Incidence and predictors of intraoperative hypotension during transurethral bladder tumor resection with oral 5-aminolevulinic acid.

OBJECTIVES: To analyze the incidence and risk factors of intraoperative hypotension related to photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) with oral 5-aminolevulinic acid (5-ALA). METHODS: We retrospectively analyzed 487 patients with bladder tumors who underwent PDD-TURBT (n = 184) or conventional TURBT (conv-TURBT) (n = 303) between 2018 and 2021. Intraoperative hypotension was defined as hypotension requiring vasopressors during TURBT, and its incidence was compared between the two groups. Potential risk factors of intraoperative hypotension, including preoperative change in mean arterial pressure (MAP), were further investigated in patients receiving PDD-TURBT. RESULTS: The median age was 72 years, 392 patients (81%) were male, and 203 (42%) had hypertension. TURBT was performed under general and spinal anesthesia in 76 (16%) and 411 (84%) patients, respectively. The incidence of intraoperative hypotension was significantly higher in PDD-TURBT compared to conv-TURBT (43% vs. 17%, respectively). The median change in MAP until the induction of anesthesia was +6.5 mmHg (range: -29.0 to +46.3) in the PDD-TURBT group and +14.7 mmHg (range: -35.3 to +67.7) in the conv-TURBT group, showing a significantly smaller increase in the PDD-TURBT group (p < 0.001). In the multivariable analysis for PDD-TURBT patients, advanced age, general anesthesia, and lower MAP change (<+6.5 mmHg) until anesthesia induction were significantly associated with intraoperative hypotension (p = 0.0104, <0.001, and <0.001, respectively). CONCLUSIONS: Intraoperative hypotension occurred more frequently in patients who underwent PDD-TURBT than in those who underwent conv-TURBT. Using oral 5-ALA decreases preoperative blood pressure elevation and may be responsible for intraoperative hypotension.

Adverse effects of topical photodynamic therapy in rosacea - Case report.

Rosacea is a chronic and inflammatory skin condition, with relapses being a common characteristic. Its treatments are based on cosmetics, drugs, and the application of procedures based on high-powered light. Photodynamic Cosmetic Therapy (PCT) combines light, a photosensitizer (PS), and molecular oxygen present in tissues, generating photochemical reactions capable of causing tissue and vascular destruction, stimulating tissue repair. We report a case with an adverse effect caused by applying PCT, using 2 % 5-aminolevulinic acid (ALA 2 %), and irradiated with amber LED light associated with infrared radiation for the control of rosacea. A patient with subtype II rosacea underwent PCT treatment of 3 sessions at 21-day intervals, being evaluated using photographic images and Wood's lamp. In the first session of the therapy, an exacerbated inflammatory process was observed. Such an adverse event is estimated to be as a result of the patient using ointment containing corticosteroids for a short period. With the use of medications, it was possible to recover the appearance of the skin thoroughly, and after 21 days, the treatment sessions were performed again. Despite the complication that affected the patient in this study, positive effects were found after the pharmacological therapeutic measures were adopted.

[Effectiveness of Pharmaceutical Intervention While Administering 5-Aminolevulinic Acid Hydrochloride through a Collaboration of Physicians and Pharmacists].

5-aminolevulinic acid hydrochloride is a highly effective drug in reducing tumor residuals in transurethral resection of the bladder tumors; however, hypotension is a serious side effect that causes clinical problems. To avoid serious side effects, a pharmacist, in consultation with a physician, decided to discontinue the antihypertensive medication, and the effect of this pharmaceutical intervention was examined retrospectively. This study included patients who received 5-aminolevulinic acid hydrochloride at Gifu Municipal Hospital and were instructed to continue receiving their usual antihypertensive medication on the day of surgery. The control group comprised 17 patients before the pharmaceutical intervention, and the intervention group comprised 18 patients after the pharmaceutical intervention. The difference in systolic blood pressure before and after 5-aminolevulinic acid hydrochloride administration was -19.4±22.5 mmHg in the control group and -2.8±16.0 mmHg in the intervention group. The intervention group showed a significantly lower decrease in blood pressure(p=0.019). Intervention to avoid hypotension through the collaboration between physicians and pharmacists may be effective in improving the safety of 5-aminolevulinic acid hydrochloride.

The impact of photodynamic therapy on skin homeostasis in patients with actinic keratosis: A prospective observational study.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AKs), but there is little information on how PDT affects skin barrier function. The objectives of this study are: To compare skin barrier function between skin with AKs and healthy skin and to evaluate the impact of PDT on skin homeostasis in patients with AKs. METHODS: A prospective observational study was conducted in patients with AKs to evaluate epidermal barrier function and skin homeostasis before and 1 ek after receiving PDT. RESULTS: A total of 21 subjects were included in the study, male/female ratio was 17:4, mean age was 75.86 years. The number of AKS observed before starting treatment was reduced with respect to those diagnosed 1 month after starting PDT (14.83 vs. 1.91, p < 0.0001). Application of PDT for treating AKs modifies epidermal barrier function. Immediately after the first session temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH) and total antioxidant capacity (TAC) increased while pH decreased on lesional skin. After 1-month follow-up, the only remained change was the increased in SCH. Higher increases in temperature were observed when using occlusive PDT compared to mixed modality. 5-ALA and M-ALA seem to have a similar impact on skin barrier. CONCLUSIONS: PDT can improve skin barrier function in patients with AKs. Skin homeostasis parameters can be used to assess efficacy and optimize dosing.

The Interventions to Minimize Pain During Photodynamic Therapy With 5-Aminolevulinic Acid for the Treatment of Cutaneous Diseases.

Photosensitization with 5-aminolevulinic acid (ALA) combined with photodynamic therapy (PDT) is approved in the United States for the treatment of actinic keratosis (AK) and is used off-label for other indications including acne treatment and photo rejuvenation. However, pain, particularly during the initial illumination period, limits the utility of this highly efficacious therapy. Although modifications to conventional ALA-PDT protocols that improve tolerability without diminishing efficacy have been identified, few have been evaluated in randomized, controlled trials, and the number of variables involved in ALA incubation (eg, duration, occlusion, ALA formulation, and strength) and PDT illumination (eg, light source, fluence rate, irradiance, and duration) confounds standardization.  Perhaps the most promising modifications to date involve continuous activation of low levels of protoporphyrin IX, the photoactive metabolite of ALA, as well as using shorter incubation times (with or without prolongation of illumination), lower irradiance, and daylight or combined (daylight and conventional) PDT. However, reimbursement of PDT with alternative light sources in the US is hampered by the US Food and Drug Administration (FDA) labeling, which specifies the blue or red light devices approved for use with corresponding marketed ALA 20% solution and 10% gel, respectively. This review summarizes the existing evidence with respect to pain control in patients undergoing ALA-PDT, recommendations from clinical experience, and goals for future research. J Drugs Dermatol. 2023;22(11):1082-1087   doi:10.36849/JDD.7637.

Modified red light 5-aminolevulinic acid photodynamic therapy versus low-dose isotretinoin therapy for moderate to severe acne vulgaris: A prospective, randomized, multicenter study.

BACKGROUND: Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) and isotretinoin (ISO) are effective treatments for moderate to severe acne vulgaris. OBJECTIVE: To evaluate the efficacy and adverse effects of M-PDT and ISO for moderate to severe acne vulgaris. METHODS: A multicenter, randomized clinical trial was conducted with participants randomly assigned to the M-PDT group (up to 5 weekly sessions following manual comedone extraction) or the ISO group (oral ISO, 0.5 mg/kg/d for 6 months) and followed up to 6-months after therapy. RESULTS: A total of 152 patients were allocated. The overall effective rates in the M-PDT group were significantly higher than the ISO group at 1 month (67.74% vs 10.26%), whereas the opposite was the case 1 month after treatment (75.81% vs 97.44%). Time to achieve 50% lesion improvement in the M-PDT group was significantly less than the ISO group (1 vs 8 weeks). Overall, 70.67% of the ISO group patients experienced systemic side effects such as hepatotoxicity, whereas side effects were skin-limited in the M-PDT group. LIMITATIONS: Limitations of this study included relatively low numbers of participants and high withdrawal rate. CONCLUSION: M-PDT offers a more rapid onset of improvement, comparable overall efficacy, good tolerability, and comparable durability of response compared with ISO.

Oral 5-aminolevulinic acid administration before transurethral resection of bladder tumor induces perioperative nausea and vomiting.

BACKGROUND: The efficacy of photodynamic diagnosis using 5-aminolevulinic acid during transurethral resection of bladder tumors has been demonstrated, albeit with limited information regarding its side effects. This study aimed to clarify the impact of oral 5-aminolevulinic acid on perioperative nausea and vomiting (NV) for the first time in a real-world clinical practice setting. METHODS: Patients who underwent transurethral surgery at Kagawa University between April 2017 and March 2020 were included. Perioperative NV and antiemetic use status were prospectively assessed and compared between the patients who received oral 5-aminolevulinic acid and those who did not. Additionally, univariate and multivariate analyses were performed for predicting postoperative nausea and vomiting. RESULTS: Of 214 patients, 74 (34.6%) received oral 5-aminolevulinic acid preoperatively. The proportions of preoperative NV and antiemetic use in the patients who received 5-aminolevulinic acid were 9.5% and 4.1%, respectively, and higher than in those who did not (0% and 0%; P < 0.01 and P = 0.04, respectively). Postoperative NV (25.7%) and antiemetics use (8.0%) ratios in the patients who received 5-aminolevulinic acid were significantly different from those in the non-users group (3.6% and 2.1%, P < 0.01 and P < 0.01, respectively). Although no differences in risk factors were found for postoperative NV between the two groups, multivariate analyses indicated 5-aminolevulinic acid use as an independent predictive factor for postoperative NV (odds ratio, 11.5; 95% confidence interval, 3.98-33.3; P < 0.01). CONCLUSIONS: Our study clearly showed that oral administration of 5-aminolevulinic acid was associated with perioperative NV even without risk factors, highlighting the need for addressing its application.

Incidence of perioperative hypotension in patients undergoing transurethral resection of bladder tumor after oral 5-aminolevulinic acid administration: a retrospective multicenter cohort study.

PURPOSE: Tumors can be visualized using 5-Aminolevulinic acid hydrochloride (5-ALA) during transurethral resection of bladder tumors (TURBT). Hypotension is an adverse effect of 5-ALA; however, its incidence and morbidity rates are unknown. This study aimed to describe the incidence of perioperative hypotension and identify risk factors for hypotension among patients after 5-ALA administration in TURBT. METHODS: This retrospective multicenter cohort study was conducted at three general hospitals in Japan. Adult patients who underwent elective TURBT after 5-ALA administration between April 2018 and August 2020 were included. The primary outcome was the incidence of perioperative hypotension (mean blood pressure < 65 mmHg). The secondary outcomes were the use of vasoactive agents and adverse events, including urgent intensive care unit (ICU) admission. Multivariate logistic regression analysis was performed to investigate risk factors of the incidence of intraoperative hypotension. RESULTS: The median age of 261 patients was 73 years. General anesthesia was induced in 252 patients. The intraoperative hypotension was observed in 246 (94.3%) patients. Three patients (1.1%) were urgently admitted to the ICU for continued vasoactive agent use after surgery. All three patients had renal dysfunction. Multivariate logistic regression analysis revealed that general anesthesia was significantly associated with intraoperative hypotension (adjusted odds ratio, 17.94; 95% confidence interval, 3.21-100.81). CONCLUSION: The incidence of hypotension in patients undergoing TURBT after 5-ALA administration was 94.3%. The incidence of urgent ICU admission with prolonged hypotension was 1.1% in all patients with renal dysfunction. General anesthesia was significantly associated with intraoperative hypotension.

Efficacy and Safety of 5-Aminolevulinic Acid Combined with Iron on Skeletal Muscle Mass Index and Physical Performance of Patients with Sarcopenia: A Multicenter, Double-Blinded, Randomized-Controlled Trial (ALADDIN Study).

Sarcopenia is a geriatric syndrome characterized by decreased physical performance, muscle mass, and strength. Since the intake of 5-aminolevulinic acid (ALA) with iron can increase muscle mass and mitochondria in mice and elevate physical exercise performance in humans, the beneficial effects of ALA in patients with sarcopenia are expected, but this remains unexplored in the literature. This study aimed to assess the efficacy and dose dependency of ALA combined with iron in sarcopenia by measuring skeletal muscle mass index (SMI). Subjects with sarcopenia were enrolled and randomized into the ALA and sodium ferrous citrate (SFC) intake groups (ALA50/SFC29, ALA100/SFC29, ALA150/SFC29, ALA 100/SFC57, and ALA0/SFC29 placebo) and ingested the assigned study food for 12 weeks. The primary endpoint, the change in SMI from baseline to week 12, did not differ significantly between the groups. Hand grip significantly increased or tended to increase from baseline after 12 weeks with all doses of ALA or SFC compared with the placebo group. No consistent changes were observed in the other endpoints, including calf circumference, physical function, or quality of life (QOL). Although this study suggests safe administration and the possibility of ALA improving hand grip strength in patients with sarcopenia, further investigation is required.

5-Aminolevulinic acid photodynamic therapy versus minocycline for moderate-to-severe rosacea: A single-center, randomized, evaluator-blind controlled study.

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) showed potential to treat rosacea according to recent studies; however, a lack of clinical evidence and unclear adverse effects limit its use. OBJECTIVE: To compare the effect of ALA-PDT vs minocycline on rosacea. METHODS: In this single-center, randomized, evaluator-blind, controlled study, patients with moderate-to-severe rosacea were allocated to receive 3 to 5 sessions of ALA-PDT or 8 weeks of 100 mg daily minocycline treatment, followed by a 24-week follow-up. RESULTS: Of all the 44 randomized patients, 41 received complete treatment (ALA-PDT: 20 and minocycline: 21 patients). At the end of treatment, ALA-PDT showed noninferior improvement of papulopustular lesions and Rosacea-specific Quality of Life compared with minocycline (median reduction of lesion count: 19 vs 22, median change of Rosacea-specific Quality of Life score: 0.48 vs 0.53). The Clinician's Erythema Assessment success of ALA-PDT was lower than that of minocycline's (35% vs 67%). Demodex density and relapse rate were comparable in both groups. Erythema, mild pain, and exudation were the most common adverse reactions of ALA-PDT. LIMITATIONS: Limited sample size restricted us from drawing further conclusions. CONCLUSION: As minocycline does, ALA-PDT can improve rosacea mainly in papulopustular lesions and patients' quality of life, indicating a new option for rosacea.

Topical photodynamic therapy for brachytherapy-induced oral mucositis.

Radioactive iodine-125 seed implantation has emerged as an effective treatment approach for locally advanced oral cancer. Nevertheless, some brachytherapy associated side reactions were reported, even at a relatively low initial radiation treatment volume. Radiogenic oral mucositis has been a concerning side effect of this treatment method. Photodynamic therapy (PDT) is a potential viable therapeutic strategy of oral mucositis. Herein, we report a case of 73-year-old male patient with ventral tongue and floor-of-the mouth cancer treated by iodine-125 implantation. Thereafter, this patient experienced radiation-induced oral mucositis. After being treated with four sessions of topical 5-aminolevulinic acid (ALA) PDT, this case was completely cured and followed up for 6-month with no recurrence.

5-Aminolevulinic acid hydrochloride enhances bupivacaine-induced hypotension in spontaneously hypertensive rats.

PURPOSE: Oral administration of 5-aminolevulinic acid hydrochloride (5-ALA-HCl) has been reported to enhance the hypotensive effects associated with anesthetics, especially in elderly hypertensive patients treated with antihypertensive agents. The present study aimed to clarify the effects of antihypertensive-agent- and anesthesia-induced hypotension by 5-ALA-HCl in spontaneously hypertensive rats (SHRs). METHODS: We measured blood pressure (BP) of SHRs and normotensive Wistar Kyoto (WKY) rats treated with amlodipine or candesartan before and after administration of 5-ALA-HCl. We also investigated the change in BP following intravenous infusion of propofol and intrathecal injection of bupivacaine in relation to 5-ALA-HCl administration. FINDINGS: Oral administration of 5-ALA-HCl significantly reduced BP in SHRs and WKY rats with amlodipine and candesartan. Infusion of propofol significantly reduced BP in SHRs treated with 5-ALA-HCl. Intrathecal injection of bupivacaine significantly declined SBP and DBP in both SHRs and WKY rats treated with 5-ALA-HCl. The bupivacaine-induced decline in SBP was significantly larger in SHRs compared with WKY rats. CONCLUSION: These findings suggest that 5-ALA-HCl does not affect the antihypertensive agents-induced hypotensive effect, but enhances the bupivacaine-induced hypotensive effect, especially in SHRs, indicating that 5-ALA may contribute to anesthesia-induced hypotension via suppression of sympathetic nerve activity in patients with hypertension.

Risks and benefits of transurethral resection of the bladder tumor using photodynamic diagnosis with oral 5-aminolevulinic acid hydrochloride according to age and history of recurrence in patients with non-muscle invasive bladder cancer.

BACKGROUND: Patient selection for transurethral resection of the bladder tumor using photodynamic diagnosis (PDD-TURBT) with oral 5-aminolevulinic acid (5-ALA) hydrochloride for non-muscle-invasive bladder cancer (NMIBC) is still unclear as to the best balance of risks (adverse events including hypotension) and benefits (reduction of intravesical recurrence). METHODS: This single-center retrospective study between April 2013 and March 2022, compared the intravesical recurrence-free survival between patients who underwent PDD-TURBT and WL-TURBT using propensity score matching. RESULTS: A total of 222 patients who underwent PDD-TURBT and 177 patients who underwent WL-TURBT for NMIBC were included. Propensity score matching was used to compare intravesical recurrence-free survival in 119 NMIBC patients in the both treatment groups. The intravesical recurrence-free survival within 500 days was significantly higher in the PDD-TURBT group than in the WL-TURBT group (P = 0.039; hazard ratio [HR] 0.48 [0.23-0.98]). Subgroup analysis showed that PDD-TURBT contributed to the reduction of short-term intravesical recurrence in patients aged < 75 years (P = 0.02; HR 0.22 [0.06-0.79]) and primary disease (P = 0.038; HR 0.35 [0.13-0.94]). Hypotension with a systolic blood pressure of < 80 mmHg was observed in 79 patients (35.6%) during PDD-TURBT surgery. In particular, age ≥75 years and general anesthesia were independent prognostic factors for predicting intraoperative hypotension. CONCLUSIONS: PDD-TURBT reduced short-term intravesical recurrence in NMIBC, whereas a higher frequency of hypotension was found in patients aged ≥ 75 years. These results suggest that the risks and benefits of PDD-TURBT are well balanced in younger patients (< 75 years) and those with primary disease.

Efficacy of two different methods of cold air analgesia for pain relief in PDT of actinic keratoses of the head region - a randomized controlled comparison study.

BACKGROUND: Photodynamic therapy (PDT) is an effective method for treating actinic keratosis (AK) with pain during illumination representing the major side effect. The efficacy of two different cooling methods for pain relief in PDT of AK in the head region was compared. METHODS: Randomized, assessor-blinded, half side comparison study in 20 patients with symmetrically distributed AK on the head. Conventional PDT was performed on both halves of the scalp or face by applying 20% aminolevulinic acid cream (ALA) and subsequent illumination with incoherent red light. During illumination one side was cooled with a cold air blower (CAB) and the other with a standard fan (FAN) in a randomized fashion. Pain and skin temperature were recorded during and after PDT. The phototoxic skin reaction was evaluated up to seven days after PDT. The clearance rate of AK was assessed at 3 and 6 months after PDT. RESULTS: Mean pain (VASmean), maximum pain intensity (VASmax) and the mean skin temperature during PDT were significantly lower with CAB as compared to FAN (VASmean: 2.7 ± 1.4 vs. 3.7 ± 2.1, p = 0.003; VASmax: 3.8 ± 2.0 vs. 4.8 ± 2.5, p = 0.002; 26.8 ± 2.0 °C vs. 32.1 ± 1.7 °C; p=<0.001). The severity of the phototoxic skin reaction and the clearance rate of AK did not differ between the two cooling methods. CONCLUSION: Cooling with CAB during PDT has a greater analgesic effect than cooling with FAN. Patients with a lower skin temperature during illumination tended to experience less pain, however, this effect did not reach the level of statistical significance.

Evaluation of the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy in women with high-risk HPV persistent infection after cervical conization.

OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy (PDT) in women with high-risk human papillomavirus (hr-HPV) persistent infection after cervical conization, including loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC). MATERIALS AND METHODS: The clinicopathological and follow-up data of 76 women with hr-HPV persistent infection after cervical conization (54 cases with LEEP and 22 cases with CKC) were collected. All the women in this group met these criteria: postoperative pathological diagnosis of LEEP/CKC showed high grade squamous intraepithelial lesions (HSIL) with negative incisal margin, hr-HPV persistent infection after LEEP/CKC ≥ 1 year, colposcopy and histopathology showed no intraepithelial lesions before PDT, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with an interval of 7-10 days. The above patients were followed up 6 months and 12 months after PDT, and the follow-up contents included Roche Cobas HPV classification test, cytology, colposcopy, and pathological examinations. HPV negative conversion rate is an index to evaluate the efficacy of PDT. In addition, we also assessed the safety of PDT. RESULTS: Six months after PDT, the overall HPV clearance rate was 59.21% (45/76). The HPV negative conversion rates in patients ≤ 50 years old group and > 50 years old group were 68.52% (37/54) and 36.36% (8/22), respectively (P=0.009). But there was no significant difference in HPV clearance rate between the HPV16/18 infection group and other hr-HPV infection group (P=0.3326). 12 months after PDT, 1 case underwent hysterectomy because of progression to HSIL, and 7 cases lost follow-up. The overall HPV clearance rate was 88.24% (60/68). The negative conversion rates of HPV16/18 and other hr-HPV infection groups were 76.00% (19/25) and 95.35% (41/43), respectively (P=0.0458). However, the HPV negative conversion rate was not correlated with the patient's age (P=0.2383). The adverse reactions after PDT were mild, mainly manifested as increased vaginal secretions or burning/tingling. CONCLUSIONS: Photodynamic therapy could be an effective treatment for patients with hr-HPV persistent infection after cervical conization and it could promote the negative conversion of hr-HPV and prevent the recurrence progression of cervical intraepithelial neoplasia (CIN) after LEEP/CKC.

Counteracting Side-effects of Photodynamic Therapy for Actinic Keratoses.

BACKGROUND/AIM: Actinic keratoses (AKs) are precursors of squamous cell carcinomas and early intervention is important. Photodynamic therapy (PDT) is often first-choice treatment for widespread AKs. Classic PDT consists of: Superficial curettage, application of 5-aminolevulinic acid or methyl aminolevulinate, incubation and protoporphyrin IX (PpIX) accumulation under occlusion for 3 hours, followed by illumination with red light-emitting diode light (37 J/cm2). Classic PDT is effective in treating AKs, but side-effects include unpleasant pretreatment, severe pain during illumination, inflammation after treatment, and long waiting time in the clinic. MATERIALS AND METHODS: This targeted mini review describes efforts to counteract side-effects and simplify the procedure considering the clinic capacity. Changes are only acceptable if treatment effect is maintained. RESULTS: We introduce the following procedure changes: (i) reducing pre-treatment pain, bleeding, and oozing by omitting curettage; (ii) long-term illumination for 2 hours during PpIX formation (already in use as daylight PDT) and shortening of incubation time from 3 hours to 30 minutes to minimize pain and inflammation risk. In addition, options of timing, incubation, and illumination indoors and outdoors are discussed, focusing on advantages and disadvantages for patients and clinics. CONCLUSION: We report several options to counteract side-effects of classic PDT.

5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for acneform rash induced by erlotinib: A case report.

Erlotinib is an anticancer drug approved for the treatment of non-small cell lung cancer. It inhibits growth and proliferation of tumor cells by targeting epidermal growth factor receptor (EGFR). Dermatological toxicities are common side effects associated with EGFR inhibition. Here we describe a patient with acneform rash following oral medication of erlotinib, presented as facial erythema, papules and pustules. Two sessions of 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) with a 2-week interval were performed. No significant side effects or scarring were observed. The patient showed no recurrence within 6 months. Thus, we conclude that ALA-PDT is an effective treatment for skin lesions induced by erlotinib, especially for patients with need to sustain medication.

Safety of repeat blue light cystoscopy with hexaminolevulinate (HAL) in the management of bladder cancer: Results from a phase III, comparative, multi-center study.

PURPOSE: The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis. MATERIALS AND METHODS: All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P < 0.05 was considered statistically significant. RESULTS: HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09). CONCLUSIONS: Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy.

5-Aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis.

OBJECTIVES: To investigate the effects of pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis in rats. METHODS: Male Wistar rats (340-460 g) were pretreated with vehicle or with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (100/157 or 300/471 mg/kg/day, po) once daily for 7 days before cystometry. Saline or cyclophosphamide (150 mg/kg, ip) was administered 2 days before cystometry. Cystometry was performed under urethane anesthesia (0.8 g/kg, ip) via a catheter inserted into the bladder. After cystometry, bladder tissues were collected to perform hematoxylin and eosin staining for pathological evaluation (neutrophil infiltration, edema, and bleeding scores), and for enzyme-linked immunosorbent assay and real-time polymerase chain reaction for investigating tissue levels of myeloperoxidase, and mRNA levels of haem oxygenase-1 as a cytoprotective molecule. RESULTS: Compared to controls, cyclophosphamide induced a shorter intercontraction interval, lower bladder compliance, increased number of non-voiding contractions, and increased pathological scores and myeloperoxidase expression in the bladder. Pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (300/471 mg/kg/day) significantly improved cyclophosphamide-induced intercontraction interval shortening and increases in number of non-voiding contractions and neutrophil infiltration/bleeding scores and enhanced haem oxygenase-1 expression in the bladder. In addition, cyclophosphamide-induced decreases in bladder compliance and increases in myeloperoxidase were not detected with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate pretreatment. CONCLUSIONS: Pretreatment with 5-aminolevulinic acid expects protective effects on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis by improving inflammatory changes in bladder tissues perhaps via up-regulation of haem oxygenase-1.