Dangui Huoxue Preparation (DHP) Ameliorates Skin Fibrosis, Inflammation, and Vasculopathy in the Bleomycin-Induced Murine Model of Systemic Sclerosis.

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs and vasculopathy with poor prognosis. Dangui Huoxue Preparation (DHP) is a clinically effective traditional Chinese herbal formula for the treatment of SSc in the hospital. This study aims to investigate the therapeutic effects and underlying molecular mechanisms of DHP in the treatment of SSc. SSc mice models are induced by bleomycin (BLM). Tissues of DHP group, normal control group, and positive control drug Sanqi Tongshu Capsule (STC) group are collected for inflammation, fibrosis, and vasculopathy. Also, the human dermal fibroblasts (HDF) stimulated with TGF-ß1 are analyzed for in vitro study. The expression levels of MCP-1, IFN-γ, IL-1ß, IL-10, Fizz1, iNOS, and IL12p40, and the mRNA levels of Col1a1, Col1a2, Col3a1, and Col5a1 are significantly decreased in all DHP groups and STC group compare with those in the BLM group. The main drug of DHP inhibits the proliferation and migration of HDF, reduces Ctgf, Itgb3, Itgb5 expression, and also inhibits the Smad3 pathway. In conclusion, DHP can ameliorate SSc skin inflammation, fibrosis, and vasculopathy, possibly suppressing the TGF-ß1/Smad3 signaling pathway through extracellular and intracellular mechanisms.

Is Radiation Therapy Cost-Effective in the Positron Emission Tomography/Computed Tomography Era for Early-Stage Favorable Hodgkin Lymphoma With Alternative Payment Models?

PURPOSE: Despite multiple randomized trials, variation in practice remains regarding the most effective treatment for early-stage, favorable-risk Hodgkin lymphoma. With increasing emphasis on alternative payment models, we investigate the cost-effectiveness of chemotherapy alone versus combined modality therapy (CMT). METHODS AND MATERIALS: A Markov model was formed to compared 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) to 2 cycles of ABVD followed by 20 Gy in 10 fractions involved-site radiation therapy. Modalities were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs) and evaluated with a willingness to pay a threshold of $100,000 per QALY gained. RESULTS: The base case analysis showed that CMT is cost-effective compared with ABVD alone, with an incremental cost-effectiveness ratio of $8028 per QALY gained and an incremental cost of $236 gaining 0.029 QALYs. On sensitivity analyses, the results were the most sensitive to changes in recurrence rates. If the recurrence rate differences were ≥6%, CMT was cost-effective. CONCLUSIONS: CMT is a cost-effective strategy for early-stage, favorable-risk Hodgkin lymphoma based on currently available evidence. However, small variations in recurrence-rate estimates dramatically affect strategy cost-effectiveness.

Percutaneous Sclerotherapy with Bleomycin and Ethiodized Oil: A Promising Treatment in Symptomatic Giant Liver Hemangioma.

Background Percutaneous sclerotherapy with bleomycin has been proven to have a potential benefit in the management of low-flow venous malformations. Liver hemangiomas are considered low-flow venous malformations. Thus, percutaneous sclerotherapy could potentially have a promising result in their management. Purpose To investigate the feasibility, efficacy, and safety of percutaneous sclerotherapy with bleomycin in the management of symptomatic giant liver hemangioma (GLH). Materials and Methods This single-institute prospective study was conducted between September 2018 and July 2020. Percutaneous sclerotherapy was performed using a mixture of bleomycin and ethiodized oil under guidance of US and fluoroscopy in participants with GLH who were experiencing related abdominal pain or fullness. Technical success was recorded. Change in symptom severity, according to visual analog scale (VAS), was considered the primary outcome of the study. Volume change, based on the lesion volume at CT, and complications, based on the classification of the Society of Interventional Radiology, were regarded as secondary outcomes. The primary and secondary outcomes were recorded 6 and 12 months after the procedure. Comparison was performed by using the Wilcoxon signed-rank test or paired t test. Results Twenty-eight participants (mean age, 45 years ± 9; 25 women) were evaluated. Technical success was 100%. The mean VAS score was 8.3 before the procedure, which decreased to 1.4 (84.7% reduction) and 1.5 (83.5% reduction) at 6- and 12-month follow-ups, respectively (P < .001 for both). All participants reported relief of symptoms (17 of 28 participants [61%] with complete relief; 11 [39%] with partial relief) at 12-month follow-up. Mean GLH volumes dropped from 856.3 cm3 to 309.8 cm3 (65.7% reduction) and 206.0 cm3 (76% reduction) at 6- and 12-month follow-ups, respectively (P < .001 for both). No major complications were detected. Conclusion Percutaneous sclerotherapy is a safe and feasible method with promising results in the treatment of patients with symptomatic giant liver hemangioma. Clinical trial registration no. NCT03649113 © RSNA, 2021 See also the editorial by McGahan and Goldman in this issue.

Post-treatment persistent alpha-fetoprotein elevation in a patient with testicular cancer.

BACKGROUND: Persistent alpha-fetoprotein elevation in a patient following orchiectomy and chemotherapy for non-seminomatous testicular germ cell tumor is a rare condition when persistence of the tumor and false positivity of tumor marker elevation has to be differentiated. This situation often leads to over-treatment and potential toxicity with adverse events which can be severe. CASE: A case of a patient with the abovementioned disease and course of treatment is presented. As no radiological signs of the disease were present and the level of alpha-fetoprotein was mild and stable, the tumor marker elevation was evaluated as false positive. Possible causes of the tumor marker elevation were identified as other serious diseases are known to cause such a false positivity. The level of alpha-fetoprotein remained unchanged despite alcohol abstinence and hepatoprotective treatment by silymarin. Hepatitis B and C serological tests were negative, and no other malignant tumor was identified. Finding of terminal ileum circular wall thickening and stratification with a reaction of surrounding visceral fat and lymph nodes persisting in CT scans suggests the presence of inflammatory bowel disease, possibly explaining the alpha-fetoprotein elevation. The patient has no evidence of the disease more than 14 months after the end of chemotherapy treatment with no change in the elevation of alpha-fetoprotein. CONCLUSION: After the treatment, when no other indication of testicular cancer than an elevated alpha-fetoprotein level is present, the patient should be managed by ongoing surveillance.

Outcomes of older adults aged 90 and over with cutaneous malignancies after electrochemotherapy with bleomycin: A matched cohort analysis from the InspECT registry.

BACKGROUND: With extending life expectancy, more people are diagnosed with cutaneous malignancies at advanced ages and are offered nonsurgical treatment. We assessed outcomes of the oldest-old adults after electrochemotherapy (ECT). METHODS: The International Network for Sharing Practices of ECT (InspECT) registry was queried for adults aged ≥90 years (ys) with skin cancers/cutaneous metastases of any histotype who underwent bleomycin-ECT (2006-2019). These were subanalysed with patients aged <90 ys after matching 1:2 for tumor location, number, size, histotype, and previous treatments. We assessed ECT modalities, toxicity (CTCAE), response (RECIST), and patient perception (EQ-5D). RESULTS: Sixty-one patients represented the study cohort (median 92 ys, range 92-104), 122 the control group (median 77 ys, range 23-89). Among the oldest-old, 44 patients (72%) had primary/recurrent skin cancers, 17 (28%) cutaneous metastases. Median tumour size was 15 mm (range, 5-450). The oldest-old adults underwent ECT mainly under local/regional anaesthesia (59% vs 39% p = .012). We observed no differences regarding dose and route of chemotherapy (intravenous vs intratumoral, p = .308), electrode geometry (linear vs hexagonal, p = .172) and procedural duration (18 vs 21 min, p = .378). Complete response (57.4 [95%-CI 44.1%-70.0%] vs 64.7% [95%-CI 55.6%-73.2%], p = .222) and 1-year local control (76.7% vs 81.7, p = .092) rates were comparable. Pain and skin hyperpigmentation were mild in both groups. Skin ulceration persisted longer in the oldest-old patients (4.4 vs 2.4 months, p = .008). CONCLUSIONS: The oldest-old adults with cutaneous malignancies undergo ECT most commonly under local/regional anaesthesia with safety profiles and clinical effectiveness similar to their younger counterparts, except in case of ulcerated tumors.

Outcomes after up-front surgery and metronomic neoadjuvant chemotherapy with S-1 or UFT for early tongue squamous cell carcinoma.

BACKGROUND: Our aim was to investigate the disease-free survival in patients with tongue squamous cell carcinoma receiving metronomic neoadjuvant chemotherapy with 5-fluorouracil prodrugs (UFT or S-1) plus bleomycin compared with those who had up-front surgery retrospectively. METHODS: In this retrospective study, 108 patients with stages I to II tongue squamous cell carcinoma who had undergone surgery were divided into the "surgery group" or "neoadjuvant chemotherapy group." RESULTS: A total of 41 patients received up-front surgery; 67 received metronomic neoadjuvant chemotherapy with UFT plus bleomycin (39) or S-1 plus bleomycin (28). The rate of disease-free survival was the primary outcome measure. Neoadjuvant 5-fluorouracil prodrugs did not correlate higher with improved disease-free survival than up-front surgery (72 and 54%, respectively; hazard ratio for recurrence or death, 0.54; 95% confidence interval [CI], 0.28 to 1.03; P = 0.06). Patients who received S-1 were more likely than those who received UFT to have pathological complete response (46% vs. 15%; P = 0.007). Neoadjuvant S-1 significantly improved disease-free survival as compared with up-front surgery (79% vs. 54%; hazard ratio, 0.41; 95% CI, 0.15 to 0.98; P = 0.04). However, neoadjuvant UFT did not improve disease-free survival as compared with up-front surgery (67% vs. 54%, respectively; hazard ratio, 0.66; 95% CI, 0.31 to 1.33; P = 0.24). CONCLUSIONS: Neoadjuvant S-1 chemotherapy, as compared with up-front surgery, significantly improved disease-free survival among patients with tongue squamous cell carcinoma. CLINICAL RELEVANCE: A choice of drugs before neoadjuvant metronomic chemotherapy is needed.

Bleomycin sclerotherapy for eyelid venous malformations as an alternative to surgery or laser therapy.

PURPOSE: To evaluate the clinical outcome of patients with venous malformation (VM) involving the eyelid treated with bleomycin sclerotherapy. METHODS: A retrospective review was performed of 18 consecutive patients with VM involving the eyelid who underwent bleomycin sclerotherapy. Patients' clinical presentation, details of sclerotherapy, and post-sclerotherapy resolution of the lesion as well as any procedure-related complications were evaluated. RESULTS: Twelve women and six men of mean age 34.3±20.4 years underwent sclerotherapy with bleomycin. Chief complaints were cosmetic disfigurations with or without hemifacial deformity (n=2), pain in engorgement area (n=2), pain and swelling from venous thrombosis (n=2), swelling or engorgement obstructing their eyesight (n=2), or eyelid dysfunction (n=1). The lesions were only in the eyelid in three patients; otherwise they were extended out of the eyelid either superiorly (n=3), laterally (n=8), inferiorly (n=8), and/or posteriorly to the orbit (n=8) to various extents. Conjunctival involvement was present in 13 patients. 14 patients had received prior treatments including surgery, laser therapy, or non-bleomycin sclerotherapy. With an average three sessions of bleomycin sclerotherapy (average total dose 34.5 mg), more than 80% shrinkage was observed in seven patients (38.9%), 50-80% shrinkage in eight patients (44.4%), and 30-50% shrinkage in two patients (11.1%). One patient had recurrence, which was successfully treated again with bleomycin. No procedure-related complications were noted. CONCLUSIONS: The use of bleomycin appears to be a simple, safe, and effective treatment for venous malformations involving the eyelid, avoiding more elaborate and challenging surgical or laser interventions, and is even effective in full thickness lesions.

Cannabis Use and Bleomycin: An Overview and Case Study of Pulmonary Toxicity.

BACKGROUND: Legalization efforts in many states have heightened awareness of the medicinal uses of cannabis, and oncology nurses are more frequently caring for patients who have used or are using cannabis. Significant epidemiologic data on the prevalence of cannabis use in patients with cancer are not yet available, and not much is known about the effects of cannabis on cancer treatment. OBJECTIVES: This article describes the effects cannabis may have on the lungs, reviews indications for cannabis use in patients with cancer, and explores an atypical case of progressive pulmonary toxicity in a young patient with a history of Hodgkin lymphoma and cannabis use. METHODS: A review of the literature on cannabis-associated lung injury was conducted, with 32 articles selected for full review. FINDINGS: As cannabis use in cancer care continues to gain support, further research evaluating cannabis use in patients treated with bleomycin is warranted. In addition, the pros and cons of cannabis use must be fully evaluated and discussed with the patient with cancer prior to recommending its use.

Use of animal models in IPF research.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a poor prognosis and limited treatment options. Many compounds have shown efficacy in preclinical models of this condition, but only pirfenidone and nintedanib have been approved for clinical use. It is widely accepted that the current animal models of IPF need to be improved and in this review we have critically evaluated the current state of play of preclinical models of IPF and discuss the challenges facing this field. The popular model of a single intratracheal (I.T.) administration of bleomycin could be adapted to provide a more progressive fibrosis as is thought to occur in humans. Furthermore, currently the majority of new drugs are investigated in preclinical models of IPF are dosed using a prophylactic dosing regimen, whereas patients are almost always treated after the fibrosis is well established. Using a therapeutic dosing regimen in preclinical models would be a better way to establish potential efficacy of new drugs. The most popular endpoints examined in pre-clinical models of IPF are histological scoring and lung collagen content. However in IPF patients imaging and lung function tests are more commonly used as end points. We propose that examining more clinically relevant endpoints in pre-clinical models could also provide give a better indication of a compound's potential efficacy on endpoints measured in patients.

Transarterial Bleomycin-Lipiodol Embolization (B/LE) for Symptomatic Giant Hepatic Hemangioma.

BACKGROUND: Large hepatic hemangiomas can cause symptoms such as pain and bleeding. No consensus currently exists on the optimal management of large and symptomatic hemangiomas. The purpose of this study was to evaluate the role of transarterial bleomycin-lipiodol embolization (B/LE) in the treatment of symptomatic large hepatic hemangioma. MATERIALS AND METHODS: We retrospectively reviewed 23 patients (29 hemangiomas) treated between July 2011 and August 2017. Transarterial B/LE was performed using 7-15 cc of Lipiodol mixed with 30-45 IU of bleomycin by standard three-way stopcocks. All patients were followed clinically and by imaging for an average of 7.5 months. Patterns of bleomycin-lipiodol distribution in the periphery of hemangiomas were categorized into four different grades. Technical success was defined as proper delivery of bleomycin-lipiodol into the hemangioma confirmed by post-embolization computed tomography. Clinical success was defined as more than 50% reduction of hemangioma volume and symptom improvement during follow-ups. RESULTS: Technical success and clinical success were 100 and 73.9% (17 patients), respectively. Six patients (26.08%) experienced transient post-embolization syndrome. Significant size reduction was seen in patients with grade 4 hemangioma border coverage (P = 0.042). CONCLUSION: Transarterial B/LE is a safe and efficient alternative for controlling symptoms related to large hemangiomas.

Percutaneous Sclerotherapy for Giant Symptomatic Liver Hemangiomas: A Pilot Study.

This single-center prospective trial evaluated the safety and efficacy of percutaneous sclerotherapy for liver hemangiomas in 5 patients (1 man, 4 women; mean age 41.2 y) between 2016 and 2017. All patients were symptomatic (4 abdominal pain; 1 early satiety) and refused surgery. A single session of sclerotherapy with 20 cc mixture of 45 IU. Bleomycin in 10 cc distilled water and 10 cc Lipiodol (Ultra Fluide, Guerbet, France) was performed in all patients, achieving a 45.6%-71.1% lesion volume reduction and a 12.9%-41% reduction in the largest diameter of the lesion. Symptoms subsided in all patients during the 5-month follow-up period. Adverse events included a self-limited intraperitoneal hemorrhage in 1 patient.

Efectos del sistema endocannabinoide en el sistema respiratorio. Papel de los receptores TRPV1 en la fibrogénesis pulmonar / Endocannabinoid system effects on the respiratory system. The role of TRPV1 receptors in pulmonary fibrosis

Objetivos: establecer un modelo murino de fibrosis pulmonar inducida por bleomicina, investigando el posible papel protector del sistema endocannabinoide (SE) frente a la fibrosis. Métodos: se emplearon ratones salvajes (C5BL/6 y Balb/c) así como la cepa TRPV1-/-. Tras una única dosis intratraqueal de bleomicina, se analizó la respuesta fibrótica mediante un análisis histológico, la determinación de la expresión de marcadores del proceso profibrótico, el estudio de la actividad mieloperoxidasa y del contenido en hidroxiprolina del pulmón, así como el análisis de la expresión génica de VIP, PACAP, IL-1β, IL-6, TNF-α e IL-11, y el estado de activación de las rutas MAPKs (fosfo-JNK, fosfo-ERK) de la ruta de NF-κB (p-IκBα), la ruta de β-catenina y del TGFβ (GSK-3B), la activación de SMAD (pSMAD2) y pSTAT3, a nivel proteico. Resultados: la fibrosis pulmonar inducida por bleomicina en los ratones de la cepa TRPV- /- fue más severa que en la cepa salvaje C5BL/6. El contenido en hidroxiprolina y la actividad mieloperoxidasa fue mayor en los ratones TRPV1-/-. Se detectó un incremento significativo en la expresión génica de citoquinas proinflamatorias (TNF-a, IL-1b, IL11 e IL-6), pero no de VIP o PACAP, en la cepa TRPV1-/-. A nivel proteico, la expresión de pIKBα, pSTAT3, pSMAD2 y pJNK, pero no la de pERK, se vio incrementada en los ratones TRPV1-/-. Conclusiones: el modelo murino de fibrosis pulmonar inducida por bleomicina sigue siendo clave para continuar profundizando los conocimientos acerca de la patogénesis de la FPI. La modulación del SE podría tener un papel protector frente a la fibrosis pulmonar

Objectives: to establish a murine model of bleomycin-induced pulmonary fibrosis, analysing the possible protective role of the Endocannabinoid System (ES) against fibrosis. Methods: wild C5BL/6 and Balb/c mice, as well as the genetically modified strain TRPV1- /- were used. After a single dose of intratracheal bleomycin, the fibrotic response was analysed though histologic studies, the assessment of proinflammatory markers, myeloperoxidase activity, hydroxyproline content, genetic expression of VIP, PACAP, IL-1 β, IL-6, TNF-α and IL-11, as well as MAPK route (phospho-JNK, phospho-ERK), NF-κB (p-IκBα), β-cathenin, TGF-β (GSK-3B), SMAD (p-SMAD2) and pSTAT3, at a protein level. Results: pulmonary fibrosis was more severe in TRPV1-/- mice compared to C5BL/6 mice. A significant increase in proinflammatory markers such as TNF-α, IL-1β, IL11 and IL-6, but not VIP or PACAP, was observed. pIKBα, pSTAT3, pSMAD2 and pJNK, but not pERK, were increased at a protein level in TRPV-/- mice. Conclusions: the murine model of bleomycin-induced lung fibrosis remains a keystone to pioneer current investigation in lung fibrosis. Modulation of the ES might have a protective role

Actualización sobre el tratamiento de las verrugas vulgares en los niños / Treatment of Warts in Children: An Update

Las verrugas víricas son una de las infecciones cutáneas más frecuentes en los niños. Aunque existen múltiples opciones de tratamiento, no hay ningún tratamiento que garantice una total eficacia con una única sesión terapéutica. En la edad pediátrica el tratamiento es particularmente complicado, no solo porque algunos métodos son mal tolerados, sino también porque a menudo las expectativas de los padres respecto a la eficacia del tratamiento son poco realistas. Este artículo proporciona una actualización sobre las diferentes terapias antiverrugas, particularmente enfocado a los pacientes pediátricos, excluyendo el tratamiento de las verrugas de la mucosa oral y anogenital

Warts are among the most common skin infections in children. Although numerous treatment options are available, none are completely effective in a single session. Treatment is particularly complicated in children, not only because certain treatments are poorly tolerated, but also because parents frequently have unrealistic expectations. In this article, we offer an update on the treatments available for warts, focusing specifically on pediatric patients. We do not discuss treatments for oral and anogenital warts

Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect.

Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the importance of awareness and timely identification and management of this dermatological toxicity in patients undergoing bleomycin based combination chemotherapy.

Keloids and Hypertrophic Scars: A Spectrum of Clinical Challenges.

Since their earliest description, keloids and hypertrophic scars have beleaguered patients and clinicians alike. These scars can be aesthetically disfiguring, functionally debilitating, emotionally distressing, and psychologically damaging, culminating in a significant burden for patients. Our current understanding of keloid pathophysiology has grown and continues to advance while molecular biology, genetics, and technology provide ever-deepening insight into the nature of wound healing and the pathologic perturbations thereof. Greater understanding will lead to the development and application of refined therapeutic modalities. This article provides an overview of our current understanding of keloids, highlighting clinical characteristics and diagnostic criteria while providing a comprehensive summary of the many therapeutic modalities available. The proposed mechanism, application, adverse events, and reported efficacy of each modality is evaluated, and current recommendations are summarized.

Transcatheter Arterial Embolization Alone for Giant Hepatic Hemangioma.

Giant hepatic hemangioma is a benign liver condition that may be treated using surgery. We studied the digital subtraction angiographic (DSA) characteristics of giant hepatic hemangioma, and the effectiveness of transcatheter arterial embolization (TAE) alone for its treatment. This was a retrospective study of 27 patients diagnosed with giant hepatic hemangioma and treated with TAE alone (using lipiodol mixed with pingyangmycin) at the Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University, between January 2010 and March 2013. The feeding arteries were identified using DSA. All patients were followed up for between three weeks and 12 months. Changes in tumor diameter and symptoms were observed. The 27 patients included had giant hepatic hemangiomas ranging from 5.3 to 24.5 cm (mean, 11.24±5.08 cm) in the right (n = 13), left (n = 1) or both (n = 13) lobes. Preoperative hepatic angiography showed multiple abnormal vascular lakes in the early phase, known as the "early leaving but late returning, hanging nut on a twig" sign. On the day after TAE, hepatic transaminase levels were increased (ALT: 22.69±17.95 to 94.88±210.32 U/L; ALT: 24.00±12.37 to 99.70±211.54 U/L; both P<0.05), but not total bilirubin. Six patients complained of abdominal pain, and 12 experienced transient fever. In the months after TAE, tumor size decreased (baseline: 11.24±5.08; 3 months: 8.95±4.33; 6 months: 7.60±3.90 cm; P<0.05), and the patients' condition improved. These results indicated that TAE was effective and safe for treating giant hepatic hemangioma. TAE may be a useful alternative to surgery for the treatment of hepatic hemangioma.

[A clinical study on the treatment of mucocele by bleomyin A5 combined with phosphorus-32 colloid].

OBJECTIVE: To evaluate the effect of bleomyin A5 combined with phosphorus-32 colloid in the treatment of mucocele. METHODS: A total of 214 patients divided into three groups, bleomyin A5 (50 cases), phosphorus-32 colloid (50 cases) and bleomyin A5 combined with phosphorus-32 colloid (114 cases). RESULTS: The efficacy of bleomyin A5 group, phosphorus-32 colloid group, and bleomyin A5 combined with phosphorus-32 colloid group was 84% (42/50), 82% (41/50) and 98% (112/114), respectively. There were significant difference in efficacy among the three groups (P < 0.05). The phosphorus-32 colloid group and the bleomyin A5 group had no significant difference in efficacy (P > 0.05). CONCLUSIONS: The independent use of bleomyin A5 and phosphorus-32 colloid is effective, but the combined use of the two methods is more effective.

Renal impairment and late toxicity in germ-cell cancer survivors.

BACKGROUND: Treatment with bleomycin-etoposide-cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors. PATIENTS AND METHODS: BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow-up. The influence of BEP on GFR was evaluated with a linear mixed model. Risk factors for late toxicity were identified by a landmark analysis adjusting for covariates. The cohort was compared with the background population with standardized hospitalization/mortality rates. RESULTS: GFR changed (ΔGFR) -11.3%, -15.4% and -25.9% after three, four and five+ cycles of BEP. For patients with impaired renal function before treatment the changes were 4.3%, 0.0% and -12.8%, respectively. During follow-up a significant rebound of GFR was documented. Compared with the background population, all patients, irrespective of renal function, had an increased risk of CVD and death. This risk depended on chronic kidney disease stage before treatment but not after treatment. ΔGFR had no influence on risk of late toxicity [death: hazard ratio (HR) 1.06, P = 0.50; CVD: HR 0.97, P = 0.61]. CONCLUSIONS: Renal function after BEP is closely related to number of cycles, but the changes in GFR are partly reversible and have no impact on risk of CVD or death.