Trastuzumab (Herceptin)-associated lung injury

We report a case of trastuzumab pneumonitis in a patient with metastatic breast cancer. Bronchoalveolar lavage showed marked neutrophilia. A CT scan of the chest showed diffuse ground-glass opacities. The patient was treated with corticosteroids with a partial response. Trastuzumab-associated pneumonitis is not well described, and data in the literature is sparse. We describe the clinical and radiographical findings of trastuzumab-associated pneumonitis.     

老年肺癌放疗唤起性肺炎2例并文献复习

目的探讨老年人放疗唤起性肺炎的诊断和治疗。方法报告了2例老年肺癌患者放疗后应用靶向药物和抗生素治疗引起放疗唤起性肺炎的诊治过程。结果2例老年肺癌患者均接受放射治疗,在其后续治疗中发生放疗唤起性肺炎,诱导药物分别为厄洛替尼、左氧氟沙星和头孢哌酮舒巴坦。停用诱导药物和加用糖皮质激素治疗后,患者临床症状改善、肺部阴影吸收。结论放疗唤起性肺炎是一种罕见疾病,临床上容易误诊和漏诊,老年肺癌患者在接受放射治疗后的后续治疗中一定要警惕其发生。     

Transformation of NSCLC to SCLC after 1st- and 3rd-generation EGFR-TKI resistance and response to EP regimen and erlotinib: 2 CARE-compliant case reports

Rationale:Genotypic and histological evolution of non-small-cell lung cancer (NSCLC) into small-cell lung cancer (SCLC) has been described as a mechanism of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. However, the number of clinical cases is rare.Patient concerns:Two lung adenocarcinoma patients with EGFR mutations who recurred after radical resection transformed into SCLC under treatment with the sequential first- and third-generation EGFR-TKIs.Diagnosis:The 2 cases were both confirmed as SCLC by pathological rebiopsy after EGFR-TKIs resistance.Interventions:Case 1 was treated with etoposide plus cisplatin (EP) regimen and erlotinib, while case 2 was treated with erlotinib and EP followed by oral etoposide.Outcomes:Case 1 treated with EP only achieved 3-month progression-free survival (PFS), which is the first case that reported T790 M/C797S cis-mutation for osimertinib resistance before the SCLC transformation. However, case 2 treated with erlotinib and EP followed by oral etoposide, PFS lasted for 8 months.Lessons:The cases highlighted the importance of rebiopsy that identified pathologically SCLC transformation after EGFR-TKI resistance, and suggested the treatment of erlotinib plus EP followed by etoposide, which could provide a reference for such phenotype.     

Sulphasalazine-induced reversible hypersensitivity pneumonitis and fatal fibrosing alveolitis: report of two cases.

The cases of two patients with ulcerative colitis are described who developed pulmonary infiltrates during the early months of treatment with sulphasalazine. The first patient had a hypersensitivity pneumonitis, which was confirmed by challenge. Recovery was complete. The second patient developed a fibrosing alveolitis type reaction, with fatal outcome.     

厄洛替尼治疗晚期非小细胞肺癌36例临床观察

目的探讨厄洛替尼单药一线或二线治疗晚期非小细胞肺癌的疗效及不良反应。方法收集36例我科就诊的ⅢB期或者Ⅳ期非小细胞肺癌病例:所有患者均为病理学确诊,患者因体力状态较低一线选择厄洛替尼或至少接受1～2个周期化疗,治疗失败或因毒副反应不能耐受后二线选择口服厄洛替尼,具体用法:150 mg/qd,直至病情进展或者不能耐受副反应。结果在36例患者中,CR0例,PR 9例(25.0%),SD17例(45.2%),PD10例(27.8%),ORR为25.0%,DCR为72.2%。中位TTP为5.3个月,统计学结果显示:病理学类型与患者的DCR有关(P=0.029),腺癌的DCR较高。最常见的不良反应为皮疹及腹泻,经对症处理后可好转。结论厄洛替尼治疗晚期非小细胞肺癌疗效较好,不良反应较轻。     

Silicone Injection Causing Acute Pneumonitis: A Case Series

Local and systemic complications following injected silicone have been described, especially after cosmetic procedures by unlicensed practitioners. We report a retrospective case series of acute pneumonitis following silicone injection to the buttock. Medical records, pulmonary function tests, blood arterial gases, chest radiographs, and high-resolution computed tomography scans were reviewed. Five patients with acute pneumonitis after injected silicone were identified. All cases were men with a mean age was 25 years. Three patients had the procedure performed by the same practitioner. The amount of injected silicone ranged from 30 to 500 ml. The onset of clinical symptoms began as early as 24 h after injection to as late as 15 days. All cases had diffuse, peripheral, occasionally wedge-shaped opacities on high-resolution computed tomography. At presentation the mean oxygen saturation was 84%. All were treated with steroids and had clinical resolution of their illness within 1 month of presentation. Injection of silicone can lead to serious pulmonary complications but treatment with steroids seems to be beneficial.     

Acute pneumonitis consequent on pleurodesis with <Emphasis Type="Italic">Viscum album</Emphasis> extract: severe chest images but benign clinical course

Chemical pleurodesis is widely recommended in the treatment of pulmonary air leak of different etiologies as well as malignant pleural effusions and chylothorax. Conventional chemical pleurodesis using erythromycin, tetracycline, hydrophilic fumed silica, autologous blood and talc slurry has been standardized, and its complications, including high fever, intractable chest pain, and acute lung injury, seem to be frequent. Viscum album extract is a new chemical agent for pleurodesis, and only a few studies have reported outcomes of such chemical pleurodesis in the treatment of malignant pleural effusion. Moreover, the complications resulting from pleurodesis using Viscum album extract are very rare, and acute pneumonitis has not been reported. in this paper we report the first case of acute pneumonitis after pleurodesis using Viscum album extract in a 58-year-old man who had prolonged air leaks after a left upper lingularsegmentectomy for metastatic lung cancer. We performed repeated pleurodesis four times with 2 to 4 days intervals. While the patient had no symptoms of pneumonia, such as cough, sputum, chilling, and fatigue, a follow-up chest X-ray revealed increasing peribronchial consolidations and infiltrations in the left upper lobe. A chest tomography showed extensive parenchymal consolidations and ground-glass appearances in the left lungs, representing pneumonia with acute lung injury. The acute pneumonitis was spontaneously resolved with supportive care, and the patient was discharged ten days after the development of pneumonitis. We think that pleurodesis with Viscum album extract is effective, but repeated pleurodesis should be avoided for possible onset of acute pneumonitis.     

?Malignes“ ARDS

Acute respiratory failure and the “acute respiratory distress syndrome” (ARDS) are frequent medical conditions in critically ill patients. Various causes can potentially result in the development of ARDS. Two cases are presented, in which malignant diseases were identified as causes of the respiratory failure. The first patient was diagnosed with an acute myeloic leukemia M5 (FAB). In the second patient, lung histology revealed an adenocarcinoma of the lung. These case reports show that in addition to the classical causes of ARDS, specific disease entities can mimic this form of respiratory failure. Beside solid cancers and lymphomas, acute and progressive forms of inflammatory, parenchymal lung diseases (such as acute interstitial pneumonitis, acute eosinophilic pneumonia, diffuse alveolar hemorrhagia, and acute hypersensitivity pneumonitis) can manifest with this picture. As a consequence, the diagnostic workup of respiratory failure of unknown cause should include these entities.     

Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection

Patients with metastasized carcinoma of the pancreas have a very poor prognosis, and long-term survival cannot be expected. This case report describes two patients with an initial diagnosis of metastatic pancreatic cancer, both with hepatic metastases and one with an additional peritoneal carcinomatosis. Initially, both patients were treated intravenously with the FOLFIRINOX chemotherapy regimen, consisting of 5-FU, folinic acid, irinotecan and oxaliplatin. Surprisingly, the FOLFIRINOX treatment resulted in complete resolution of the hepatic metastases in both patients, with no lesions detectable by computed tomography scan. Furthermore, treatment response included decreased diameter of the primary tumor in the tail of the pancreas and disappearance of the additional peritoneal carcinomatosis. Both patients were discussed by our multidisciplinary tumor board, which recommended surgical resections of the carcinoma. The R0 resection of the primary tumor was successful in both cases and, interestingly, the resected tissues showed no evidence of the hepatic metastases intraoperatively. In the first case, the patient received a postoperative 6-mo course of adjuvant chemotherapy with gemcitabine. In the second case, the patient continued to receive the FOLFIRINOX regimen for an additional 6 mo postoperatively. At 12 mo after the operation, a nonresectable retroperitoneal lymph node metastasis was detected in the first patient, whereas the second patient remained in complete remission at the time of this report (5 mo after the adjuvant therapy was discontinued). This case report is the first of its kind to describe two cases of hepatic metastatic pancreatic carcinoma that were resectable following treatment with FOLFIRINOX. Further studies are required to examine the role of FOLFIRINOX as a neoadjuvant treatment option in subgroups of patients with initially metastasized pancreatic carcinoma.     

Two cases of amyopathic dermatomyositis with fatal rapidly progressive interstitial pneumonitis

Two middle-aged women showed typical erythematous heliotrope eruption and Gottron's sign without any symptom of myositis. The patients were diagnosed as 'amyopathic dermatomyositis' because of normal serum CPK levels, normal EMG and no histological abnormality by muscle biopsy. Clinical manifestations improved by the treatment with corticosteroids. During tapering of corticosteroids, however, intersititial pneumonitis developed and rapidly progressed. The first patients was treated with methylprednisolone pulse therapy, azathiopurine and methotrexate. The second patients was treated with betamethazone, methlprednisolone pulse therapy and cyclosporin A. In spite of these extensive immunosuppressive therapies, both patients died of pulmonary insufficiency a few months after admission. In the literature there has been only several cases of amyopathic dermatomyositis and only one case with fatal rapidly progressive interstitial pneumonitis. A new approach to the treatment of this disease should be made.     

Elliptocytosis and schistocytosis in myelodysplasia: report of two cases

Marked elliptocytosis and schistocytosis are described as unusual manifestations of haematopoietic dysplasia in two patients. The first patient, whose history was negative for inherited haemolytic anaemias, presented these prominent features on his first admission; 22 months later he developed an acute myeloblastic leukaemia. In the second patient, followed since 4 years for an autoimmune thrombocytopenic purpura, elliptocytosis and schistocytosis appeared 17 months before a pancytopenia established. The patient is now on follow-up and is treated for a refractory anaemia. In both cases bone marrow examinations revealed the typical criteria for myelodysplasia and this diagnosis was confirmed by cytogenetic analysis.     

Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis

Introduction: Although gefitinib used for the treatment of non‐small‐cell lung cancer is a well‐known cause of interstitial lung disease (ILD), few case reports on erlotinib‐induced ILD have been issued. The common risk factor of both of these two drug‐induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported. Methods: Report of a case. Results: We recently experienced a case of fatal erlotinib‐induced ILD, diagnosed based on clinical and radiologic findings, which occurred in a patient with radiation fibrosis. A 50‐year‐old male patient was started on erlotinib as a third‐line chemotherapy. Six days after taking erlotinib, a chest radiograph showed rapid progression of reticular infiltration in both lung fields. High‐resolution computed tomography scan findings were consistent with ILD, which was sufficient to diagnose as erlotinib‐induced ILD. The patient died of respiratory failure after 8 days of steroid infusion and erlotinib discontinuation. Conclusion: Our case shows a fatal side effect of erlotinib. This case had radiation fibrosis, so we suggest that radiation fibrosis may be another contributor of the occurrence of ILD in patients taking erlotinib. Please cite this paper as: Um S‐J, Lee S‐K, Yang DK, Son C, Roh MS, Kim KN, Lee K‐N and Choi PJ. Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis. The Clinical Respiratory Journal 2009; 3: 181–184.     

MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib

In human lung adenocarcinomas harboring EGFR mutations, a second-site point mutation that substitutes methionine for threonine at position 790 (T790M) is associated with approximately half of cases of acquired resistance to the EGFR kinase inhibitors, gefitinib and erlotinib. To identify other potential mechanisms that contribute to disease progression, we used array-based comparative genomic hybridization (aCGH) to compare genomic profiles of EGFR mutant tumors from untreated patients with those from patients with acquired resistance. Among three loci demonstrating recurrent copy number alterations (CNAs) specific to the acquired resistance set, one contained the MET proto-oncogene. Collectively, analysis of tumor samples from multiple independent patient cohorts revealed that MET was amplified in tumors from 9 of 43 (21%) patients with acquired resistance but in only two tumors from 62 untreated patients (3%) (P = 0.007, Fisher's Exact test). Among 10 resistant tumors from the nine patients with MET amplification, 4 also harbored the EGFR^T790M mutation. We also found that an existing EGFR mutant lung adenocarcinoma cell line, NCI-H820, harbors MET amplification in addition to a drug-sensitive EGFR mutation and the T790M change. Growth inhibition studies demonstrate that these cells are resistant to both erlotinib and an irreversible EGFR inhibitor (CL-387,785) but sensitive to a multikinase inhibitor (XL880) with potent activity against MET. Taken together, these data suggest that MET amplification occurs independently of EGFR^T790M mutations and that MET may be a clinically relevant therapeutic target for some patients with acquired resistance to gefitinib or erlotinib.     

Clinical efficacy of erlotinib in patients previously treated for advanced non-small cell lung cancer

Background and objective: Erlotinib is one of the standard second/third line treatments for patients with advanced non‐small cell lung cancer (NSCLC). This study investigated the efficacy of erlotinib in a Chinese population with advanced NSCLC and compared the predictive value of serum vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)‐α for the efficacy of erlotinib. Methods: Patients with advanced, previously treated NSCLC received 150 mg of erlotinib once daily orally until disease progression or intolerable toxicity. Serum levels of VEGF and TGF‐α were measured by ELISA at baseline and 1 month after treatment commenced. Results: There were 112 patients enrolled during the period October 2005 to February 2008 and followed until July 2008. Serum samples were available in 50 patients. Tumour response to erlotinib was partial in 35.7% of patients and 41.1% of patients had stable disease. The severity of skin rash (P < 0.001) had a significant positive correlation with the response to erlotinib. Median progression‐free survival (PFS) and overall survival were 6.3 months and 12.5 months, respectively. After erlotinib treatment, serum VEGF levels did not change significantly, while serum TGF‐α levels increased in patients who had partial response (P = 0.075) or stable disease (P = 0.055), but not in patients with progressive disease (P = 0.155). In patients with measurable serum TGF‐α levels at baseline the PFS and median survival were 5 and 9.9 months respectively, and in patients with no measurable TGF‐α at baseline the PFS and median survival were 11 and 21 months, respectively. Overall survival was significantly longer in patients with negative baseline serum TGF‐α (P = 0.002). Conclusions: Oral erlotinib was effective as a second/third line treatment for patients with advanced NSCLC. Baseline serum TGF‐α levels may be a predictor for the efficacy of erlotinib treatment.     

Successful reintroduction of methotrexate after acute pneumonitis in a patient with acute lymphoblastic leukemia

Low-dose methotrexate (MTX) is used as disease-modifying therapy in severe rheumatoid arthritis and as maintenance treatment in patients with complete remission of acute lymphoblastic leukemia (ALL). It is generally well tolerated, but in 27% of patients acute pneumonitis leads to discontinuation of treatment. We describe a 56-year-old female patient with newly diagnosed pre-B-ALL. She was treated with induction chemotherapy in July 1999 which lead to complete remission. Maintenance treatment with low-dose MTX and 6-mercaptopurine (6-MP) was started in December 1999. In April 2000 she was hospitalized because of fever, cough, and rapidly progressive dyspnea. No pathogens could be cultured from blood or bronchoalveolar lavage fluid. Computed tomography of the lungs revealed interstitial infiltration and ground-glass opacities. Acute pneumonitis was diagnosed, and MTX was stopped. Prednisone therapy lead to rapid clinical amelioration of dyspnea and hypoxemia. Since for this patient there was no alternative leukemia therapy, MTX was successfully reintroduced in August 2000 without reappearance of any respiratory symptoms. We discuss risk profile, clinical and histological presentation, and therapy of MTX-induced pneumonitis. To our knowledge, this is the first patient with ALL in whom successful reintroduction of MTX after severe pneumonitis has been reported.     

Two cases of malignant tumors of the inferior vena cava

The malignant tumors of the inferior vena cava are rare. Their prognosis is bad. We report two cases of a 17-year-old and 46-year-old woman presenting the one an intimal sarcoma of the inferior vena cava and the other a metastatic of adenocarcinoma whose primary tumor was not identified. The aortic wall was invaded in both patients. The ureter repulsed in first case, was invaded in second case. The treatment consisted on resection of the tumor including the aortic wall with vein closure in both patients, with right nephrectomy in second patient. In the two cases, a prosthetic reconstruction of the arterial integrity was attempted with aortobiiliac bypass. The two patients died after relapse tumorous to the 6th month in first patient and by multisystem organ failure 5th day post-operative in second. Through these two personal cases, we try to point out the difficult problem of diagnosis that put these tumors and their bad prognosis despite an improvement of treatment.     

Thyrotoxicosis revealing metastases of unrecognized thyroid cancer: a report on two cases

We report two cases of thyrotoxicosis-revealing functional metastases of a follicular carcinoma that extended to the bones, liver and kidneys in one case and to the lungs in the other. Both patients had undergone surgical intervention for a thyroid nodule more than 15 years before the diagnosis of thyrotoxicosis and metastatic dissemination. In both the cases, the carcinoma was not recognized by the pathologist after the first surgical intervention, but was finally diagnosed several years later due to the occurrence of thyrotoxicosis. Iodine-131 therapy was effective at suppressing the thyrotoxicosis in both the patients. The effectiveness on the metastatic extension was very different for each patient: in the first case, the patient died a few years later without any control of the metastatic tissue. For the second patient, the metastases disappeared a few months after radioiodine treatment, with the patient still in remission more than 10 years later. The physiopathology and the evolution of these two cases are discussed with the data available in the literature.     

Rituximab associated pneumonitis in antineutrophil cytoplasmic antibody-associated vasculitis

Rituximab is gaining use in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis. We report the first case of rituximab-induced pneumonitis in a patient with antineutrophil cytoplasmic antibody-associated vasculitis. Our patient with granulomatosis with polyangiitis (Wegener granulomatosis) had a relapse complicated by diffuse alveolar hemorrhage and acute kidney injury. His treatment included rituximab, steroids, cyclophosphamide, and plasmapheresis. Two weeks after his second dose of rituximab, he developed an acute deterioration in respiratory function. Rituximab-induced pneumonitis was diagnosed on a combination of computed tomography imaging, bronchoalveolar lavage, and negative tests for active vasculitis and infection. He was treated with a course of high-dose corticosteroids with improvement in respiratory function, computed tomography imaging of his chest, and inflammatory markers. Acute drug-induced pneumonitis is a rare but serious complication of rituximab. Distinguishing this complication from alveolar hemorrhage or pulmonary infection may be difficult. This diagnosis needs to be considered early in the right clinical context.     

Sorafenib-induced interstitial pneumonitis in a patient with hepatocellular carcinoma: a case report

Sorafenib is an oral multikinase inhibitor that has shown a survival benefit in patients with advanced hepatocellular carcinoma, and is considered to be generally safe. We treated a patient with interstitial lung disease that was associated with sorafenib therapy for the treatment of advanced hepatocellular carcinoma. A 74-year-old man with hepatitis-C-virus-related hepatocellular carcinoma was treated with sorafenib. After 8 days of sorafenib administration, he received radiation therapy for an intrahepatic tumor located in segment eight. On the 24th day of sorafenib treatment, the patient developed acute interstitial pneumonitis that rapidly improved after the discontinuation of sorafenib and treatment with high-dose steroids. This case alerts physicians to the possibility of sorafenib-induced interstitial lung disease.     

Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutation status

Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph⁺MPAL) is a rare type of acute leukemia having myeloid and lymphoid features. In the present study, we describe the successful treatment of a 71-year-old Japanese female patient with Ph⁺MPAL by the alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutations. The patient survived in her third complete remission (CR) for over 4 years. In her first CR, the patient was treated with multiple-agent chemotherapy and underwent maintenance therapy with imatinib and monthly vincristine and prednisolone (VP). At the first relapse, an examination of the bone marrow revealed a transformation into acute lymphoblastic leukemia and an F317L mutation in BCR-ABL1 gene, which responded preferentially to nilotinib over dasatinib. She achieved second CR, and nilotinib with VP therapy was selected for maintenance treatment. At second relapse, BCR-ABL1 mutational analysis revealed Y253H mutation instead of F317L mutation, resulting in resistance to nilotinib. The patient achieved third CR with dasatinib and VP therapy, and maintained CR with this treatment. This suggests that appropriate alternation of TKIs may contribute to long-term survival in elderly patients with Ph⁺MPAL.