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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. [ABSTRACT FROM AUTHOR]

Introduction: Cisplatin-based chemotherapy was established in the 1980s, and it has been improved by the development of a short hydration protocol in lung cancer therapy. However, cisplatin-based chemotherapy is still associated with renal toxicity. Because 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) is known to be a mitochondrial activator and a heme oxygenase-1 (HO-1) inducer, 5-ALA with SFC is speculated to mitigate cisplatin-induced renal inflammation. Methods: We investigated the effects of oral administration of 5-ALA with SFC for preventing cisplatin-based nephrotoxicity in patients with lung cancer and evaluated its benefits for patients who received cisplatin-based chemotherapy. The primary endpoint was the significance of the difference between the serum creatinine (sCr) levels of the patients administered 5-ALA with SFC and those given placebo after course 1 of chemotherapy. The difference in the estimated glomerular filtration rate (eGFR) between the two groups was also evaluated as the secondary endpoint. Results: The double-blind, randomized two-arm studies were conducted at 15 medical facilities in Japan; 54 male and 20 female patients with lung cancer who received cisplatin-based chemotherapy between the ages of 42 and 75 years were included in the study. The compliance rate was greater than 94% in the primary assessment and subsequent drug administration periods. All enrolled patients completed the four cycles of cisplatin-based chemotherapy with short hydration. The average level of sCr on day 22 of course 1 was 0.707 mg/dL in the group treated with 5-ALA and SFC and 0.735 mg/dL in the placebo group, respectively, and the sCr in the test group was significantly lower than that in the placebo group (p = 0.038). In addition, the eGFR was significantly higher in the SPP-003 group than in the placebo group up to day 1 of course 3 (84.66 and 75.68 mL/min/1.73 m2, respectively, p = 0.02) and kept better even after the last administration of the study drug (82.37 and 73.49 mL/min/1.73 m2, respectively, p = 0.013). Conclusions: The oral administration of 5-ALA with SFC is beneficial to patients undergoing cisplatin-based chemotherapy for lung cancer with short hydration. [ABSTRACT FROM AUTHOR]

Gastric cancer is the second most common cancer in Japan. The incidence of gastric cancer remains high owing to the increase in the elderly population. Endoscopy outperforms radiography in identifying early gastric cancer (EGC). Furthermore, image-enhanced endoscopy (IEE) has been developed and implemented worldwide in clinical practice. Magnifying IEE images can help to visualize the microvascular pattern and microstructure architecture, which is used for the characterization of EGC. However, accurate endoscopic diagnosis requires the experience and skill of endoscopists, making an objective and simple diagnostic method desirable. In this retrospective study, we investigated the diagnostic yield of 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) for identifying gastric cancers and high-grade adenomas. In total, 52 lesions from 43 patients were ultimately included in the study. We detected 5-ALA-mediated protoporphyrin IX fluorescence in 45 of the 52 lesions that were initially intended for PDD, resulting in a detection rate of 86.5%, whereas each signet ring cell carcinoma was negative using 5-ALA PDD. In eight of the patients with multiple lesions, 17 lesions were identified using 5-ALA PDD. Again, we took biopsies from six areas that we suspected as new lesions. While 4 lesions were gastric neoplasms resected by endoscopic submucosal dissection, two other lesions were normal. Preoperative 5-ALA-PDD could provide additional diagnostic yields to detect such multiple lesions simultaneously. No severe adverse events were observed. Prospective multicenter studies are warranted to confirm the usefulness of 5-ALA PDD for EGC identification. [ABSTRACT FROM AUTHOR]

Background: The advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system.Methods: We carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated.Results: A total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS).Conclusions: Our results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system.Trial Registration: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803-002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205). [ABSTRACT FROM AUTHOR]

5-aminolevulinic acid (ALA) is a natural amino acid and a product of the first heme synthesis pathway in mitochondria. Its immunomodulatory effects have garnered recent attention for their potential application to cancer, inflammation, and autoimmune diseases in humans. A supplement containing ALA is now available in Japan to enhance ATP synthesis via mitochondrial activity. However, how ALA affects canine immunity is unclear. Here we studied the effects of ALA on peripheral blood mononuclear cells (PBMCs) from healthy dogs in vitro. Heme oxygenase-1 (HO-1) protein was expressed in Madin-Darby canine kidney (MDCK) cells and PBMCs treated with ALA and ferrous sodium citrate (SFC), which showed that ALA works in dogs as well as humans. ALA also induced concanavalin A (ConA)-stimulated PBMCs to produce significantly more interferon-gamma (IFN-γ). Next-generation RNA sequencing (RNA-seq) revealed that ALA enhanced T cell immunity among Th1, Th2, and Th17 subsets, especially the IL-17 signaling pathway. We then confirmed that ALA promoted interleukin (IL)− 17A production in ConA-stimulated PBMCs. Together, these findings indicate that ALA promotes heme synthesis in mitochondria and enhances ConA-induced T cell immune responses in canine PBMCs. • 5-aminolevulinic acid (ALA) upregulates the heme synthesis pathway in dogs. • ALA enhances the expression of inflammatory cytokines induced by T cell activation. • ALA treatment especially upregulates the Th17 response in dogs. [ABSTRACT FROM AUTHOR]

Objects: Recently, we reported that diagnostic laparoscopy with photodynamic diagnosis using oral 5-aminolevulinic acid (ALA-PDD) is a promising tool for diagnosing early peritoneal metastases in gastric cancer. The present study evaluated the usefulness of adding ALA-PDD to conventional diagnostic laparoscopy and assessed the association of the ALA-PDD results with peritoneal fluid cytology and molecular diagnostic testing. Methods: Diagnostic laparoscopy using sequential white light (WL) and ALA-PDD observations was performed in 52 advanced gastric cancer patients, and the sensitivity of ALA-PDD for detecting peritoneal disease was compared to WL. Peritoneal fluid samples from the same patients were also subjected to cytological examination and molecular diagnosis using a transcription-reverse transcription concerted reaction (TRC). Results: Twenty-four of the 52 patients (46%) had no macroscopic evidence of peritoneal metastases on WL examination; however, ALA-PDD detected dissemination in 5 of these 24 patients (21%) (pd-P). Cytological examination was negative in 4 of the 5 pd-P patients, and molecular testing using TRC was negative in 3 of the 5 pd-P patients. Conclusions: This study demonstrated that diagnostic laparoscopy with ALA-PDD improved the sensitivity for the detection of peritoneal metastases. ALA-PDD may be a useful technique for the preoperative staging of advanced gastric cancer and can complement examinations of peritoneal lavage fluids. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: 5-Aminolevulinic acid (ALA)-mediated photodynamic diagnosis (PDD) has recently been approved in Japan for the management of non-muscle invasive bladder cancer. As such, the current study aimed to investigate the real-world diagnostic accuracy and safety of ALA-PDD-assisted transurethral resection of bladder tumor (TURBT)., Methods: A total of 76 patients who underwent PDD-assisted TURBT were enrolled. ALA (20 mg/kg body weight) was orally administered before TURBT. Fluorescence observation and tissue collection were performed during surgery, after which diagnostic accuracy was determined. Potential side effects of ALA, including vomiting, hypotension, and liver toxicity, were carefully monitored., Results: The sensitivity, specificity, positive predictive value, and negative predictive value for detecting urothelial carcinoma were 90.1 %, 61.2 %, 55.1 %, and 92.2 % for fluorescence light (FL) and 65.4 %, 88.9 %, 75.7 %, and 83.9 %, for white light (WL) respectively. The mean number of tumors detected per patient was 1.92 and 1.39 for FL and WL (p < 0.05), respectively. No significant differences in the FL sensitivity and specificity were observe among the three patient groups classified according to ALA exposure time after oral administration (2-3, 3-4, and >4 h). ALA-related adverse effects included vomiting (seven cases), hypotension (seven cases, two of which were severe), and liver toxicity (four cases). All side effects disappeared shortly after standard treatment., Conclusion: ALA-PDD showed sufficient diagnostic accuracy even after more than 4 h of ALA exposure prior to surgery, as well as acceptable safety profiles., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Study Objective: To examine the diagnostic accuracy of hysteroscopic photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5ALA) in patients with endometrial cancer and premalignant atypical endometrial hyperplasia., Design: A single-center, open-label, exploratory intervention study., Setting: University Hospital in Japan., Patients: Thirty-four patients who underwent hysteroscopic resection in the Department of Obstetrics and Gynecology at Keio University Hospital., Interventions: Patients were given 5ALA orally approximately 3 hours before surgery and underwent observation of the uterine cavity and endometrial biopsy using 5ALA-PDD during hysteroscopic resection. Specimens were diagnosed histopathologically and the diagnostic sensitivity and specificity of hysteroscopic 5ALA-PDD for malignancy in the uterine cavity was determined. Red (R), blue (B), and green (G) intensity values were determined from PDD images, and the relationships of histopathological diagnosis with these values were used to develop a model for objective diagnosis of uterine malignancy., Measurements and Main Results: Three patients were excluded from the study because of failure of the endoscope system. A total of 113 specimens were collected endoscopically. The sensitivity and specificity of 5ALA-PDD for diagnosis of malignancy in the uterine cavity were 93.8% and 51.9%, respectively. The R/B ratio in imaging analysis was highest in malignant lesions, followed by benign lesions and normal uterine tissue, with significant differences among these groups (p <.05). The R/B and G/B ratios were used in a formula for prediction of malignancy based on logistic regression and the area under the receiver operating characteristic curve for this formula was 0.838. At a formula cutoff value of 0.220, the sensitivity and specificity for diagnosis of malignant disease were 90.6% and 65.4%, respectively., Conclusion: To our knowledge, this is the first study of the diagnostic accuracy of 5ALA-PDD for malignancies in the uterine cavity. Hysteroscopic 5ALA-PDD had higher sensitivity and identifiability of lesions. These findings suggest that hysteroscopic 5ALA-PDD may be useful for diagnosis of minute lesions., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the utility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) to detect gastric/colorectal tumors., Methods: This prospective single-center study investigated inter-subject variability in patients with early-stage gastric/colorectal tumor indicated for endoscopic resection. Subjects were patients with gastric or colorectal tumors who had undergone endoscopic resection between November 2012 and November 2013. Selection criteria included age 20-80 years, either sex, and provision of informed consent. Patients were orally administered 20 mg/kg of 5-ALA enteric-coated capsules (SBI ALApromo Co., Tokyo, Japan). Administration of 5-ALA was followed by endoscopic resection of gastric or colorectal tumors, and the resected specimens were examined using a video autofluorescence processor and a fluorescence endoscope (SAFE-3000 and EB-1970AK, respectively; Pentax, Tokyo, Japan). The primary endpoint was the presence of fluorescence in tumors. Endoscopic, macroscopic, and histopathologic findings of tumors were assessed. We also evaluated adverse events of the present procedure as a secondary endpoint and examined each patient for the presence of known adverse effects of 5-ALA, namely, hematocytopenia, liver dysfunction, hypotension, nausea, and photosensitivity., Results: We enrolled 10 patients (7 men, 3 women) (n = 13 lesions: 10 gastric/3 colorectal tumors). Fluorescence was detected in 7/13 (53.8%) lesions. No significant differences in sex (male: 55.6% vs female: 50.5%, P = 1.00), age (67.1 ± 1.9 years vs 65.0 ± 2.0 years, P = 0.45), tumor color (reddish: 60.0% vs discolored: 33.3%, P = 0.56), tumor diameter (15.0 ± 2.1 mm vs 14.2 ± 2.3 mm, P = 0.80), macroscopic type (protruded: 70.0% vs depressed 0%, P = 0.07), histologic type (differentiated type: 58.3% vs 0%, P = 0.46), invasion depth (mucosal layer: 55.6% vs submucosal layer: 33.3%, P = 1.00), lymphatic invasion (present: 33.3% vs absent: 50.0%, P = 1.00), venous invasion (present: 0% vs absent: 54.5%, P = 1.00) or procedure time of endoscopic resection (36.3 ± 8.3 min vs 36.7 ± 9.0 min, P = 0.98) were observed between the patients with and without fluorescence. Fluorescence detection rate tended to be high for elevated lesions. Liver dysfunction developed in 4/10 (40.0%) patients. The extent of the liver dysfunction was a slight increase in transaminases and total bilirubin levels, which spontaneously improved in the patients. None of the patients developed photosensitivity., Conclusion: Results of this preliminary study suggest the utility of PDD using 5-ALA for screening of gastric and colorectal cancers.