Familial occurrence of bronchiolitis obliterans associated with pulmonary aspergillosis

We report the familial occurrence of bronchiolitis obliterans (BO) associated with pulmonary aspergillosis. A mother and daughter admitted for dyspnea after taking Sauropus androgynus both had overfiltration of both lungs in chest X-ray and severe obstructive impairment in lung function tests. They were initially diagnosed with severe asthma and treated with high-dose prednisolone (0.5mg/kg/day) for 1 month to no effects. They did not show reversibility in lung function test. They were difinitively diagnosed with BO associated with Sauropus androgynus. Six months later, the mother's symptoms worsened with productive sputum and severe dyspnea, and her chest X-ray showed patty shadow in both upper lung fields. Precipitating antibodies to aspergillus antigen were positive and aspergillus fumigatus was detected from her sputum culture. She was diagnosed with aspergillosis and treatment with Micafungin (MCFG) and Itraconazole (ITCZ) was started. The daughter's symptoms also worsened and her chest tomography showed multiple cavities in both lung fields. Precipitating antibodies to aspergillus were positive. She was diagnosed with Invasive aspergillosis. She was treated unsuccessfully with MCFG and Amphotericin B (AMPH) and ITCZ. Few reports cover BO with aspergillus infection without organ impairment. In these 2 cases, treatment with steroids' or immune suppression of the lung with BO may a trigger aspergillus infection.     

Pneumococcal Pneumonia Co-infection with Mycobacterium avium and Nocardia cyriacigeorgica in an Immunocompetent Patient

A 61-year-old woman was transferred with a complaint of a fever and productive cough. She had tested positive for Mycobacterium avium and Nocardia cyriacigeorgica at least twice, and Streptococcus pneumonia (PISP) was isolated (3+) from her purulent sputum. As radiological findings, a lower lung field-dominant infiltration shadow and nodular shadow with cavity were recognized in the bilateral lung fields. We diagnosed her with pneumococcal pneumonia co-infection with M. avium and N. cyriacigeorgica. She was treated with MEPM for pneumococcal pneumonia, a standard regimen containing clarithromycin for pulmonary M. avium complex (MAC) disease, and sulfamethoxazole/trimethoprim for pulmonary nocardiosis. She improved with appropriate treatment.     

A case of Pneumocystis carinii pneumonia with hyperinfection of Strongyloides stercoralis complicated with smoldering adult T-cell leukemia

A 43-year-old woman visited a clinic for an attack of bronchial asthma which she had been suffering since her childhood. She was treated with prednisolone which was used for the first time. Two weeks later, she had a fever and her chest X-ray showed diffuse reticulonodular shadows on both middle to lower lung fields. In spite of the use of antibacterial drugs, her symptoms such as cough, dyspnea, malaise and fever increased. It was revealed that she had Stronglyoides sterocoralis in the stool. She was referred to our department for treatment and further examination. Transbronchial lung biopsy (TBLB) was performed, and cyst of Pneumocystis carinii were histologically detected in the lung specimen. Anti-human T-lymphotropic virus type 1 (HTLV-1) antibody in the serum was 1:4,096 less than. Typical adult T-cell leukemia (ATL) cells were also observed in the peripheral blood smear at the rate of 10-15% of leukocytes. The parasite was observed in the sputum too. We diagnosed her as having Pneumocystis carinii pneumonia with hyperinfection of Strongyloides stercoralis complicated with smoldering ATL, and the pneumonia might have been induced by steroid therapy (total doses of 500 mg, for 25 days). After sulfamethoxazole-trimethoprim (ST compound) was used for the Pneumocystis carinii pneumonia, her symptoms markedly subsided, and the chest X-ray findings turned to normal by 45 days after the treatment. Thiabendazole was initially administered for the Strongyloidiasis and the parasite temporarily disappeared from both sputum and stool. Then pyrvinium pamoate and mebendazole were used, but the parasite could not be completely eradicated in the stool. We did not treat the smoldering ATL because there were no symptoms. We have been looking after her as an outpatient now, and she has neither symptoms nor signs.     

High dose ara-C therapy induced bradycardia in an acute myeloid leukemia patient with inv (16)(p13q22)

A 20-year-old Japanese woman was diagnosed as having acute myeloid leukemia with inv(16)(p13 q22). She achieved complete remission (CR) after treatment with a standard dose of cytarabine(ara-C) and idarubicin. She received high dose ara-C and etoposide for the 2nd consolidation chemotherapy. On the 5th fraction of high dose ara-C, her heart rate dropped to 52/minute and returned to 72/minute after the cessation of ara-C. After achieving informed consent, we gave her another course of high dose ara-C, which once again resulted in a decreased heart rate. This suggests that the administration of high dose ara-C could cause bradycardia.     

Two lung adenocarcinoma patients with multiple brain metastasis treated with Gefitinib and surviving more than 2 years]

Case 1 is a 78-year-old woman in whom lung adenocarcinoma with multiple brain metastasis (cT2N3M1, stage IV) was diagnosed. She was treated with Gefitinib alone. Her lung tumor and metastatic brain lesions decreased 6 months after the start of therapy. She has no recurrence and is still alive with a good performance status after 25 months. Case 2 is an 80-year-old woman in whom lung adenocarcinoma with multiple brain (cT2N3M1, stage IV) was diagnosed. She was also treated with Gefitinib alone and her lung tumor and metastatic brain becomes improved 6 months after the start of therapy. She maintained a good performance status for more than 2 years (29 months). However, 29 months after beginning treatment, she had recurrence in bone and died 2 months later, 31 months after the start of therapy. The prognosis of non-small cell lung cancer with multiple brain metastasis is very poor and the efficacy of chemotherapy for the treatment of multiple brain metastases is limited, and longterm survival remains disappointing. We report two lung adenocarcinoma patients with multiple brain metastasis who survived more than 2 years by treatment with Gefitinib alone.     

A myelo dysplastic syndrome (refractory anemia with excess of blasts) occurred in a patient with small cell lung cancer during complete response

A myelo dysplastic syndrome (MDS), refractory anemia with excess of blasts (RAEB), that occurred in a patient with small cell lung cancer (SCLC) during a period of complete response (CR) was reported. A 66-year-old female patient was diagnosed as SCLC in March, 1985. Induction chemotherapy (CDDP, ADM, VCR, VP-16) achieved CR in May, 1985. She had received maintenance chemotherapy (CDDP, ADM, VCR (or VDS), VP-16) and chest irradiation (48.6 Gy) until May, 1988. The hematologic findings revealed MDS and she was admitted in June, 1989. She died one month after onset of MDS because of pneumonia. An autopsy showed no evidence of recurrence of small cell carcinoma in the primary site and other organs. There is a possibility of the risk of secondary leukemia following long term chemotherapy and irradiation in patients with SCLC, and the role of treatment after the achievement of CR in patients with SCLC remains to be clarified.     

A case of volcanic ash lung: report of a case]

A 57-year-old woman inhaled much volcanic ash without using a mask every day during the eruption of the Miyake Volcano in August 2000. An abnormal shadow was pointed out on her chest radiography by chance, after she sought refuge in Higashimurayama city in September. She had no respiratory symptoms and her chest radiography in an annual health check in July 2000 had showed no abnormality. She was admitted to our hospital and thoracoscopic lung biopsy was performed. We diagnosed it as lung inflammation caused by volcanic ash. The reasons for diagnosis were because the abnormal shadow appeared after the inhalation of volcanic ash, chest computed tomography showed diffuse irregular shadows with air bronchogram, thoracoscopic lung biopsy showed cellular-bronchiolitis around crystals, and the results of mineralogical analysis of the particles in alveolar macrophages detected in the biopsy specimen by scanning electron microscopy (SEM) were very similar to those of volcanic ash. The shadow on her chest radiography disappeared gradually without any treatment, but she avoided further exposure to volcanic ash. It is necessary to consider volcanic ash capable of causing lung inflammation.     

A case of bronchiolitis obliterans syndrome successfully treated by Tiotropium bromide]

A 48-year-old woman was admitted with dyspnea on effort. She suffered from adult T-cell leukemia and received peripheral blood stem cell transplantation (PBSCT). Eight months after the PBSCT, she developed dyspnea on effort and was treated with bronchodilator, inhaled corticosteroid, anti-leukotriene drug, theophylline and oxytropium bromide. However her symptoms progressed and she was admitted. We diagnosed bronchiolitis obliterans syndrome (BOS) because of obstructive pulmonary dysfunction, diffuse patchy high density of the lung field on chest computed tomography and decreased ventilation with peripheral patchy accumulation on ventilation scintigraphy. She was treated with corticosteroid and cyclosporine A and her symptoms and her pulmonary function were improved. However, in parallel with corticosteroid tapering, her symptoms and pulmonary functions worsened. Treatment with Tiotropium bromide was started and her pulmonary function improved significantly. Her pulmonary function did not worsen and tapering steroid dose was successfully achieved. PBSCT was reported to up-regulate the muscarinic receptor activity in lung. Tiotropium bromide might become one additional option for the treatment of BOS.     

A case of long-term survival of a patient with complicated diffuse metastatic leptomeningeal carcinomatosis secondary to lung adenocarcinoma

A case of long-term survival of a female patient with complicated diffuse metastatic leptomeningeal carcinomatosis (DMLC) secondary to lung cancer is reported. A 36-year-old woman, hospitalized with a chief complaint of headache and unproductive cough, was diagnosed as having primary lung adenocarcinoma (T4N1M1 oss) and was given systemic chemotherapy. Although progressive deterioration of her headache continued, repeated neurological examination, cerebrospinal fluid (CSF) examination, and cranial CT scans failed to show evidence of metastasis to the central nervous system, and the only finding suggesting CNS involvement was an elevated CEA level in CSF. Later in the course of her treatment, the patient suddenly lost her vision and subsequently consciousness due to acute increased intracranial pressure, and emergency ventricular drainage was performed for therapeutic and diagnostic purposes. Malignant cells were found in CSF obtained from a ventricular drainage and she was treated successfully by systemic and intrathecal chemotherapeutic agents. She was discharged after a ventriculoperitoneal shunt operation for hydrocephalus; a double-dome reservoir was used for continuous intrathecal administration of the anticancer drugs, and a shunt filter was located in the tube to prevent the dissemination of cancer cells. In addition to methotrexate and cytosine arabinoside, ACNU and interleukin-2 were administered intrathecally without serious adverse effects, but no apparent therapeutic effects were noted either. She survived over 2 years after DMLC was first diagnosed. At autopsy DMLC secondary to lung adenocarcinoma was confirmed, but no evidence of leukoencephalopathy due to aggressive intrathecal chemotherapy was found. Current therapy for patients with DMLC and its clinical problems are discussed in relation to our experience in this case.     

Severe obliterative bronchitis associated with Stevens-Johnson syndrome

We report a case of Stevens-Johnson syndrome (SJS) in which the patient had been diagnosed with severe obliterative bronchitis. A 29-year-old woman was admitted with a high fever and a widespread vesicular rash. She was diagnosed with SJS and betamethasone administration was started. After one month, her vesicular skin rash improved; however, she developed respiratory failure and was assisted with mechanical ventilation. Computed tomography of the chest demonstrated a hyperlucent lung with narrowing of the peripheral vessels. Bronchoscopy revealed an occlusion of the bronchus when the patient exhaled. The flow-volume curve revealed a severe obstructive pattern. The patient was diagnosed with obliterative bronchitis following SJS. She was treated with a bronchodilator and steroids, but could not breathe adequately without the ventilator. During the following year, her PaCO(2) increased to 100 torr and her heart function also continued to worsen. Despite intensive treatment, she died one year and seven months after the onset of SJS. In SJS and toxic epidermal necrolysis (TEN) patients, chronic pulmonary complications are rare, but there is no effective therapy for obliterative bronchitis following SJS/TEN. Therefore, early awareness of this condition is needed and lung transplantation must be considered at an early stage of this disease.     

Primary ciliary dyskinesia treated with living-donor lobar lung transplantation]

We report a case of primary ciliary dyskinesia in which a living-donor lobar lung transplant was performed. A 24-year-old woman with a diagnosis of primary ciliary dyskinesia and bronchiectasis was admitted to Shinshu University Hospital because of persistent dyspnea and pyrexia over a period of 4 months. Although she was given various antibiotics, neutrophilia, elevated plasma C-reactive protein (CRP) levels, and respiratory failure persisted. Chest roentgenograms and computed tomography disclosed severe bronchiectasis and diffuse infiltrative shadows in both lung fields. Pseudomonas aeruginosa was detected in a sputum culture. Although a variety of conventional therapies were administered, the patient's oxygenation progressively deteriorated. She was intubated and assisted by mechanical ventilation. The patient and her family proposed lung transplantation, and we concluded that a living-donor lobar lung transplant would be a suitable treatment for her disease. We transported the patient to Okayama University Hospital by helicopter 10 days after intubation. A living-donor lobar lung transplant was successfully performed with lung tissues donated by the patient's mother and sister for each transplant site.     

Case of pulmonary multi-drug resistant tuberculosis with left destroyed lung, treated with pneumonectomy

A 31-year-old woman complained of cough and fever for 2 months. She was admitted to a hospital and was diagnosed as pulmonary tuberculosis. She received combination therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide. As the drug susceptibility test revealed that the isolated strain was multi-drug resistant, the regimen was changed to pyrazinamide, ethionamide, cycloserine, enviomycin, and levofloxacin. The chemotherapy was not effective, so she received pneumonectomy for left destroyed lung. After surgical treatment, her sputa converted to negative for tubercle bacilli. Surgical treatment such as pneumonectomy is considered to be useful in a case of multi-drug resistant pulmonary tuberculosis.     

A case of group G Streptococcus sepsis, chest wall abscess, and vertebral osteomyelitis mimicking a primary lung cancer with bone metastasis]

A 73-year-old woman who had been followed in our department of gynecology because of ovarian cancer since 2002, was admitted with liver dysfunction and complaining of back pain and light precordial chest pain. The chest radiograph on admission revealed a tumor in her left upper lung field, and chest CT revealed a tumor adjacent to the chest wall and mediastinum. FDG-positron emission tomography (PET) showed abnormal uptake in the tumor and Th6/7, and the subaortic lymph nodes. On the basis of these findings, primary lung cancer with bone metastasis was suspected. She had a high grade fever on admission, and blood cultures were positive for group G streptococcus. The treatment with intravenous penicillin was started. Percutaneous biopsy of the tumor in her left chest showed an abscess wall in the chest wall, but no evidence of malignancy. Transbronchial lung biopsy and CT-guided biopsy also showed no malignant cells. Since the tumor decreased in size and back pain improved gradually by only antibiotic treatment, a diagnosis of sepsis of group G streptococcus, chest wall abscess, and vertebral osteomyelitis was made. She was treated with intravenous penicillin for 4 weeks and oral amoxicillin for another 4 weeks. After 60 days of antibiotic treatment, the tumor vanished.     

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.     

Oxaliplatin (Eloxatin) plus irinotecan combination chemotherapy found effective in refractory metastatic insular thyroid carcinoma.

Therapeutic options for metastatic insular thyroid carcinoma (ITC) are very limited. We present the case of a 39-year-old woman with refractory metastatic ITC who responded to oxaliplatin plus irinotecan chemotherapy. She was initially diagnosed with a locally advanced and metastatic to lung ITC and underwent near-total thyroidectomy. After surgery she was treated and failed to respond first to radioiodine and subsequently to liposomal doxorubicin plus paclitaxel combination chemotherapy and was offered palliative external irradiation for metastases to bone and the brain. Eleven months postdiagnosis the patient became severely dyspnoic as a result of progression of lung metastases and elected to be treated with oxaliplatin plus irinotecan as a secondline chemotherapy. She experienced relief of her dyspnea shortly after treatment initiation and an objective response of her lung metastases was documented after the third course of treatment. Treatment continued for six cycles and tumor remission lasted for 5 months. Toxicity was mild. Confirmatory testing of oxaliplatin-irinotecan combination in case series or single cases of metastatic ITC is warranted.     

Pulmonary tuberculosis with cerebellar lesion in a patient after anti-TNF-alpha (infliximab) treatment for rheumatoid arthritis]

We report a case of pulmonary tuberculosis in a 51-year-old Japanese woman, who received treatment with infliximab for active rheumatoid arthritis. She had cough and sputum after the second infusion of the drug, small nodular lesions of right lung field and left lower lobe on her chest CT and a small nodular lesion of right cerebellar lobe on her cranial MRI were identified. Mycobacterium tuberculosis was cultured from her sputum. Therefore, we diagnosed her illness as pulmonary tuberculosis with a cerebellar lesion. The patient was treated with anti-tuberculosis drugs and showed marked improvement in lesions of the lung and brain. We considered this case a tuberculosis reactivation after infliximab treatment because of the short interval between the administration of infliximab and the occurrence of tuberculosis, and the complication of extrapulmonary lesion that suggested brain tuberculoma.     

Wegener's granulomatosis with eosinophilia

Wegener's granulomatosis with eosinophilia both in blood and tissue samples has been rarely reported. A 25-year-old woman developed fever, granulomatous inflammation of nasal mucosa, pulmonary hemorrhage, suprascleritis, and cutaneous vasculitis. She showed eosinophilia in blood and biospy samples of skin, nasal mucosa, and lung. She was positive for proteinase 3-antineutrophil cytoplasmic antibody. She had no history of asthma. We diagnosed her as Wegener's granulomatosis with eosinophilia rather than Churg-Strauss syndrome. Her mucocutaneous and pulmonary lesions were successfully treated with high-dose corticosteroid and methotrexate, but her suprascleritis required pulsed cyclophosphamide.     

Brain metastasis from follicular thyroid carcinoma: treatment with sorafenib

Background: Sorafenib has shown promise in the treatment of patients with advanced or metastatic thyroid carcinoma. However, its therapeutic effect has not been assessed in patients with brain metastases from follicular thyroid carcinoma (FTC). Here, we report a patient in whom this treatment was employed with a relatively favorable response. Patient and Methods: A 56-year-old woman had a thyroidectomy 8 years previously for FTC. She subsequently developed lung metastases, for which she received seven courses of radioiodine ((131)I) therapy. She developed right hemiplegia and other symptoms and was found to have a ～5-cm lesion in the left parietal lobe. Radiosurgery with a total dose of 28?Gy (7?Gy/day, for 4 days) to treat her brain metastatic lesion was ineffective, and she was referred to us. We treated her with sorafenib, 200?mg orally, on a twice-daily basis. The effect of this intervention was assessed clinically and radiographically using Response Evaluation Criteria in Solid Tumors (RECIST). Summary: Symptoms and signs improved dramatically and continuously after initiation of sorafenib treatment. Partial response (PR) in the brain metastasis and stable disease (SD) in lung metastatic lesions were verified by consecutive imaging findings for more than one year. Despite alopecia, other treatment-related adverse events did not occur. Conclusions: Targeted therapy such as with sorafenib could be an effective alternative therapeutic strategy in the treatment of progressive brain metastasis from differentiated thyroid carcinoma (DTC) when surgery, external beam radiation, and (131)I are not suitable or give poor outcomes. A paradigm of sustained low dose of sorafenib (200?mg,twice a day) may be well-tolerated without compromising maintenance of the therapeutic effect.     

An elderly fludrocortison-responsive woman with hyponatoremia

An 89-years-old woman had anorexia for at least 1 month, and had been given symptomatic treatment at a nearby hospital. She was admitted to our hospital on August 22, 2003, for thorough examination and appropriate treatment for lack of spontaneity and appetite loss. On admission, laboratory data revealed hyponatremia (125 mEq/L) and hypoaldosteronism (0.7 ng/mL). Since hyponatremia did not improve by intravenous drip with saline, we identified the major cause of her complaint as hypoaldosteronism. She was treated with fludrocortisone (0.05 mg/day) and her condition improved immediately. Although she was discharged at that time, her condition shortly deteriorated. She was referred to our hospital on February 10, 2004 for medical treatment. On admission, inadequate oral intake, lack of spontaneity and weakness in her lower legs were noted. The plasma Na concentration was 127 mEq/L. Nasogastric tube feeding was started to prevent aspiration pneumonia because of her dysphagia. Fludrocortisone was given (0.2 mg/day), and she was able to swallow food without nasal feeding tube during the second month of therapy. Laboratory data including plasma natrium concentration were normal. Also she could perform bed-to-wheelchair transfer independently. This is a rare case of a critically ill elderly patient with hyponatremia caused by hypoaldosteronism possibly due to mineral corticoid-responsive hyponatremia of the elderly.     

A case of pulmonary Mycobacterium gordonae infection with pleural effusion]

A 65-year-old woman, treated with prednisolone (5 mg daily) for rheumatoid arthritis, visited our hospital because of right chest pain. Chest CT showed small nodular shadows in the right lung accompanied with right pleural effusion. A pulmonary Mycobacterium gordonae infection was diagnosed, since M. gordonae was identified twice from her sputum. She was treated with rifampicin, ethambutol and streptomycin for two months, and then streptomycin was replaced with clarithromycin. Three months after the initial treatment, M. gordonae was eradicated from her sputum. Pleural puncture revealed bloody, exudative, lymphocytotic pleural effusion, but no malignant cells were identified. Although pathological diagnosis by thoracoscopic pleural biopsy could not be performed, it is likely that the pleural effusion was associated with the pulmonary M. gordonae infection in the present case.