also underwent nominally curative or palliative surgery (equal to extent of surgery in patients from the study group) for locally advanced and disseminated gastric cancer and no intraoperative implication of physical or chemical treatment methods. IOPDT did not worsen a course of early post-operative period, did not impact on severity of post-operative complications and was not associated with increase of post-operative mortality. IOPDT allowed for improvement of 1-year and 3-year disease-specifi c survival rates: by 16.1% and 16.7%, respectively. For nominally curative resections, median survival, 1- year and 3-year disease-specifi c survival rates were improved by 14 months, 17.8% and 31.3%, respectively. For R1, R2 resections, IOPDT improved 1-year disease-specifi c survival rates by 16.4%. Additionally, for nominally curative resections IOPDT did not increase the recurrence rate and improved median recurrence-free survival, 1-year and 3-year recurrence-free survival rates by 16 months, 27.2% and 25.4%, respectively.

A factor that might complicate the use of intraoperative photodynamic therapy (PDT) is a possible adverse effect on normal tissue recovery. In this study, rats with experimental skin incisions received intraoperative PDT (10 mg/kg haematoporphyrin derivative, 180 J/cm(2) laser light), immediately followed by closure. Healing was evaluated by tensile strength assessment of the incisions 21 days after PDT. No significant differences between the PDT-treated group and control groups were found. We therefore concluded that with respect to healing of skin incisions in rats, intraoperative PDT is not contraindicated.

Tumours of the head and neck show a high local tumour recurrence rate ranging between 7 and 30% despite combined treatment modalities. To improve these data, photodynamic therapy (PDT) might be used as an additional treatment besides surgery and radio-chemotherapy. Intra-operative PDT has been proposed to "sterilise" the tumour bed after surgical tumour resection in order to kill any remaining tumour cells which are responsible for local tumour recurrences. Often, during head and neck surgery, large blood vessels and important nerve structures are exposed and could potentially be harmed by intra-operative PDT. Despite the fact that mTHPC is the most commonly used photosensitiser for head and neck tumours, there are no data on potential detrimental side effects of intra-operative PDT onto these vital structures. The purpose of this study was to use a maximal treatment protocol in rabbit observing possible damage to the blood vessels and nerve structures and thus judge the most severe event that could happen in patients. In rabbits the large blood vessels and nerve structures at the neck and at the groin area were surgically exposed and treated by mTHPC-mediated intra-operative PDT. Various treatment parameters (drug-light interval, light dosage, follow up interval) were modified in order to find the critical treatment parameters which might cause maximum tissue effects. The intention was to define the most severe clinical complications which could be expected from mTHPC mediated intra-operative PDT. The most severe tissue reactions were found at a drug dosage of 0.3 mg/kg, a drug-light interval of 24 hours and a light dosage of 20 J/cm(2). Complete necrosis was found for the muscles, fat and connective tissue within the entire treatment field. Blood vessels demonstrated severe oedema, media-hyperplasia or loosening of the endothelial layer leading to various degrees of local thrombosis but no break down of the vessel wall or any rupture was noted. Most nerves were altered by a 75% demyelisation but this did not result in any clinical symptoms. Our results have shown that mTHPC mediated intra-operative PDT used with a maximal treatment protocol (very high doses and very short drug-light intervals) has significant histological impact onto all tissue structures, but did not show any clinical symptoms in rabbits. mTHPC mediated intra-operative PDT seems to be a promising and a safe treatment option which could complement existing treatment modalities in order to improve total survival rate of tumour patients.

Objective To evaluate the safety and efficacy of using thalidomide combined with radiochemotherapy for the treatment of esophageal cancer. Methods A total of 102 patients with esophageal squamous cell carcinoma were treated with radiochemotherapy. The level of serum vascular endothelial growth factor (VEGF) was evaluated at 1 week before radiotherapy, 2-3weeks since the beginning of radiotherapy, and 1 week after radiotherapy completed. Patients who showed no change in the level of serum VEGF during radiotherapy, when compared with pre-radiotherapy, were randomly divided into two groups: control group and thalidomide group. Meanwhile, patients with reduced serum VEGF were assigned to the negative control group (reduced VEGF group). Thalidomide group patients were treated with thalidomide during radiochemotherapy, while those from the control group and reduced VEGF group were underwent regular radiochemotherapy. Results A total of 95 patients finished the treatment regimen with complete follow-up data (24 in thalidomide group, 24 in control group and 47 in reduced VEGF group). The main adverse reaction of thalidomide is varing degrees of lethargy. The 1-year and 3-year survival rates of all groups were 68.4% and 51.6%, progression-free survival time were 56.8% and 19.5%, local control rates were 83.6% and 21.3%, and median survival and progression-free survival time were 18.2 and 15.8 months, respectively. No significant differences were found in the survival and progression-free survival curramong control, thalidomide and reduced VEGF groups (P>0.05). Analysis of the locally advanced (stage II and III) patient subgroup showed that the 3-year survival rates of control, thalidomide and reduced VEGF groups were 0.0%, 31.3%, 20.0%, respectively; the 3-year progression-free survival rates were 0.0%, 31.3%, 16.7% respectively. Both two survival rates were significantly higher in the thalidomide group compared to the control group (P<0.05). The level of serum VEGF in all patients of control group and thalidomide group was measured after and during radiotherapy, and significant diffdfences were found between the two groups(P<0.05), which serum VEGF level reduced stable and rising cases were 13, 11, 0 and 4, 15, 5 in control groups and thalidomide group respectiveoy. The 1-year survival rate, 1-year progression-free survival rate of thalidomide group patients who seserum VEGF level was reduced and stable after radiotherapy were 92.3%, 84.6% and 45.5%, 27.3% respectively. The 3-year survival rate, 3-year progression-free survival rate and 3-year local control rate of thalidomide group patients who seserum VEGF showed reduced and unchanged after radiotherapy were 55.6%, 55.6%, 100% and 0, 0, 0 respectively. The survival and local control rates of patients with reduced serum VEGF were significantly higher than those with stable serum VEGF (P<0.05). Multivariate analysis showed that the death risk of stage III patients raise obviously compared to stage Ⅰ patients(RR=4.868, P<0.05). Residual disease after radiotherapy is another death risk in esophageal cancer patients(RR=1.731, P<0.05). Conclusions Thalidomide may improve the prognosis of patients with locally advanced esophageal cancer who seserum VEGF level showed no change during radiotherapy, and its adverse reactions can be tolerated. Key words: Esophageal neoplasms; Radiotherapy; Thalidomide; Vascular endothelial growth factor; Prognosis

The safety and efficiency of photodynamic therapy for the treatment of osteosarcoma: A systematic review of in vitro experiment and animal model reports

Background Plantar warts are a common cutaneous disease of the sole of the foot caused by human papillomavirus. Photodynamic therapy has gained increasing attention in the treatment of plantar warts. Objective To investigate the effect of photodynamic therapy combined with transfer factor capsules in the treatment of multiple plantar warts. Methods Sixty-one patients with multiple plantar warts who visited our outpatient department from September 2017 to August 2019 were randomly divided into two groups. Twenty-three patients received photodynamic therapy (treatment group) and thirty-eight received cryotherapy (control group). Both groups also received immune modulator transfer factor capsules. Skin lesion score, numeric rating scale- (NRS-) 10 score, recurrence rate, adverse reactions, and Dermatology Life Quality Index (DLQI) were analyzed in both groups. Results The mean skin lesion score improved from 13.39 ± 3.88 before treatment to 1.48 ± 2.50 after the last treatment in the treatment group and from 12.47 ± 2.99 before treatment to 4.47 ± 3.67 after the last treatment in the control group. The success rate after 3 months of treatment was 86.96% in the treatment group and 39.47% in the control group. After 3 months of follow-up, the recurrence rate was significantly lower in the treatment group (20%) than in the control group (53.33%). The mean DLQI score at three months after treatment was significantly lower in the treatment group (3.61 ± 1.16) than in the control group (6.31 ± 2.59). Conclusion Photodynamic therapy combined with immunomodulators significantly increased the cure rate and reduced the recurrence rate of multiple plantar warts compared with traditional cryotherapy combined with immunomodulators.

Objective To explore the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on the proliferation and apoptosis of HaCaT cells stably expressing human papillomavirus type 16 E7 protein (HaCaT/HPVl6 E7 cells) . Methods Cultured HaCaT/HPV16 E7 cells were divided into several groups: blank control group receiving no treatment, ALA group treated with ALA alone, irradiation group irradiated with 630-nm red laser (30 mW/cm2, 12 J/cm2) , ALA-PDT groups pretreated with ALA for 5 hours followed by 630-nm red laser radiation at 4, 8, 12 J/cm2 respectively. CCK8 assay was performed to determine the survival rate of cells at 24 hours after PDT, and flow cytometry and confocal microscopy were conducted to detect cell apoptosis and observe cell morphology respectively at 3 hours. Results At 24 hours, the survival rate of cells was 68.98% ± 1.03%, 46.03% ± 2.96% and 23.57% ± 3.83% in the 4-, 8- and 12-J/cm2 ALA-PDT groups respectively, significantly lower than that in the blank control group, ALA group and irradiation group (99.15% ± 0.64%, 98.13% ± 0.83% and 96.85% ± 1.37% respectively, all P< 0. 05). With the increase in radiation dose, cell apoptosis was accelerated with obvious morphological changes and shrinkage of cells in the ALA-PDT groups. Conclusion ALA-PDT can inhibit the proliferation, and promote the apoptosis of HPV-infected HaCaT cells in a dose-dependent manner within a certain range of radiation dose. Key words: Aminolevulinic acid; Photochemotherapy; Cell proliferation; Apoptosis; Alphapapillomavirus; HPV16 E7

Purpose: to determine effectiveness of new technologies together with the methods included in the standards of treatment of malignant astrocytic tumors, by evaluating long-term results of integrated treatment of patients with malignant astrocityc tumors. Materials and methods: we have evaluated long-term results of treatment of 356 patients with malignant astrocytic supratentorial tumors (anaplastic astrocytomas, glioblastomas, giant cell glioblastomas, gliosarcomas). In addition to standard treatment (surgery, chemo- and radiotherapy) 37 patients had photodynamic therapy, 82 – specific antitumor immune therapy, 19 – both therapies. In 201 patients the structure of integrated treatment included only standard methods. A separate group was composed of 17 patients who had only stereotaxic biopsy as a stage of surgical treatment. Data obtained 6 months and later after surgery are referred to as long-term results. Results: photodynamic and specific antitumor immune therapy in patients with malignant supratentorial astrocytic tumors was safe and did not result in any adverse events increasing in comparison with control group. Better results were achieved in the group of patients who had photodynamic therapy. Photodynamic therapy application revealed to increase medium life expectancy (up to 50.79 and 47.86 months in patients with anapestic astrocitomas and glioblasomas respectively), and median survival (up to 35 months in patients with anaplastic astrocitomas and up to 30 months in patients with glioblastomas), as well as it decreases the risk of tumor recurrence. The use of photodynamic therapy together with specific antitumor immune therapy in addition to standard treatment methods did not reveal any significant advantages in comparison with photodynamic or standard treatment methods application only. Specific antitumor immune therapy based on autologous dendritic cells, also increases both medium life expectancy (anaplastic astrocytomas – 50.21 mths., glioblastomas – 23.72 mths.) and median survival (32 and 24 months respectively), when 3 courses and more are administered. 1 or 2 courses of immune therapy have no significant impact on medium life expectancy or median survival. Summary: development and clinical practice application of photodynamic therapy and specific antitumor immune therapy based on autologous dendritic cells is a perspective trend for future investigation and study, which will allow to improve long-term results of treatment of patients.

BACKGROUND Treatment of malignant gliomas is an extremely difficult objective associated with difficult choice of correct strategy. Photodynamic therapy is still not the treatment standard in these patients although this approach significantly improves treatment outcomes in surgery of gliomas. To demonstrate the possibilities of chlorin e6-mediated photodynamic therapy for malignant glial tumors. MATERIAL AND METHODS There were 161 patients with malignant supratentorial glial tumors who were treated at the Polenov Russian Neurosurgery Institute between 2009 and 2016. Eighty patients comprised the main group (photodynamic therapy), 81 ones — control group (without photodynamic therapy). RESULTS Photodynamic therapy in complex treatment of malignant brain gliomas significantly increases overall survival in patients with Grade III gliomas up to 39.1±5.5 months (control group — 22.8±3.3 months) and Grade IV gliomas up to 20.7±4.7 months (control group — 13.5±2.3 months) (p=0.0002). This method also increases relapse-free period in patients with Grade III gliomas up to 21.7±3.4 months (control group — 15.8±3.1 months) (p=0.0002) and Grade IV gliomas up to 11.1±2.1 months (control group — 8.0±2.3 months) (p=0.0001). CONCLUSION Considering our own and literature data, we can conclude that PDT in complex therapy of malignant gliomas improves long-term outcomes. This is partly achieved through higher resection quality due to inclusion of pathogenetic mechanisms of PDT affecting residual tumor cells. Therapeutic effect of PDT on tumor tissue differs significantly from the mechanisms of radio- and chemotherapy. Moreover, PDT does not complicate radio- and chemotherapy, but only potentiates the overall therapeutic effect. PDT has no systemic negative effects unlike adjuvant methods such as radio- and chemotherapy.