Pharmaceutical equivalent 5-aminolevulinic acid fluorescence guided resection of central nervous system tumors: feasibility, safeness and cost-benefit considerations.

PURPOSE: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) has been an essential tool in the 'standard of care' of malignant gliomas. Over the last two decades, its indications have been extended to other neoplasms, such as metastases and meningiomas. However, its availability and cost-benefit still pose a challenge for widespread use. The present article reports a retrospective series of 707 cases of central nervous system (CNS) tumors submitted to FGR with pharmacological equivalent 5-ALA and discusses financial implications, feasibility and safeness. METHODS: From December 2015 to February 2024, a retrospective single institution series of 707 cases of 5-ALA FGR were analyzed. Age, gender, 5-ALA dosage, intraoperative fluorescence finding, diagnosis and adverse effects were recorded. Financial impact in the surgical treatment cost were also reported. RESULTS: there was an additional cost estimated in $300 dollars for each case, increasing from 2,37 to 3,28% of the total hospitalization cost. There were 19 (2,69%) cases of asymptomatic photosensitive reaction and 2 (0,28%) cases of photosensitive reaction requiring symptomatic treatment. 1 (0,14%) patient had a cutaneous rash sustained for up to 10 days. No other complications related to the method were evident. In 3 (0,42%) cases of patients with intracranial hypertension, there was vomiting after administration. CONCLUSION: FGR with pharmacological equivalent 5-ALA can be considered safe and efficient and incorporates a small increase in hospital expenses. It constitutes a reliable solution in avoiding prohibitive costs worldwide, especially in countries where commercial 5-ALA is unavailable.

In vitro modeling of recurrent Dermatofibrosarcoma Protuberans: Assessment of 5-aminolevulinic acid photodynamic therapy efficacy.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

Comparative assessment of disease recurrence after transurethral resection of non-muscle-invasive bladder cancer with and without a photodynamic diagnosis using 5-aminolevulinic acid: a propensity score-matching analysis.

BACKGROUND: Among patients with non-muscle-invasive bladder cancer (NMIBC), systematic reviews showed lower recurrence rate in patients treated with photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) than with white-light (WL) TURBT. However, the result is not consistent between clinical trials and the significance of preoperatively available factors in disease recurrence after PDD-TURBT remains unclear. METHODS: The present study retrospectively analyzed 1174 NMIBC patients who underwent TURBT and were followed up for ≥ 6 months. Among 1174 patients, 385 and 789 underwent PDD-TURBT with oral 5-aminolevulinic acid (the PDD group) and WL-TURBT (the WL group), respectively. Recurrence-free survival (RFS) was compared between the PDD and WL groups before and after propensity score matching, and the impact of several baseline parameters on RFS between the 2 groups was investigated after matching. RESULTS: Before propensity score matching, RFS was significantly longer in the PDD group than in the WL group (P = 0.006). After matching, 383 patients were included in both groups, and RFS was significantly longer in the PDD group than in the WL group (P < 0.001). In the cohort after matching, RFS between the two groups was compared in each subgroup classified according to baseline parameters, including age, sex, history of previous or concomitant upper urinary tract urothelial carcinoma, preoperative urinary cytology, tumor multiplicity, and tumor size, and significantly longer RFS was observed in the PDD group in all subgroups, except for the patients with tumors ≥ 30 mm (P = 0.21). CONCLUSION: These results suggest that PDD-TURBT prolongs RFS in NMIBC patients, except for those with tumors ≥ 30 mm.

Dosagem de porfobilinogênio urinário para confirmação diagnóstica ou prognóstico de porfirias hepáticas agudas / Dosage of urinary porphobilinogen for diagnostic confirmation or prognosis of acute hepatic porphyrias

INTRODUÇÃO: As porfirias são distúrbios metabólicos raros hereditários ou adquiridos em que há uma deficiência parcial ou completa em uma das oito enzimas da via de biossíntese do heme, que é grupo prostético que consiste de um átomo de ferro contido no centro de um largo anel orgânico heterocíclico. Esse grupo tem importância biológica por ser grupo prostético de proteínas, conhecidas como hemeproteínas. Com base no tecido afetado, as porfirias podem ser classificadas como eritropoiéticas ou hepáticas e, com base na apresentação dos sintomas, podem ser classificadas como porfirias hepáticas agudas (PHA) ou cutâneas. Os testes de primeira linha recomendados para diagnóstico da PHA incluem dosagem de PBG (dPBG; análise quantitativa), ácido delta-aminolevulinico (ALA) e porfirinas em uma amostra de urina aleatória. Atualmente, há disponível no SUS apenas o procedimento para a realização da pesquisa de PBG urinário (pPBGu; análise qualitativa). Tendo em vista a recorrência de falso-positivos ou falso-negativos provenientes da pPBGu urinário, foram analisadas as evidências científicas dis

Assessment of therapeutic efficacy in seven cases of basal cell carcinoma in the ear and nose region treated with new surgical excision and immediate photodynamic therapy.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent non-melanoma skin tumor. It commonly affects exposed areas. Currently, surgical resection is considered the primary approach for BCC treatment. However, BCC frequently affects exposed facial areas, leading to visible scars after surgery. PDT has garnered increasing recent attention, demonstrating superior efficacy and favorable cosmetic outcomes for superficial BCCs. However, it shows limited treatment effectiveness for deep-seated tumors. Most of the current literature focuses on the combination of surgery and postoperative PDT, while no studies have reported on the use of standard surgical excision with intraoperative margin pathological monitoring and immediate PDT. Therefore, we implemented a treatment protocol combining surgery and immediate PDT. Accordingly, this paper aimed to explore the effectiveness, cosmetic outcomes, and other relevant advantages of this therapeutic approach. METHODS: We aimed to evaluate this approach in seven patients with BCC on the nose and ears. Standard surgical excision of skin lesions was performed, with intraoperative frozen section examination of the margins, followed by immediate postoperative PDT for the wounds, and continued periodic PDT during the second phase of wound healing. RESULTS: All seven cases demonstrated significant improvement. The cosmetic rating was 100 % and no cases of recurrence existed among the seven patients. CONCLUSIONS: This approach effectively minimized the surgical wound, improved tumor clearance, achieved precise therapeutic effects, and reduced the recurrence rate. Moreover, it produced favorable cosmetic outcomes.

A cost-consequences and budget impact analysis of blue light-guided cystoscopy with Hexvix in patients diagnosed with non-muscle-invasive bladder cancer in France.

AIMS: French guidelines for the management of non-muscle-invasive bladder cancer recommend that blue-light cystoscopy should be used in patients where the risk of missing residual tumor is highest. Despite evidence for its cost-effectiveness, budgetary concerns have limited uptake in France. The aim of this analysis was to model the cost-consequences of adopting the recommendations in a French urology unit. MATERIALS AND METHODS: A budget impact model was developed in Excel, using a decision tree approach derived from guidelines issued by L'Academie franÒ«aise d'urologie. Risk profiles were derived from an analysis of studies using white-light cystoscopy; estimates for the impact of blue-light cystoscopy were derived from a published Cochrane Review. Costs were based on published tariff prices from L'Agence Technique de L'Information sur L'Hospitalisation. The model allowed results to be tailored to activity levels and projected blue-light usage in the chosen urology unit. RESULTS: Two scenarios were evaluated, based on a 3-year time horizon. Full implementation of all recommendations within a large public hospital was estimated to yield incremental costs of €269 per procedure (∼10% increase overall); a more targeted approach within a smaller private hospital yielded incremental costs of €133 per procedure (5% increase overall). LIMITATIONS: The basis of the model is a change in the time to first recurrence. There are no data available for subsequent recurrences or progression, both of which could have an influence on expenditure. Secondly, recurrence rates for blue-light cystoscopy were not specifically available for each patient group identified in the guidelines: extrapolation of data may have resulted in bias. Finally, the data were derived from clinical trials, which may not be generalisable to real-world clinical practice. CONCLUSIONS: The model has shown that the additional expenditure required to implement blue-light cystoscopy is modest and not disproportionate to the overall cost of care.

Real-world experience with 5-aminolevulinic acid for photodynamic diagnosis of bladder cancer (3rd report): Cost impact of transurethral resection of bladder tumor in Japan.

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) showed improvement of diagnostic accuracy and treatment efficacy compared to white light TURBT (WL-TURBT). While PDD-TURBT is highly effective, PDD-TURBT requires the use of PDD device and light-sensitive substance precursor, which increases the medical cost compared to WL-TURBT. In this study, the impact on health care economic costs were examined between PDD-TURBT and WL-TURBT. METHODS: Of the total 265 patients, 88 patients for WL-TURBT and 105 patients for PDD-TURBT were available for analysis. Costs were also examined between 34 patients without false-positives and 36 patients with false-positives with a follow-up period of at least 200 days. To compare costs between the two treatments, we calculated the cost/person/year of TURBT using Japanese Diagnosis Procedure Combination and Per-Diem Payment System (DPC/PDPS). RESULTS: The total number of surgeries including the first TURBT was 135 (47 recurrences) in the WL-TURBT group and 133 (28 recurrences) in the PDD-TURBT group. The cost per person for hospitalization and surgery was 366,310 Japanese yen (JPY) for the WL-TURBT and 501,930 JPY for the PDD-TURBT. The cost per person per year was 491,622 JPY in the WL-TURBT group and 506,405 JPY in the PDD-TURBT group. Regarding false-positives, the cost per person per year was 494,544 JPY in the group without false-positives and 328,086 JPY in the group with false-positives. CONCLUSIONS: Although PDD-TURBT is cost more than WL-TURBT for one surgical hospitalization, the cost per person per year for PDD-TURBT and WL-TURBT is cost-neutral.

Clinical assessment of a low-cost, hand-held, smartphone-attached intraoral imaging probe for 5-aminolevulinic acid photodynamic therapy monitoring and guidance.

Significance: India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed. Aim: Our study aimed to use a hand-held smartphone-coupled intraoral imaging device, previously investigated for autofluorescence (auto-FL) diagnostics adapted here for treatment guidance and monitoring photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence (FL). Approach: A total of 12 patients with 14 buccal mucosal lesions having moderately/well-differentiated micro-invasive OSCC lesions (<2 cm diameter and <5 mm depth) were systemically (in oral solution) administered three doses of 20 mg/kg ALA (total 60 mg/kg). Lesion site PpIX and auto-FL were imaged using the multichannel FL and polarized white-light oral cancer imaging probe before/after ALA administration and after light delivery (fractionated, total 100 J/cm2 of 635 nm red LED light). Results: The handheld device was conducive for access to lesion site images in the oral cavity. Segmentation of ratiometric images in which PpIX FL is mapped relative to auto-FL enabled improved demarcation of lesion boundaries relative to PpIX alone. A relative FL (R-value) threshold of 1.4 was found to segment lesion site PpIX production among the patients with mild to severe dysplasia malignancy. The segmented lesion size is well correlated with ultrasound findings. Lesions for which R-value was >1.65 at the time of treatment were associated with successful outcomes. Conclusion: These results indicate the utility of a low-cost, handheld intraoral imaging probe for image-guided PDT and treatment monitoring while also laying the groundwork for an integrated approach, combining cancer screening and treatment with the same hardware.

High-frequency ultrasound assessment of vulvar lichen sclerosus treated with photodynamic therapy.

BACKGROUND: Patients with vulvar lichen sclerosus (VLS) are faced with a decreased quality of life and an increased risk of vulvar malignancy. 5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) can serve as an alternative for refractory VLS patients. However, high-frequency ultrasound (HFUS) has never been introduced in the ALA-PDT outcome assessment for VLS patients. METHODS: A prospective study was conducted. Refractory VLS patients received two treatment courses of ALA-PDT (3 times of remedies at 2-week intervals for each course), and underwent clinical, HFUS and histopathological assessment. Statistical analysis comparing parameters at baseline and after ALA-PDT was performed. RESULTS: Thirty-one VLS patients were included. Both subjective symptoms (itch and burning pain) and objective severity (lesion size and hypopigmentation) were relieved significantly after ALA-PDT treatment. Hypoechoic dermal band (HDB) thickness revealed by HFUS decreased progressively with successive ALA-PDT treatment, and the reduction value had a positive correlation with the reduction of inflammatory infiltration depth in histopathology. Collagen homogenization depth decrease was also noticed. Besides, adverse effects were recorded, mainly as mild and transient post-treatment edema and pain. CONCLUSIONS: ALA-PDT is an effective and safe therapeutic option for refractory VLS patients. HFUS can act as a complement to the non-invasive treatment monitoring for its objectivity, quantifiability and precision in the distinct vertical perspective.

Clinical and economic impact of blue light cystoscopy in the management of NMIBC at US ambulatory surgical centers: what is the site-of-service disparity?

INTRODUCTION AND OBJECTIVE: Management of non-muscle-invasive bladder cancer (NMIBC) significantly impacts healthcare resource utilization due to requirements for ongoing surveillance. White light cystoscopy (WLC) represents the traditional approach to NMIBC disease surveillance, though physicians utilizing WLC alone may fail to detect all cancerous lesions. The approval of blue light cystoscopy (BLC) as an adjunct to WLC enhances the urologist's ability to more readily detect cancerous tissue. A more complete resection will reduce recurrences and could result in reduced costs for the US healthcare system. This analysis quantifies the clinical and economic impact of the incorporation of BLC in the management of NMIBC in ambulatory surgical centers (ASCs) considering current Center for Medicare Services (CMS) patient-physician coverage and reimbursement. METHODS AND MATERIALS: A budget impact model was developed to assess projected ASC costs for a cohort of 50 newly diagnosed bladder cancer patients over a 2-year follow-up comparing WLC alone vs. WLC + BLC. Treatment and surveillance intervals were based on AUA/SUO clinical guidelines. Clinical and cost metrics for staging and biopsy rates were assessed, with cost inputs based on Medicare reimbursement rates. RESULTS: Use of WLC + BLC for NMIBC surveillance resulted in the identification of 5 additional NMIBC recurrences compared to WLC alone. There was an associated increased cost of performing BLC in an ASC setting, with a net increase in the total cost of care for NMIBC of $110 per cystoscopy over a 2-year period. If recurrences missed using WLC alone were to progress prior to detection, the model projects an increase in treatment costs borne by Medicare of $9,097 to $34,538 due to more intensive treatments required for the increased risk of recurrence. CONCLUSIONS: Modeled results suggests that the Medicare program will incur increased costs, due to the gap between added costs per cystoscopy due to BLC. The current discrepancy in reimbursement disincentivizes community-based ASCs from adopting BLC, resulting in suboptimal patient care while increasing downstream treatment costs to Medicare, necessitated when missed disease progresses to higher stage/grade disease. The findings have important clinical implications for the optimal management of NMIBC and should inform healthcare policies that promote cost-effectiveness and enhanced patient outcomes.

Assessment of reflectance confocal microscopy for monitoring treatment of actinic keratosis and field cancerization with daylight photodynamic therapy.

Actinic keratosis (AK) is the most common pre-malignant cutaneous lesion of the skin, often associated with field cancerization. Daylight photodynamic therapy (DL-PDT) is used as treatment, showing good histological results. Reflectance confocal microscopy (RCM) may be useful as a non-invasive, real-time approach to monitor treatment, however, there is a lack of data on the correlation between RCM and histopathological findings in AK patients treated with DL-PDT. To correlate histological and RCM findings and evaluate the efficacy of DL-PDT in patients with AK and field cancerization treated with DL-PDT. Patients with field cancerization and a minimum of six AK lesions on the face were included in the study. A single session combining methyl aminolevulinate followed by two-hour daylight exposure of the face was performed. RCM and biopsy were performed before and after three months of the intervention to compare efficacy between patients using the Wilcoxon test, and concordance of the findings based on the different methods was analysed using the Kappa test. Twenty-four patients completed the study. An improvement in photodamage and a decrease in the number of AK lesions (45.3% reduction) was observed. Regression in atypia and dysplasia was observed via histopathology and RCM, however, there was poor agreement between the methods. No changes were observed after treatment for inflammation, fibroplasia and acantholysis. Concordance between histological and RCM findings was poor, suggesting that RCM cannot replace the histopathological examination, however, it may be used as an adjuvant test for follow-up of patients. Despite this, DL-PDT proved to be an effective method for treating AK.

Clinical evaluation of a mobile, low-cost system for fluorescence guided photodynamic therapy of early oral cancer in India.

BACKGROUND: Morbidity and mortality due to oral cancer in India are exacerbated by a lack of access to effective treatments amongst medically underserved populations. We developed a user-friendly low-cost, portable fibre-coupled LED system for photodynamic therapy (PDT) of early oral lesions, using a smartphone fluorescence imaging device for treatment guidance, and 3D printed fibreoptic attachments for ergonomic intraoral light delivery. METHODS: 30 patients with T1N0M0 buccal mucosal cancer were recruited from the JN Medical College clinics, Aligarh, and rural screening camps. Tumour limits were defined by external ultrasound (US), white light photos and increased tumour fluorescence after oral administration of the photosensitising agent ALA (60 mg/kg, divided doses), monitored by a smartphone fluorescence imaging device. 100 J/cm2 LED light (635 nm peak) was delivered followed by repeat fluorescence to assess photobleaching. US and biopsy were repeated after 7-17 days. This trial is registered with ClinicalTrials.gov, NCT03638622, and the study has been completed. FINDINGS: There were no significant complications or discomfort. No sedation was required. No residual disease was detected in 22 out of 30 patients who completed the study (26 of 34 lesions, 76% complete tumour response, 50 weeks median follow-up) with up to 7.2 mm depth of necrosis. Treatment failures were attributed to large tumour size and/or inadequate light delivery (documented by limited photobleaching). Moderately differentiated lesions were more responsive than well-differentiated cancers. INTERPRETATION: This simple and low-cost adaptation of fluorescenceguided PDT is effective for treatment of early-stage malignant oral lesions and may have implications in global health.

First in patient assessment of brain tumor infiltrative margins using simultaneous time-resolved measurements of 5-ALA-induced PpIX fluorescence and tissue autofluorescence.

SIGNIFICANCE: 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is currently used for image-guided glioma resection. Typically, this widefield imaging method highlights the bulk of high-grade gliomas, but it underperforms at the infiltrating edge where PpIX fluorescence is not visible to the eyes. Fluorescence lifetime imaging (FLIm) has the potential to detect PpIX fluorescence below the visible detection threshold. Moreover, simultaneous acquisition of time-resolved nicotinamide adenine (phosphate) dinucleotide [NAD(P)H] fluorescence may provide metabolic information from the tumor environment to further improve overall tumor detection. AIM: We investigate the ability of pulse sampling, fiber-based FLIm to simultaneously image PpIX and NAD(P)H fluorescence of glioma infiltrative margins in patients. APPROACH: A mesoscopic fiber-based point-scanning FLIm device (355 nm pulses) was used to simultaneously resolve the fluorescence decay of PpIX (629/53 nm) and NAD(P)H (470/28 nm). The FLIm device enabled data acquisition at room light and rapid (<33 ms) augmentation of FLIm parameters on the surgical field-of-view. FLIm measurements from superficial tumors and tissue areas around the resection margins were performed on three glioblastoma patients in vivo following inspection of PpIX visible fluorescence with a conventional neurosurgical microscope. Microbiopsies were collected from FLIm imaged areas for histopathological evaluation. RESULTS: The average lifetime from PpIX and NAD(P)H fluorescence distinguished between tumor and surrounding tissue. FLIm measurements of resection margins presented a range of PpIX and NAD(P)H lifetime values (τPpIX   ∼ 3 to 14 ns, τNAD(P)H = 3 to 6 ns) associated with unaffected tissue and areas of low-density tumor infiltration. CONCLUSIONS: Intraoperative FLIm could simultaneously detect the emission of PpIX and NAD(P)H from patients in vivo during craniotomy procedures. This approach doubles as a clinical tool to identify tumor areas while performing tissue resection and as a research tool to study tumor microenvironmental changes in vivo. Intraoperative FLIm of 5-ALA-induced PpIX and tissue autofluorescence makes a promising surgical adjunct to guide tumor resection surgery.

Frameless Stereotactic Biopsy with Intraoperative Computed Tomography "Assessment of Efficacy and Real Target Registration Error".

Frameless stereotactic brain biopsy (FSB) with navigation system has been widely used. We reported preliminary experience of FSB with intraoperative computed tomography (iCT) and examined the usefulness of this novel adjuvant technique and real target registration error (rTRE) of FSB. The FSB with 5-aminolevulinic acid (5-ALA) and iCT was performed on 10 patients. The gadolinium-enhanced lesions on magnetic resonance image were defined as the biopsy target. In the procedure, iCTs were scanned twice, for autoregistration of the navigation system and for confirmation of the position of the actual inserted biopsy needle. The red fluorescence of the samples was observed under excitation with violet-blue light through a low-cut filter of neurosurgical microscope. The distance between the planned target and the tip of the biopsy needle in the image of iCT was calculated in a workstation for the assessment of rTRE. The median volume of the target was 12.13 mL (0.06-39.15 mL). We performed the surgical procedure in a prone position in four patients. None to faint 5-ALA-induced fluorescence was observed in six samples. There existed no sampling errors. The mean target distance between the planned and real targets of the mean rTRE of FSB was 2.7 ± 0.56 mm. The real TRE of FSB was first reported and was larger than the reported rTRE exactly calculated from the fiducial registration error. iCT guarantees accurate tumor sampling with autoregistration regardless of the surgical position and prevents inaccurate biopsy to occur even with ALA fluorescence assistance.

Macro and microeconomics of blue light cystoscopy with CYSVIEW® in non-muscle invasive bladder cancer.

OBJECTIVE: To determine the estimated budget impact to practices that incorporate blue light cystoscopy (BLC) with hexaminolevulinate HCl (HAL) for the surveillance of non-muscle-invasive bladder cancer (NMIBC) in the clinic setting. With the introduction of advanced technologies in the clinic setting such as HAL, further cost comparative research is needed to justify HAL as a high value option. MATERIAL AND METHODS: A budget impact model was developed from the facility perspective assessing projected costs at 2 years for a simulated facility with 50 newly diagnosed bladder cancer patients. Treatment and surveillance cystoscopy intervals were based on clinical guidelines. Clinical inputs, including tumor stage and grade at diagnosis, rates of recurrence and relative risk reduction when using BLC with HAL, were derived from published studies. Cost inputs were based on Medicare reimbursement rates and facility costs. RESULTS: Use of BLC identified 9 additional recurrences over two years compared to white light cystoscopy alone. Use of flexible BLC for surveillance marginally increased costs to the practice, with a net difference of $0.76 per cystoscopy over 2 years. CONCLUSIONS: From the office/clinic perspective, the model suggests that the use of flexible BLC for the surveillance of NMIBC may not impact cost per cystoscopy and identifies 9 recurrences over 2 years that would be missed using white light cystoscopy alone. These findings could have important implications in the management of NIMBC and help guide clinical practice guidelines that promote cost-effective care and improved patient outcomes.

A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Recurrence of non­muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection. METHODS: In this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)­guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat. RESULTS: A total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months' median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444). CONCLUSIONS: PDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

In Vivo Assessment of Mitochondrial Oxygen Consumption.

The Protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT) has been proposed by us as a potential clinical noninvasive tool for monitoring mitochondrial function. We have been working on the development of mitochondrial respirometry for monitoring mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in skin. In this work, we describe the principles of the method in small experimental animals.

Avaliação da redução da carga viral do papilomavírus humano por meio da captura híbrida após terapia fotodinâmica em lesões intraepiteliais cervicais alto grau / Load reduction assessment human papillomavirus viral through hybrid capture after photodynamic therapy in injuries high grade cervical intraepithelial

Contexto e objetivo: No mundo, aproximadamente 20 milhões de mulheres encontram-se infectadas pelo papilomavírus humano (HPV). Esta infecção pode ser assintomática ou causar papilomas verrucosos benignos, neoplasias intraepiteliais cervicais (NICs) de baixo ou alto grau, carcinoma cervical, vaginal e anal. Os tratamentos atuais para as NICs ainda são muito invasivos e destrutivos. Sendo assim, existe a necessidade do desenvolvimento de modalidades menos agressivas. A terapia fotodinâmica (TFD) atende a esses pedidos, induzindo a morte seletiva de células infectadas pelo vírus. Este artigo tem o objetivo de analisar a redução da carga viral de HPV em pacientes com lesões intraepiteliais cervicais de alto grau (LIEAG) antes e após a TFD. Métodos: Foram incluídas 28 pacientes portadoras de NICs de alto grau que realizaram tratamento com 2,5 g de creme contendo o pró-fármaco ácido 5-metil aminolevulínico (MAL) a 20%, por aproximadamente 10 horas, com posterior aplicação da luz de LED com comprimento de onda de 630 nm e irradiância de 120 mW/cm2, por 25 minutos, entregando uma dose total de 180 J/cm2, em duas sessões. As pacientes foram avaliadas por meio de captura híbrida antes e após a TFD. Resultados: Após análise criteriosa, observou-se redução significativa da carga viral dos HPVs de alta oncogenicidade após a TFD (P = 0,0334) nas pacientes com LIEAG. O mesmo não foi observado em relação aos HPVs de baixo grau oncogênico (P = 0,4038). Conclusão: A TFD parece ser eficaz e promissora na diminuição da carga viral em pacientes com LIEAG induzidos por subtipos de HPV de alto grau oncogênico.

The assessment of psychology, quality of life in acne patients and evaluation of ALA-PDT for moderate to severe acne.

OBJECTIVE: To evaluate the state of psychology and quality of life of patients effected by acne and also the efficacy and safety of photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) for moderate to severe acne patients. METHODS: In the questionnaire part, a pre-designed form was filled out. The questionnaire was comprised of 2 sections related to acne including sociodemographic and disease information as well as Cardiff Acne Disability Index (CADI) and Self-Rating Anxiety Scale (SAS). In the trial part, the ALA-PDT was applied to moderate to severe acne patients. Fresh 5% ALA solution was topically applied to face or face & neck. After 1 h's incubation, a LED device was illuminated. A power density of 60-100 mW/cm2 was delivered for 20 min. All the patients finished 3-4 sessions of ALA-PDT at 7-10 days intervals. Non-invasive detections were taken for skin moisture, oil, and VISIA indexes. Adverse events were recorded during and after the treatment. RESULTS: A total of 247 acne patients finished questionnaires. Over 97 % patients were assessed as mild to severe impacts in CADI questionnaire and 37.6 % patients had various degrees of anxiety in SAS questionnaire. The higher the BMI was, the higher the CADI points were (G = 0.278, p = 0.005). The severity of acne was correlated with psychology and quality of life (CADI: G = 0.367, p = 0.000; SAS: G = 0.285, p = 0.003). A total of 116 patients with moderate or severe acne accepted ALA-PDT and completed at least 3 sessions (PDT3) or even PDT4. After 1 session of treatment (AT1) and AT2, the efficiencies of all patients were 5.2 % and 29.3 %. For patients with PDT3, the efficiencies at follow-up at 1st month after last session (FU1), FU2 and FU3 were 59.4 %, 66.7 % and 78.3 %, respectively. For patients with PDT4, the efficiencies at AT3 and FU1-3 were 51.3 %, 63.6 %, 76.5 % and 85.7 %, respectively. The efficacies of PDT4 patients showed an increasing trend from FU1 to FU3 (G = 0.480, p = 0.004). Acne lesions of mild to severe were correlated with the treatment efficacies (FU1: G = 0.354, p = 0.000; FU2: G = 0.474, p = 0.000; FU3: G = 0.397, p = 0.000). Nearly 15 % patients were followed up for 12 months and among them 52.9 % patients were able to maintain ≥90 % improvement rate. There were no statistically significant differences before and after treatment (p > 0.05) according to the skin moisture content, oil content, ultraviolet ray spots, brown spots, red areas, and purple textures measured. The adverse reactions of ALA-PDT, including local burning sensation, mild pain sensation, mild edema erythema, reactive acne, pigmentation, etc., were temporary and tolerable. CONCLUSION: In our study, 97.2 % patients were rated as impact in CADI questionnaire and 37.6 % patients had anxiety in SAS questionnaire. It is necessary to control weight and disease progression. The efficiencies of ALA-PDT for moderate and severe acne were 59.4%-85.7% at follow-ups of 1st, 2nd or 3rd month after last session. The adverse reactions of ALA-PDT were temporary and tolerable.

Retrospective German claims data study on initial treatment of bladder carcinoma (BCa) by transurethral bladder resection (TURB): a comparative analysis of costs using standard white light- (WL-) vs. blue light- (BL-) TURB.

PURPOSE: Photodynamic diagnosis using hexaminolevulinate (HAL)-guided BL-TURB may reduce the recurrence risk in non-muscle invasive BCa compared to standard WL-TURB due to more sensitive tumor detection. The impact of the initial use of WL- vs. BL-TURB on follow-up costs was evaluated in this real-world data analysis. METHODS: Anonymous claims data of German statutory health insurances (GKV) from 2011 to 2016 were analyzed in a primary and adjusted study population. Selection criteria included five quarters before enrolment, one index quarter (InQ) of initial TURB and BCa diagnosis, either within two years for the primary analysis or within four years for the adjusted analysis, and a follow-up period (FU) of either eleven or three quarters, respectively. RESULTS: In the primary analysis (n = 2331), cystectomy was identified as an important cost driver masking potential differences between cohorts. Therefore, patients undergoing cystectomy (InQ + FU) were excluded from the adjusted study population of n = 4541 patients (WL: 79%; BL: 21%). Mean total costs of BL-TURB were initially comparable to WL-TURB (WL: EUR 4534 vs. BL: EUR 4543) and tended to be lower compared to WL-TURB in the first two quarters of FU. After one year (3rd FU quarter), costs equalized. Considering total FU, mean costs of BL-TURB were significantly lower compared to WL-TURB (WL: EUR 7073 vs BL: EUR 6431; p = 0.045). CONCLUSION: This retrospective analysis of healthcare claims data highlights the comparability of costs between BL-TURB and WL-TURB.