Bleomycin-induced Pneumonitis Research Articles

Decade of insights: Bleomycin-induced pneumonitis and use of G-CSF in chemotherapy-treated germ cell testicular tumors and Hodgkin lymphoma—Real-world outcomes from an academic cancer center.

e17013 Background: Bleomycin induced pulmonary toxicity (BIP) occurs in 4-10% of treated patients. Preclinical reports suggest G-CSF use may increase BIP risk, due to neutrophil migration to lung tissues. Limited real-world clinical data is available and G-CSF use may reduce risk of treatment related toxicity with curative bleomycin combination treatment. Methods: We conducted a retrospective study of patients with GCT (Germ cell tumor) and HL (Hodgkin’s lymphoma) receiving bleomycin containing chemotherapy and at-least on dose of G-CSF at The James Cancer Center from 2010-2022 using the institutional database. BIP was diagnosed mainly using clinical symptoms complemented by radiological evidence when possible. We reviewed 361 patients, 145 in GCT group and 216 in HL group and clinically relevant information was recorded.Descriptive statistics for the study variables were presented using frequencies and percentages overall. The bivariate associations between G-CSF use and clinical outcomes were assessed using chi-square tests or fisher’s exact tests for the overall sample, and by chemotherapy type. We used SPSS 26.0 for all the statistical analyses, and an alpha level of 0.05 (two-sided) was used for all the tests. Results: Data on 361 patients, including 145 GCT and 216 HL patients treated with at least one dose of bleomycin was available. The median age was 36.3 years in the GCT group and 44.2 years in the HL group.144 patients in the GCT and 50 patients in the HL group received at least 1 dose of G-CSF. BIP occurred in 4.8% in the GCT and 7.4% of patients in the HL group. Only 2 out of 16 patients developing BIP in the HL group received G-CSF. All patients with BIP developed symptomatic disease. On bivariate analysis, no association was noted between BIP and G-CSF in either group (p-value =1.00 in GCT and p-value = 0.32 in HL). Febrile neutropenia (FN) was reported in 4 patients in the GCT group and 29 in the HL group. In the HL subgroup, 28 (28/29) patients developing FN did not receive G-CSF (p-value=0.0008). All patients who developed FN required hospital admission. Conclusions: Use of G-CSF in patients receiving bleomycin was not associated with an increased incidence of BIP. Incidence of FN was higher in patients not receiving G-CSF leading to hospital admissions. [Table: see text]

A Non-Coding Variant in LOC105371512 Confers Susceptibility to Bleomycin-Induced Lung Injury

Background: Bleomycin has been used as a cornerstone in the treatment of a variety of cancer types including Hodgkin Lymphoma (HL) and Germ Cell Tumor. Unfortunately, bleomycin has its complications, such as Bleomycin-induced pneumonitis (BIP) occurring in ~20% of patients and is fatal in 4-5%. In addition, there are no trials guiding effective treatment for BIP. While brentuximab as an alternative for bleomycin has shown good results in HL, it is still not considered as a standard first line treatment for most of the world. We aimed to investigate the significance of known genetic associations [(HFE rs1799945 (H63D) and BLMH rs1050565 (I443V)] in Asian patients, and identify previously uncharacterized genetic biomarkers associated with the predisposition to BIP. Through functional studies, we also sought to investigate the mechanisms in which these genetic biomarkers led to BIP. Methods: We analyzed 133 HL patients treated with bleomycin in Singapore. Clinical data was extracted from electronic medical records, BIP was characterized and graded by CTCAEv4. Genomic DNA was genotyped using Infinium Global Screening Array-24 v1.0 for 700,078 markers. Alt-R® CRISPR-Cas9 was used for the gene-editing experiment. Results: A total of 21.43% of patients developed clinically significant BIP, defined as CTCAEv4 ≥ Grade 2. Cumulative bleomycin dose was significantly lower in the BIP cases, as BIP patients had bleomycin discontinued from future therapy. All other clinical features were not significantly different between the groups. We replicated an association of HFE rs1799945 (H63D) with BIP and identified 4 new potential genetic predictors. LOC105371512 rs189773 was ranked the top loci. We genotyped 4 lung cancer cell lines. Comparing rs189773 CC and TT genotypes, CC had lower expression of pro-fibrotic markers, while higher expression of anti-fibrotic ones. We next used CRISPR/Cas9 to generate cells with either CC or TT genotype at rs189773 locus using the same cell line (A459). Interestingly, the BLMH protein expression level showed a reduction in A549(TT) compared to A549(CC), with a more remarkable effect in the presence of bleomycin. Screening the fibrotic biomarkers further revealed that growth factors and pro-fibrotic interleukins were up-regulated in A549(TT) compared to A549(CC) cells especially when the cells were treated with bleomycin. Next, we found that this SNP is located in a transcriptionally active region, with a higher activity level for the presence of T at the position compared to C. The rs189773-flanking region was subsequently shown to enhance the transcription level of distal genes with consistent effects on the profibrotic growth factors and cytokines. The qPCR study demonstrated that BLMH was not regulated at the mRNA level. We thus treated the cells with bleomycin and a 26S proteasome inhibitor, bortezomib. Interestingly, the bleomycin-induced down-regulation of BLMH protein was rescued upon co-treating the cells with both bleomycin and bortezomib. This proteasome inhibitor drug consistently diminished the heightened levels of profibrotic markers induced by bleomycin. Conclusion: In conclusion, in the first pharmacogenomics-GWAS study on BIP in Asians, rs189773 was ranked the top likely loci, with functional studies showing that this variant is in an enhancer region, modulating the cellular response to bleomycin via regulation of a distal locus, BLMH, and profibrotic growth factors. At the post-translational level, inhibition of the 26S proteasome by bortezomib restores BLMH expression and suppresses profibrotic growth factors. This study provides insights into future screening targets and potential new treatment options for BIP. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

SUCCESSFUL SALVAGE THERAPY OF BLEOMYCIN-INDUCED PNEUMONITIS WITH PIRFENIDONE

SUCCESSFUL SALVAGE THERAPY OF BLEOMYCIN-INDUCED PNEUMONITIS WITH PIRFENIDONE

A FATAL CASE OF ACCELERATED BLEOMYCIN-INDUCED PNEUMONITIS IN A PATIENT WITH STAGE IV NONSEMINOMATOUS GERM CELL TUMOR

A FATAL CASE OF ACCELERATED BLEOMYCIN-INDUCED PNEUMONITIS IN A PATIENT WITH STAGE IV NONSEMINOMATOUS GERM CELL TUMOR

High Doses of Kefir Accelerate Lung-Injury Progression in Bleomycin-Induced Pneumonitis in Rats

Background: Bleomycin-induced pneumonitis (BIP) is a common consequence of bleomycin (BLE) use during chemotherapy. Kefir is a probiotic with many health benefits. Many cancer patients in Indonesia consume kefir as a complementary traditional medicine alongside standard chemotherapy. Objectives: This study aimed to investigate the effects of high-dose kefir consumption on BIP in a rat model. Methods: Wistar male rats were given 0.3 mg of BLE via intranasal inhalation for 6 days with a daily intragastric administration of either phosphate buffered saline (PBS) or kefir at dosages of 2.5 mL, 3.5 mL, and 4.5 mL per day for 30 days. On day 30, lung sections were obtained and stained with hematoxylin and eosin for histological examinations. Immunohistochemistry tests were carried out to determine the activity levels of matrix metalloproteinase (MMP)-1, signal transducer, and activator of transcription (STAT)-3. TNF-α and IL-6 concentrations in plasma were also evaluated. Results: Histological results showed damage to the lung structure by inflammation with diffuse infiltrate, with some areas exhibiting slight fibrosis. The number of alveolar epithelial cells expressing MMP-1 significantly increased with the kefir dosage. Interestingly, only the highest dose of kefir raised IL-6 levels, while TNF-α levels increased at all kefir doses. STAT-3 showed a slight increase in activity level. As MMP-1 works to degrade fibrosis while both TNF-α and Il-6 are correlated with inflammation, these findings might explain the observed histological changes in lung structure in the BLE and kefir groups. Conclusions: The administration of high doses of kefir in rats increased the expression of pro-inflammatory cytokines, which worsened BIP.

Bleomycin-induced pulmonary toxicity in Hodgkin`s lymphoma patients

Bleomycin used as part of many chemo-therapeutic programs for treating Hodgkin lymphoma is associated with pulmonary toxicity. Development of complications after mediastinal radiotherapy is also well-known. However, the synergistic effect of the combination of radiotherapy and bleomycin is considered in the literature much less frequently and mainly when using the total focal doses (SOD) of 36 – 40 Gy. Since 1998 the chemo-radiotherapeutic regimens applied to the treatment of Hodgkin lymphoma in the MRRC (Obninsk) has involved subradical TTD of 20 – 30 Gy. The goal of the study is to evaluate pulmonary toxicity in Hodgkin lymphoma patients treated with chemo-radiotherapy involving ABVD and mediastinal treatment with TTD of 20 – 30 Gy.Methods. A series of 142 Hodgkin lymphoma patients received ABVD and mediastinal radiotherapy at the TTD 20 – 30 Gy. Conventional film and digital chest X-rays, linear and digital tomograms taken at different stages of treatment and follow up were analysed.Results. Changes in lungs in the form of a pathologic pulmonary pattern (interstitial pneumonitis) were seen in 39 (27.5%) of 142 patients. In 10 (25.6%) of 39 patients focal or confluent pneumonitis infiltration were found, that was 7% of the whole study group. Clinical evidence of bleomycin-induced pneumonitis was found in 6 (15.4%) of 39 patients. With follow-up terms up to 60 months fibrotic changes in lungs were absent. The occurrence of radiation pneumonitis was 17.6%, radiation fibrosis – 35.9%. Fibrotic changes were mainly grade 1 (94.1%). In HL patients with bleomycin-induced pneumonitis the occurrence of radiation pneumonitis was 43.6% (17 of 39 patients), radiation fibrosis – 58.9% (23 of 39 patients) while the corresponding figures for patients who did not have bleomycin-induced pneumonitis were 8.7% (9 of 103 patients) and 27.2% (28 of 103 patients), respectively (p < 0.001).Conclusion. A statistically significant increase in occurrence of radiation pneumonitis and radiation fibrosis was defined in HL patients who suffered bleomycin-induced pneumonitis.

Pharmacogenomic Prediction of Bleomycin-Induced Pneumonitis in South East Asian Hodgkin Lymphoma Patients

BackgroundHodgkin lymphoma (HL) accounts for 15% of all cancer diagnosis in young adults. Standard of care is ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine), which has resulted in overall cures of 70-90%. In the setting of HL, bleomycin is still one of the cornerstones in its treatment with the omission of bleomycin in the randomized trial of GHSG HD13 showing poorer outcomes. A major complication of HL treatment is Bleomycin induced pneumonitis (BIP) occurring in 0.4-28% of patients, with up to 10% mortality. Currently, we are unable to predict which patients are more prone. Given that human genomic variations underlie both disease susceptibility and drug response, uncovering genetic biomarkers predisposing to BIP is imperative to predicting and preventing BIP.MethodsIn this first pharmacogenomics study of BIP in South-East Asian patients, we perform both candidate gene and GWAS analyses. 96 HL patients were recruited from the National University Cancer Institute, Singapore (NCIS). BIP was clinically characterized and graded by CTCAEv4. Genetic association analysis was performed by regression (additive model) accounting for non-genetic predictor variables.ResultsAge at the start of bleomycin treatment, sex, genetic ancestry, concomitant chemotherapy treatment, treatment with G-CSF, stage of HL disease, pretreatment creatinine clearance, weight, chest irradiation and smoking history did not differ significantly between patients with and without BIP. The total number of treatment cycles (P=0.006) , cumulative exposure (P=0.01) and total exposure (P=0.028) were significantly lower in the BIP group as Bleomycin was omitted from further chemotherapy regimens once BIP was diagnosed.We independently replicated the association of HFE rs1799945 (H63D) with BIP (Cases: 15.38% vs Controls: 1.72%, P=0.0069, OR(95%CI)=2.89 (1.88-88.59)), while BLMH rs1050565 was not associated with BIP (P=0.92, OR(95%CI)=1.07 (0.29-3.93)). H63D carriers have 12.44 (1.98-78.17) times the odds of developing BIP compared to non-carriers (P=0.0088). We uncover a significant association of H63D with the severity of BIP (P=0.00087). HIST1H1T rs198846, a downstream variant in LD with H63D was also associated with BIP and its severity. H63D was predicted to be highly pathogenic (CADD Score=24.40) and at the top 1% of the most deleterious mutations in the human genome.The GWAS uncovered 4 novel genetic biomarkers with suggestive evidence of association with BIP (Unknown locus on Chr 17, MRC2 rs8072984, TMEM260 rs1124062 and KIF26B rs12747330). MRC2 rs8072984 is involved with remodeling of extracellular matrix, and defects in this could cause poor lung remodeling after bleomycin insult. TMEM260 rs1124062 and KIF26B rs12747330 are both involved with renal anomalies and development suggesting that defects in these could affect bleomycin clearance.ConclusionThis is the first pharmacogenomics study of BIP in South East Asian patients, looking at both candidate gene and GWAS analyses. Our results suggest that iron regulation could be the driver in the etiopathogenesis of BIP, supporting the utility of H63D testing in the risk stratification of patients receiving Bleomycin. Moreover, GWAS analyses have discovered 4 novel markers that suggest an association with BIP, which will be further evaluated and should be independently replicated in a larger cohort. DisclosuresChng:Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Merck: Research Funding; Amgen: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Aslan: Research Funding.

Spontaneous Pneumomediastinum and Bilateral Pneumothoraces in a Patient with Bleomycin-Induced Pneumonitis.

Bleomycin lung toxicity is well established and can manifest as bleomycin-induced pneumonitis, but pneumomediastinum and pneumothorax are very rare complications. We report the case of a 73-year-old woman, recently treated with bleomycin for Hodgkin’s disease, who was admitted for bleomycin-induced pneumonitis. Two weeks later she had a pneumomediastinum with extensive subcutaneous emphysema and small bilateral pneumothoraces. Three months after that she was readmitted for dyspnoea. The CT scan showed complete regression of the pneumomediastinum but extensive bilateral ground-glass infiltrates. The patient died from respiratory failure 2 weeks later.LEARNING POINTSRespiratory investigation before initiation of bleomycin treatment and then close follow-up during treatment of any abnormalities found is mandatory, as bleomycin -induced toxicity can lead to fibrosis and secondary pneumothorax/pneumomediastinum with high morbidity/mortality.Bleomycin-induce pneumonitis (BIP) is managed with bleomycin discontinuation (Grade 1A) and system corticosteroid (Grade 1B).Supplemental oxygen is discouraged for BIP, but indicated for conservative management of pneumothoraces, so this case was managed with limited oxygen supplementation (aiming for oxygen saturation of 92–94%).

Impact of Granulocyte-colony Stimulating Factor on Bleomycin-induced Pneumonitis in Chemotherapy-treated Germ Cell Tumors.

To examine the impact of granulocyte-colony stimulating factor (G-CSF) use on the incidence and severity of bleomycin-induced pneumonitis (BIP) in patients with germ cell tumor (GCT) receiving first-line chemotherapy. Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy, and medical records. All patients receiving first line chemotherapy between January 1, 2000 and December 31, 2010 were included. Patients receiving at least 1 dose of G-CSF were identified. BIP was graded using Common Terminology Criteria for Adverse Events criteria. Logistic regression was used to explore predictors for risk and severity of BIP. Statistical significance was defined as P< .05. Data on 212 patients with GCT treated with a bleomycin-containing chemotherapy regimen were available. The median age was 31 years. The median follow-up period was 36.7 months. BIP occurred in 73 patients (34%), a majority (n= 55) of which were asymptomatic events (Common Terminology Criteria for Adverse Events, grade 1). G-CSF use was not associated with increased risk of BIP in multivariable analyses (odds ratio, 1.60; P= .13), nor was it associated with increased severity of symptomatic BIP (on average 1.22 grades higher; P= .09). There was a non-statistically significant trend towards greater risk of BIP in patients that developed renal impairment during chemotherapy treatment (odds ratio, 2.56; P= .053). In patients with GCT receiving first line chemotherapy, G-CSF use is not associated with an increased risk of BIP. Furthermore, the use of G-CSF did not have any significant effect on the severity of BIP events. Clinicians are reminded to be vigilant of patients that develop renal impairment while undergoing chemotherapy treatment, given the greater risk of BIP.

Bleomycin-Induced Pneumonitis in a 16-Year-Old Girl With Hodgkin Lymphoma and No Risk Factors: Complete Reversibility With Steroids

Bleomycin-Induced Pneumonitis in a 16-Year-Old Girl With Hodgkin Lymphoma and No Risk Factors: Complete Reversibility With Steroids

Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin

For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors. All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured the diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1 second, and forced vital capacity were performed systematically before, during, and after treatment with BEP for 5 years of follow-up. According to local protocol, bleomycin was discontinued if hemoglobin-corrected DLCO (DLCOc) decreased ≥ 25% compared with pretreatment value. Covariates of possible importance were evaluated with a multiple regression analysis for pretreatment PFTs and with a mixed model for follow-up PFTs. Bleomycin was adjusted on the basis of PFT results and was thus omitted as covariate. Overall, 565 patients were evaluated with a PFT before or after treatment with BEP. During BEP, 15 patients died of progressive disease or toxicity, including one patient from bleomycin-induced pneumonitis. Post-treatment DLCOc decreased significantly, with a rebound during follow-up. Forced expiratory volume in 1 second and forced vital capacity remained unchanged after BEP but increased significantly to levels above pretreatment during follow-up. International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group, mediastinal primary, pulmonary metastases, and smoking all significantly influenced baseline PFT results. Pulmonary surgery, pulmonary embolism, IGCCCG poor prognosis, and smoking influenced PFT during follow-up. Mediastinal primary, pulmonary metastases, age, or doses of cisplatin and etoposide had no influence on follow-up PFT, and renal function did not influence PFT. After 5 years of follow-up, pulmonary impairment in patients with germ cell cancer who were treated with BEP was limited. Exceptions were patients treated with pulmonary surgery, those who suffered pulmonary embolism, and those in the IGCCCG poor prognostic group.

Stanniocalcin-1 inhibits thrombin-induced signaling and protects from bleomycin-induced lung injury.

Thrombin-induced and proteinase-activated receptor 1 (PAR1)-mediated signaling increases ROS production, activates ERK, and promotes inflammation and fibroblast proliferation in bleomycin-induced lung injury. Stanniocalcin-1 (STC1) activates anti-oxidant pathways, inhibits inflammation and provides cytoprotection; hence, we hypothesized that STC1 will inhibit thrombin/PAR1 signaling and protect from bleomycin-induced pneumonitis. We determined thrombin level and activity, thrombin-induced PAR-1-mediated signaling, superoxide generation and lung pathology after intra-tracheal administration of bleomycin to WT and STC1 Tg mice. Lungs of bleomycin-treated WT mice display: severe pneumonitis; increased generation of superoxide; vascular leak; increased thrombin protein abundance and activity; activation of ERK; greater cytokine/chemokine release and infiltration with T-cells and macrophages. Lungs of STC1 Tg mice displayed none of the above changes. Mechanistic analysis in cultured pulmonary epithelial cells (A549) suggests that STC1 inhibits thrombin-induced and PAR1-mediated ERK activation through suppression of superoxide. In conclusion, STC1 blunts bleomycin-induced rise in thrombin protein and activity, diminishes thrombin-induced signaling through PAR1 to ERK, and inhibits bleomycin-induced pneumonitis. Moreover, our study identifies a new set of cytokines/chemokines, which play a role in the pathogenesis of bleomycin-induced lung injury. These findings broaden the array of potential therapeutic targets for the treatment of lung diseases characterized by thrombin activation, oxidant stress and inflammation.

Bleomycin-Induced Pneumonitis in the Treatment of Ovarian Sex Cord-Stromal Tumors: A Systematic Review and Meta-analysis.

Adult ovarian sex cord-stromal tumors (SCSTs) are a rare histological subtype of ovarian cancer associated with a favorable prognosis. Bleomycin-containing regimens are standards of care, although pneumonitis may cause potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of bleomycin in SCST treatment. We performed a systematic literature review of all studies of bleomycin therapy for SCSTs that were referenced in MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials and published from 1986 to 2014. Eight studies totaling 221 patients were included. Rates of pneumonitis (7.7%; 95% confidence interval, 4.2-11.2) and mortality (1.8%; 95% confidence interval, 0.1-3.6) related to bleomycin were significant. However, these results were very similar to those reported for men who were treated with bleomycin for a male germ cell tumor, suggesting that women with ovarian SCSTs are not particularly vulnerable to bleomycin lung toxicity. The main risk factors of bleomycin-induced pneumonitis are high cumulative bleomycin dose (>400 U or mg), age older than 40 years, and impaired renal function. Whether granulocyte colony-stimulating factor is a risk factor remains controversial. Bleomycin-induced pneumonitis frequently occurs in patients with SCSTs and lacks effective treatment. Prevention lies in limiting cumulative bleomycin dose, monitoring pulmonary function during treatment, discontinuing bleomycin at the onset of pulmonary symptoms or if pulmonary function is impaired, and avoiding bleomycin in older patients.

Bleomycin-induced pulmonary changes on restaging CT scans: Frequency and correlation with fibrosis markers.

4540 Background: Bleomycin-induced pneumonitis (BIP) is a well-known, potentially fatal, side-effect in metastatic testicular cancer (mTC). We prospectively investigated I: prevalence of lesions su...

Older patients and risk of developing and dying from bleomycin-induced lung toxicity.

8584 Background: Bleomycin-induced pneumonitis (BIP) has been well described in classical Hodgkin lymphoma (cHL) patients treated with bleomycin-containing chemotherapy regimens. The incidence of acute and subacute pulmonary toxicity varies widely and multiple factors contribute to mortality in patients with BIP. We therefore reviewed the outcome of cHL patients treated at a single institution to further define the incidence of BIP and to identify major contributors to BIP-associated morbidity and mortality. Methods: One hundred sixty-one pediatric and adult patients who were treated with bleomycin-containing chemotherapy for newly diagnosed cHL between January 2000 and December 2012 were eligible for this retrospective review. BIP was defined by fever, pulmonary symptoms, pulmonary infiltrates, or a decline in DLCO, with no evidence of an infectious etiology. Results: BIP was observed in 43.5 % (n=70) of patients. Age >/=45 years was associated with both an increased incidence (p= <0.0001) and increased severity (p=0.0005) of lung toxicity. ABVD regimen as initial therapy (p= <0.001), obesity (p=0.0331) and the presence of at least one cardiac or respiratory comorbidity (p=0.0088) was also associated with the development of BIP. Higher BMI was associated with earlier onset of lung toxicity. No significant increase in pulmonary toxicity was noted with co-administration of G-CSF (p=0.7249). Bleomycin related mortality rate was 4.97 % (n=8) when all patients were considered and 11.43 % (8/70) in patients who developed pulmonary symptoms. Seventy five percent (6/8) of those who died were older than 60 years. Conclusions: The risk of BIP is significant in cHL with the use of bleomycin-containing regimens. Age >/= 45 years appears to increase the risk of BIP and is associated with increased mortality. These findings highlight the need for testing novel treatment combinations in cHL patients that omit bleomycin.

Primary testicular carcinoid tumour with mature teratoma in undescended testis metastatic to lymph nodes.

We report a case of primary testicular carcinoid tumour with mature teratoma metastatic to the para-aortic lymph node and the lymph node around the left gonadal vein, which was treated with radical orchiectomy, bleomycin, etoposide, and cisplatin chemotherapy, and modified retroperitoneal lymph node dissection. Three days after modified retroperitoneal lymph node dissection, bleomycin induced pneumonitis occurred, which was resolved with steroid administration. The patient is alive without recurrence 31 months after radical orchiectomy.

FELD better not thinking of metastases only when liver lesions appear after bleomycin-based treatment for non-seminoma testis from metastases

BackgroundBleomycin has become an integral part of chemotherapy in patients with germ-cell tumors. One of the most feared side effects is bleomycin-induced pneumonitis. In patients with mild or moderate BIP, radiological signs disappear almost completely within nine months after discontinuation of bleomycin treatment.Case presentationWe present a patient with a history of non seminoma of the testis and bleomycin-induced pneumonitis. During follow-up, regression of the hypothesis of eosinophilic migration to the liver after regression of bleomycin-induced pneumonitis is highly suspicious based on transient eosinophilia and focal eosinophilic liver disease.ConclusionAs follow up may consist of CT scanning in germ-line tumor patients, transient eosinophilic liver lesions reported during regressive bleomycin-induced pneumonitis should not be presumed automatically as metastatic tumor relapse and require further sequential imaging and pathological examination.

Bleomycin-Induced Lung Injury

Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and Hodgkin’s lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. The mechanism of bleomycin-induced pneumonitis (BIP) involves oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and the elaboration of inflammatory cytokines. Ultimately, BIP can progress to lung fibrosis. The diagnosis of BIP is established by the combination of systemic symptoms, radiological and histological findings, and respiratory function tests abnormalities, while other disorders should be excluded. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. In general, the clinical picture is extremely complex. A greater understanding of the BIP pathogenesis may lead to the development of new agents capable of preventing or even treating the injury already present. Physicians who prescribe bleomycin must be aware of the potential pulmonary toxicity, especially in the presence of risk factors. This review will focus on BIP, mainly regarding recent advances and perspectives in diagnosis and treatment.

Pneumomediastinum, subcutaneous emphysema, and pneumothorax after a pulmonary function testing in a patient with bleomycin-induced interstitial pneumonitis

Spontaneous pneumomediastinum is an uncommon event, the clinical picture of which includes retrosternal chest pain, subcutaneous emphysema, dyspnea, and dysphonia. The pathophysiological mechanism involved is the emergence of a pressure gradient between the alveoli and surrounding structures, causing alveolar rupture with subsequent dissection of the peribronchovascular sheath and infiltration of the mediastinum and subcutaneous tissue with air. Known triggers include acute exacerbations of asthma and situations that require the Valsalva maneuver. We described and documented with HRCT scans the occurrence of pneumomediastinum after a patient with bleomycin-induced interstitial lung disease underwent pulmonary function testing. Although uncommon, the association between pulmonary function testing and air leak syndromes has been increasingly reported in the literature, and lung diseases, such as interstitial lung diseases, include structural changes that facilitate the occurrence of this complication.

Bilateral Laparoscopic Postchemotherapy Retroperitoneal Lymph-Node Dissection in Nonseminomatous Germ Cell Tumors–a Comparison to Template Dissection

Retroperitoneal lymph node dissection (RPLND) is performed in patients with advanced nonseminomatous (NSGCT) germ cell tumors and residual retroperitoneal mass post-chemotherapy. The extent of node dissection remains unclear. Ipsilateral template dissection is a compromise between morbidity and oncological efficacy. Here, we compare ipsilateral with primary bilateral laparoscopic (L)-RPLND after chemotherapy in terms of morbidity and oncological safety. Nineteen laparoscopic ipsilateral L-RPLNDs (Group A) after platinum-based chemotherapy in patients with clinical stage IIA-III NSGCT were performed, while 20 patients underwent primary bilateral L-RPLND (Group B). We included patients with residuals localized in the retroperitoneum >1 cm and a tumor marker negativity after chemotherapy. The patients in group B had nerve sparing based on their respective tumor volume. All L-RPLND was successfully finished without conversion. Mean operative time in group A was 221 minutes and 270 minutes in group B (p=0.12). There were no deviations from the normal postoperative course in 36 cases. There was one Grade II complication (bleomycin-induced pneumonitis) in group A and 1 grade III complication (chylous ascites) in group B. The mean hospitalization time in both groups was 5 days (p=0.1). With regard to the overall rate of disease recurrence, no significant difference was found between both groups (HR=1.84; 95% CI 0.17-39.92; p=0.6109). Postchemotherapy L-RPLND remains technically challenging. However, the morbidity of primary bilateral post-chemotherapy L-RPLND is similar to that of template dissection. Additional oncological safety is provided, which is particularly relevant in patients with more extensive retroperitoneal tumor volume.