Hematoporphyrin derivative-mediated photodynamic techniques for the diagnosis and treatment of chordoma.

BACKGROUND: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. METHODS: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. RESULTS: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. CONCLUSION: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.

Photodynamic therapy for the treatment of port-wine stains in phakomatosis pigmentovascularis.

BACKGROUND: Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome. Only a few studies have reported the treatment of PPV, including a case using photodynamic therapy (PDT) to treat PPV-associated port-wine stains (PWS). OBJECTIVE: To investigating the efficacy and adverse effects of hemoporfin-PDT in PPV-associated PWS. METHODS: The efficacy and adverse effects in patients with PPV who underwent two sessions of hemoporfin-PDT from January 2019 to December 2022 were retrospectively analyzed. RESULTS: Twenty patients were included (13 females, 7 males, age range: 2-31 years; mean: 8.20 ± 8.92 years). Two, nine, seven, and two patients had PPV types Ia, IIa, IIb, and IIIa, respectively. After two treatments, the visual evaluation indicated the color of the PWS in 4, 5, 6, and 5 patients showed poor, fair, good, and excellent improvements, respectively. The combined good and excellent improvement rates in patients with PWS and pigmentary nevus overlapping in the same treatment area and in patients with PWS in the treatment areas only were 33.3% versus 87.5%, respectively, and were significantly different (p = 0.02). Minor side effects, such as edema, scabbing, hyperpigmentation, and blistering, were observed in some patients after PDT. CONCLUSION: Hemoporfin-PDT is an effective treatment for PPV-associated PWS. Patients with PWS and pigmentary nevus overlapping in the same treatment area showed poorer efficacy than patients with PWS in the treatment areas only.

Current clinical evidence is insufficient to support HMME-PDT as the first choice of treatment for young children with port wine birthmarks.

BACKGROUND: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades. AIM: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities. METHOD: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality. RESULT: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults. CONCLUSION: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy for acquired port-wine stain at lower extremity: Two case reports.

Two cases of acquired port-wine stain (APWS) at lower extremity were treated with hematoporphyrin monomethyl ether (HMME) and 532 nm LED green light-mediated photodynamic therapy (HMME-PDT). No serious adverse reactions were observed during or post-treatment period. Five-month follow-up showed significant reduction of red patches after a single HMME-PDT treatment in both cases.

Hematoporphyrin injection mediated photodynamic therapy for secondary squamous cell carcinoma of arsenical keratosis: A case report.

Hematoporphyrin injection (HpD) mediated photodynamic therapy (PDT) has demonstrated efficacy in treating various types of Bowen's disease, including basal-cell carcinoma, squamous cell carcinoma, extramammary Paget's disease, and actinic keratosis. We present a case of a male patient who developed squamous cell carcinoma as a result of repeated instances of arsenic-induced keratosis on both his hands and feet. Due to the involvement of the joint in both hands, the patient declined the conventional surgical resection treatment since it could potentially impact normal physiological function. Instead, the patient chose to undergo hemoporphyrin photodynamic therapy. After the treatment, the rash was entirely eliminated and there were no restrictions in the movement of the joint. Nevertheless, a local recurrence was detected throughout the two-year monitoring period. Arsenical keratosis carries a substantial likelihood of recurring. However, we believe that hemoporphyrin photodynamic therapy is effective in treating this condition.

Efficacy and influential factors of hematoporphyrin monomethyl ether mediated photodynamic therapy in the treatment for port-wine stains.

BACKGROUNDS: Hematoporphyrin monomethyl ether mediated photodynamic therapy (HMME-PDT) has emerged as an alternative approach for port-wine stain (PWS), which was primarily treated with pulsed dye laser (PDL). This study was aimed to evaluate the efficacy and safety of HMME-PDT for PWS and to explore influential factors on the efficacy. METHODS: A total of 254 patients were enrolled. Patients received an intravenous injection of HMME at 5 mg/kg. Lesion areas were irradiated with 532-nm light for 20-25 min. Efficacy was assessed according to fading of lesions and graded as excellent (≥90 %), good (60 %-89 %), fair (20 %-59 %), or poor (<20 %). Adverse events were recorded. Clinical data were analyzed including gender, age, lesion sub-type, lesion location and number of treatments. RESULTS: Overall, 72.4 % of patients achieved an effective response, with 27.6% showing excellent efficacy, 24.8 % showing good efficacy and 20.1 % showing fair efficacy. Only 27.6 % showed poor efficacy. Patients under the age of 18 obtained a better efficacy than adults. Lesions in face showed a better therapeutic outcome than those in neck or trunk and extremities. A more effective response was seen in pink type compared with nodular thickening type. Multiple HMME-PDT treatments could improve the clinical response. Lesion location, lesion sub-type, number of treatments were independent influential factors on efficacy. Adverse events included edema, blister, crust, hypopigmentation, hyperpigmentation, pain, itch and burning sensation. No severe systemic side events were observed. CONCLUSIONS: HMME-PDT was effective for treating PWS and was safe and well-tolerated by patients. It is worth further investigation in efficacy and safety involving more patients from medical institutions in different regions in China. The optimal treatment parameters and treatment protocols are still being explored in the clinical treatment for PWS.

Efficacy of hemoporfin-PDT on port-wine stains: A retrospective analysis of 2952 cases.

OBJECTIVE: To conduct a retrospective analysis of Hemoporfin photodynamic therapy (HMME-PDT) in the treatment of port-wine stains (PWS). METHOD: A retrospective analysis was conducted based on the clinical data from March 2017 to December 2022, so as to summarize the demographic characteristics, clinical efficacy and adverse reactions. The effectiveness of HMME-PDT was examined with respect to treatment times, age, gender, subtype, and location of PWS lesions. RESULT: The age of the 2952 cases ranged from 8 months to 56 years old (median, 2.8 years), with 1419 males (48.07 %), and 1533 females (51.93 %). There were 669 cases of pink type (22.66 %), 2184 cases of purplish red type (73.98 %), and 99 cases of nodular thickening type (3.35 %). The prevalence location was face (88.04 %), neck (14.94 %), limbs and trunk. 1602 cases (54.27 %) had never received treatment, 661 cases (22.39 %) had been treated by pulse dye laser (PDL), 229 cases (7.76 %) had previously been treated by PDT, 296 cases (10.03 %) had received both the modalities. The 2952 cases completed totally 7996 HMME-PDT times. Cure rate and effective rate increased continuously with the number of treatments. The pink type has the highest cure rate and effective rate, followed by the purplish red type and the last was the nodular thickening type. The therapeutic effects are considerably influenced by age, subtype, and treatment site (P < 0.05). However, there was no significant difference in the effectiveness of HMME-PDT between both genders. The local adverse reactions after the first treatment included edema (97.73 %), itching (82.62 %), purpura-like change (79.51 %), crusts (24.59 %), infection (4.07 %), scars (1.08 %), hyperpigmentation (0.61 %), and depigmentation (0.41 %). Nausea and vomiting occurred in 2 juveniles and 1 young adult (5, 6 and 22 years old respectively) immediately after treatment, and did not interfere with the administration of the treatment. Patients aged 21-30 were found to have a 3.4-fold higher likelihood of undergoing HMME-PDT under general anesthesia compared to those aged 15 or younger. There was no distinct systemic adverse reaction, such as allergic responses, cardiovascular effects, neurological symptoms, hematological abnormalities, respiratory symptoms, or musculoskeletal issues. CONCLUSION: HMME-PDT is preferred in treating PWS, with relatively high effective rate and cure rate, mild local reactions and no distinct systemic adverse reaction.

Case report: Hematoporphyrin injection (HpD) photodynamic therapy for the treatment of groin extramammary Paget's disease in an elderly male patient.

Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) is a modality for cancer treatment, particularly suitable for challenging sites or elderly patients who can benefit from its minimally invasive and selective nature. We report a case of groin extramammary Paget's disease (EMPD) in a male patient with a lesion located in the right mons pubis. The patient was deemed unsuitable for surgical treatment due to his advanced age, underlying health conditions, extensive rash area, and the specific location of the groin lesion. He opted for hematoporphyrin photodynamic therapy instead of traditional wide local excision. The tumors were successfully treated, with no recurrence observed during the follow-up period. We suggest that hematoporphyrin photodynamic therapy may be an effective alternative to conventional surgery for the treatment of extramammary Paget's disease.

Influential Factors in the Efficacy of Hemoporfin-Mediated Photodynamic Therapy for Port-wine Stains.

Hemoporfin-mediated photodynamic therapy (HMME-PDT) is commonly used in the treatment of port-wine stains (PWS). However, the influential factors for the efficacy of the treatment are not well defined. This study intends to observe the influential factors for the efficacy of HMME-PDT in the treatment of port-wine stains (PWS). A total of 551 patients with PWS of head and neck was enrolled in this retrospective study. Further screening the patients of facial PWS, 484 patients were chosen. Patients were treated with HMME-PDT. All patients received 1~3 sessions of treatment with 2~3-month intervals. We photographed the lesions before each session and 2~3 months after the last session. Ages, sessions, lesion subtypes, and previous treatment history were related to the response of HMME-PDT (P =0.032, P<0.001, P=0.012, P=0.003 respectively). Treatment sessions were the independent factor correlated with efficacy after 3 sessions of treatment. Patients with no treatment history targeting PWS showed higher efficacy than those were treated with laser or other photodynamic treatment (P<0.05). The efficacy was higher by increasing the sessions of treatment. The efficacy was higher for lesion on maxillary prominence area and mandibular prominence area that on frontonasal prominence area and optic vesicle area (P<0.05). HMME-PDT is an effective in the treatment of PWS. Patients received no previous treatment for PWS, total treatment sessions and lesion on maxillary prominence area and mandibular prominence area are positive factors.

Efficacy of hematoporphyrin injection (HpD) photodynamic therapy in the treatment of widespread extramammary Paget's disease.

Photodynamic therapy (PDT) utilizing Hematoporphyrin Derivative (HpD) injection has been demonstrated as an efficacious treatment for various conditions, including Bowen's disease, subtypes of basal cell carcinomas, and actinic keratosis. While surgical resection is considered the primary treatment option for extramammary Paget's disease (EMPD), some patients may not be suitable candidates for surgical intervention. ALA-PDT may have some benefits in treating EMPD in select patients, while Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) has demonstrated promising potential as a cancer treatment. We present one case of vulvar extramammary Paget's disease (EMPD), that is a female patient with lesions in the vulva and involving the urethra. Due to advanced age, underlying diseases, the extensive affected area, and the specific location of the vulvar lesion, the patients were unable to undergo surgical treatment. Therefore, the patient declined traditional wide local excision and instead opted for hematoporphyrin photodynamic therapy. Treatment eliminated the tumor, but it recurred locally after 1.5 years of follow-up. Localized small-scale recurrence at the affected site can be treated with surgical resection or photodynamic therapy to achieve complete clearance of the lesion. However, the patient refuses further examination and treatment. EMPD has a high recurrence rate, but we propose that hematoporphyrin photodynamic therapy is an effective alternative to conventional surgery for treating this condition, even in case of recurrence.

Study of hematoporphyrin monomethyl ether-mediated blue-light photodynamic therapy in the treatment of oral ulcers infected with Staphylococcus aureus: In vivo evaluation.

Clinical suppurative infection is mainly caused by Staphylococcus aureus. Although many antibiotics can be used to kill S. aureus, the resulting resistance problem is difficult to solve. Therefore, it is necessary to seek a new sterilizing method to solve the problem of drug resistance of S. aureus and improve the therapeutic effect of infectious diseases. Photodynamic therapy (PDT) has become an alternative for the treatment of a variety of drug-resistant infectious diseases due to its advantages of non-invasive, specific targeting, and no drug resistance. We have confirmed the advantages and experimental parameters of blue-light PDT sterilization in vitro experiments. This study aimed to treat buccal mucosa ulcer of hamster infected with S. aureus according to the parameters obtained in vitro experiment, and observe the bactericidal effect of hematoporphyrin monomethyl ether (HMME) mediated blue-light PDT in vivo and its therapeutic effect on tissue infection. The results indicated that HMME mediated blue-light PDT can effectively kill S. aureus in vivo and promote the healing of the oral infectious wound.The study findings lay a foundation for carrying out more HMME mediated blue-light PDT sterilizing therapy.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy for phakomatosis pigmentovascularis type â ¡: A case report.

Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome characterized by capillary malformation (mainly port-wine stains, PWS) and pigmentary nevi with or without extracutaneous signs. Efforts are ongoing to develop laser therapy to treat vascular and pigmentation abnormalities in PPV. The status of pulsed-dye lasers in the treatment of PWS has been challenged by vascular-targeted photodynamic therapy (PDT). Hematoporphyrin monomethyl ether-mediated PDT (HMME-PDT) has become a research hotspot for PWS. The long-term efficiency and safety of HMME-PDT for vascular lesions coexisting with pigmented lesions in PPV have not been reported. We report a pediatric case of PPV type Ⅱa presenting with PWS and nevus of Ota efficiently treated through a 3-session HMME-PDT. After treatment, the PWS lesions regressed significantly without noticeable adverse reactions or recurrence. Besides, we share the dermoscopy data of PPV lesions and discuss the clinical manifestations and therapeutic strategies for PPV based on existing related literature.

Co-delivery of gefitinib and hematoporphyrin by aptamer-modified fluorinated dendrimer for hypoxia alleviation and enhanced synergistic chemo-photodynamic therapy of NSCLC.

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-based molecular targeted therapy are proved to be effective in the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation, its efficacy is limited by the acquired drug resistance. The combination of EGFR-TKIs with photodynamic therapy (PDT) has been explored to combat NSCLC with promising synergistic results. However, hypoxic tumor microenvironment is associated with the development of EGFR-TKIs resistance and severely limits the efficacy of PDT. Here, we synthesized an aptamer modified fluorinated dendrimer (APF) as a drug carrier and prepared nanocomplexes APFHG by encapsulation of gefitinib (Gef) and hematoporphyrin (Hp). APF has good oxygen-carrying capacity, high drug entrapment efficiency, and could release Gef and Hp in response to intracellular pH. APF can specifically recognize EGFR-positive NSCLC cells and effectively improve the tumor hypoxic microenvironment due to the targeting effect of aptamer and the good oxygen-carrying capacity of the fluorinated dendrimer. Under the laser irradiation, APFHG can significantly increase the production of the intracellular reactive oxygen species and produce a synergistic therapeutic effect in inhibition of cellular growth and induction of cell cycle arrest and apoptosis on both Gef-sensitive and Gef-resistant EGFR-mutant NSCLC cells through PDT/molecular targeted therapy. This work indicates that fluorinated dendrimer could be a potent drug delivery platform to overcome hypoxia-related resistance and the co-delivery of EGFR-TKI and photosensitizer by the fluorinated dendrimer could be a promising therapeutic approach for reversal of EGFR-TKIs resistance in EGFR mutation-positive NSCLC.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy temporarily relieves severe pruritis from phakomatosis pigmentovascularis: A case report.

Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome characterized by (a) capillary malformations, such as port-wine stain (PWS), and (b) pigmented lesions, such as pigmented trichoepidermal nevus, café-au-lait spots, and dermal melanocytosis with or without systemic damage. Severe pruritus has not previously been reported among PPV patients. Here, we report a pediatric case of PPV with severe pruritus, which was refractory to various long-term oral antiallergic agents and topical tacrolimus but was temporarily responsive to hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT). HMME-PDT is the latest technology used in treating PWS following the basic principle of targeted photodynamic destruction of the vascular wall of the lesion. Furthermore, many studies have confirmed the safety and efficacy of HMME-PDT for PWS in both adults and children. Specific pathophysiologic mechanisms and treatment methods must be further explored to advance our understanding of the disease and improve the quality of life in PPV patients.

Synthesis and evaluation of novel fluorinated hematoporphyrin ether derivatives for photodynamic therapy.

A photosensitizer with high phototoxicity, suitable amphipathy and low dark toxicity could play a pivotal role in photodynamic therapy (PDT). In this study, a facile and versatile approach was adopted to synthesize a series of novel fluorinated hematoporphyrin ether derivatives (I1-I5 and II1-II4), and the photodynamic activities of these compounds were studied. Compared to hematoporphyrin monomethyl ether (HMME), all PSs showed preferable photodynamic activity against A549 lung tumor cells. The longest visible absorption wavelength of these compounds was approximately 622 nm. Among them, II3 revealed the highest singlet oxygen yield (0.0957 min-1), the strongest phototoxicity (IC50 = 1.24 µM), the lowest dark toxicity in vitro, and exhibited excellent anti-tumor effects in vivo. So compound II3 could act as new drug candidate for photodynamic therapy.

Successful treatment of facial hypertrophic scar with HMME-PDT: A case report.

Treating hypertrophic scars is a challenge for clinicians. Herein, we report a case of one female with both a facial port wine stain and a hypertrophic scar treated with Hematoporphyrin monomethyl ether photodynamic therapy. Surprisingly, with the treatment of the facial port wine stain, the other skin lesion, the hypertrophic scar, also alleviated. HMME-PDT has been approved for application in PWS; however, this case showed effective easing of the hypertrophic scar lesion, which indicates that it might be a promising therapeutic method for hypertrophic scars.

Clinical Efficacy of HiPorfin Photodynamic Therapy for Advanced Obstructive Esophageal Cancer.

OBJECTIVE: To explore the clinical efficacy of HiPorfin photodynamic therapy for advanced esophageal cancer and evaluate its impact on survival. METHODS: Retrospective analysis of 32 patients with advanced obstructive esophageal cancer at our institution from September 2013 to December 2016. HiPorfin was infused as the photosensitizer at a dose of 5 mg/kg, and after 48 hours, 630-nm laser irradiation was subsequently performed through an optical fiber that passed through the biopsy channel of a flexible endoscope. RESULTS: The effectiveness rate was 78.1% (25/32), and the significant efficacy rate was 56.3% (18/32). The dysphagia score decreased from 3.43 ± 0.73 to 1.79 ± 0.53 (P < .05). There was no grade 3 or more toxicity. The median overall survival was estimated to be 16 months. Univariate analysis showed higher overall survival with a Karnofsky Performance Status score ≥80 compared with a Karnofsky Performance Status score <80 (hazard ratio: 2.626; 95% CI: 1.091-6.322; P = .024). Overall survival was higher in patients who had received radiation therapy than in patients who did not receive radiation therapy (hazard ratio: 3.574; 95% CI: 1.501-8.510; P = .002). CONCLUSION: Photodynamic therapy is an effective method for advanced esophageal cancer. The side effects are mild, and the short-term effect is good, especially in the relief of dysphagia. Photodynamic therapy can prolong the survival of patients with advanced esophageal cancer, and the Karnofsky Performance Status score and previous radiation therapy have a significant effect on the overall survival.

Photodynamic therapy for port-wine stains in extremities: Report of 4 cases.

OBJECTIVES: To observe the clinical efficacy of photodynamic therapy mediated by hemoporfin (HMME-PDT) for port-wine stains (PWS) on extremities and explore its possible influencing factors. METHODS: Four patients with PWS in extremities were treated by HMME-PDT, and patients with negative results in the skin test were given an intravenous injection of 5 mg/kg of HMME. The patients were irradiated with 532 nm LED green light, and immediately applied cold compress after treatment. These patients were informed to stay away from light for two weeks. A follow-up every 2 weeks was conducted with treatment for 2 or 3 times in total. After the end of treatment, a follow-up was carried out for 6-12 months and the efficacy and safety were evaluated. RESULT: Three of the four patients were considered cured, and the treatment was ineffective for one patient. During the follow-up observation, all patients had different degrees of edema, and there were no signs of chromatosis or scarring. CONCLUSION: PDT treatment for patients with extremity PWS demonstrate high efficiency and safety, without obvious adverse reactions and recurrence.