Evaluation of topotecan monotherapy for relapsed small-cell lung cancer after amrubicin monotherapy failure.

Objective: The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy. Patients and Methods: We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital. Results: The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18-51), and 112 days (95% CI = 55-267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections. Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.

Treatment of Cryptococcus gattii Infection Using Voriconazole.

We previously reported a 39-year-old man who presented with pulmonary and cerebral Cryptococcus gattii (genotype VGIIa) infection and was successfully treated with liposomal amphotericin B and flucytosine induction therapy. Following induction therapy, oral fluconazole treatment was initiated as consolidation therapy. However, the patient complained of progressively worsening headache, presenting an elevated cerebrospinal fluid (CSF) cell count. The minimum inhibitory concentrations of the CSF isolate were 8 and 0.12 µg/mL for fluconazole and voriconazole, respectively. The oral administration of voriconazole for more than 18 months alleviated his symptoms. Voriconazole might be useful for controlling refractory cases of C. gattii infection.

Nab-paclitaxel Monotherapy for Relapsed Small Cell Lung Cancer: Retrospective Analysis and Review.

BACKGROUND/AIM: The utility of nanoparticle albumin-bound paclitaxel (nab-PTX) monotherapy in patients with relapsed small-cell lung cancer (SCLC) has not been fully evaluated. We aimed to investigate the efficacy and safety of nab-PTX monotherapy in relapsed SCLC patients, including heavily treated patients. PATIENTS AND METHODS: We retrospectively analysed data from 17 patients with relapsed SCLC who were treated with weekly nab-PTX monotherapy at our hospital. We also reviewed past studies on nab-PTX monotherapy for relapsed SCLC. RESULTS: The response rate, progression-free survival, and overall survival were 29.4%, 48 days (95%CI=33-89), and 134 days (95%CI=64-223), respectively. The most common adverse event of grade ≥3 was leukopenia (17.6%), followed by neutropenia, neuropathy, fatigue, and infections. Our results were consistent with previous studies. CONCLUSION: The efficacy of nab-PTX monotherapy for heavily treated relapsed SCLC patients might be moderate. Further studies to improve outcomes are warranted.

Immunonutritional status and pulmonary cavitation in patients with tuberculosis: A revisit with an assessment of neutrophil/lymphocyte ratio.

BACKGROUND: Several reports have described the importance of immunological and nutritional factors in the morbidity and/or mortality of patients with tuberculosis. The aim of this study was to evaluate the association between pulmonary cavitation and immunonutritional status, assessed by parameters such as neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI), in patients with pulmonary tuberculosis. METHODS: We retrospectively analyzed the data of 137 patients with culture-positive active pulmonary tuberculosis without bacterial pneumonia diagnosed at Kainan Hospital between April 2008 and March 2016. The associations between the levels of serum albumin, lymphocytes, NLR, PNI, platelet to lymphocyte ratio (PLR), and body mass index (BMI) and pulmonary cavitation were evaluated in the patients. RESULTS: A total of 83 men and 63 women (median age, 75 years; range, 16-94 years) were included in the study. Sixty-six patients had smoking history; 55 patients had respiratory symptoms, while 44 patients did not have any symptoms. Patient׳s delay, defined as medical examination performed over 60 days after the onset of symptoms was observed in 25 patients. Univariate analysis showed that high NLR (≥ 5), high PLR (≥200), low serum albumin (<3 g/dL), high neutrophil count (≥6000/mm3), and low lymphocyte count (<1000/mm3) were associated with pulmonary cavitation. Multivariate analysis showed that high NLR and low serum albumin were associated with pulmonary cavitation. CONCLUSION: Malnutrition and increased severity of inflammation may be associated with pulmonary cavitation in patients with tuberculosis. Further studies are warranted to confirm the findings of the present study.

[Osimertinib for an Elderly Patient with Adenocarcinoma of the Lung Harboring EGFR T790M Mutation Diagnosed Using a Pleural Fluid Cell Block].

A 90-year-old woman was referred to our hospital because of dyspnea with pleural effusion that was detected using a chest X-ray. Pleural fluid cell block specimens from the left pleural effusion were shown to be an adenocarcinoma harboring an epidermal growth factor receptor(EGFR)gene mutation(L858R). Erlotinib was administered and the patient responded to treatment for 15 months. Subsequent re-accumulation of the left pleural effusion was detected, and re-evaluation using cell block specimens revealed EGFR T790M mutation positivity. Osimertinib was initiated and the patient responded to treatment for 11 months. Re-evaluation of the left pleural effusion upon failure of osimertinib treatment revealed EGFR T790M mutation negativity. Hence this report summarizes the case of osimertinib therapy being administered to a 90-year-old patient who had EGFR T790M mutation positivity based on a pleural fluid cell block.

Pneumocystis Pneumonia Secondary to Idiopathic CD4+ T-lymphocytopenia: A Comparison of AIDS and Non-AIDS Patients.

A 67-year-old man was admitted to our hospital complaining of dry cough. Chest computed tomography showed diffuse infiltrates and ground-glass opacities in the bilateral lung fields. Transbronchial lung biopsy specimens showed alveoli filled with yeast-like fungi. With a diagnosis of pneumocystis pneumonia (PCP), he was given oral sulfamethoxazole/trimethoprim, to which he responded well. However, seven months later, PCP relapsed. Analyses revealed a low bronchoalveolar lavage fluid CD4/CD8 ratio of 0.04 and CD4+ lymphocytopenia (250/µL). Despite intensive work-up, we were unable to detect the underlying cause of CD4+ lymphocytopenia; therefore, a final diagnosis of idiopathic CD4+ T-lymphocytopenia was made.

A case of wild-type transthyretin amyloidosis associated with organizing pneumonia.

An 81-year-old man was referred to our hospital with bilateral multiple patchy opacities on chest radiography. His chief complaints were a few months' history of intermittent mild cough and slightly yellow sputum. Chest computed tomography (CT) showed non-segmental air-space consolidations with ground-glass opacities. Amyloid deposition with organizing pneumonia (OP) was seen in transbronchial lung biopsy (TBLB) specimens from the left S8. Three months later, the infiltration originally seen in the left lower lobe was remarkably diminished, and new infiltrations in the lingual and right lower lobes were detected on chest CT. Amyloid deposition with OP was seen in TBLB specimens from the left S4. Transthyretin was detected following immunohistochemical examination. The presence of wild-type transthyretin (ATTRwt) was proven using genetic analysis. The present report describes a rare case of ATTRwt amyloidosis associated with OP.

Immunological Status May Predict Response to Nivolumab in Non-small Cell Lung Cancer without Driver Mutations.

BACKGROUND/AIM: It remains challenging to select patients with non-small cell carcinoma (NSCLC) for nivolumab monotherapy. We evaluated whether early termination of nivolumab monotherapy correlated with pretreatment neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI). PATIENTS AND METHODS: Twenty patients received nivolumab monotherapy for NSCLC with wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) during 2016. Early termination and continued therapy were defined as ≤5 and ≥6 cycles of monotherapy, respectively. RESULTS: Early termination and continued therapy groups included 9 and 11 patients, respectively. High pretreatment NLR and low pretreatment PNI were significantly associated with early termination of nivolumab, both in an overall analysis (p<0.001 and p=0.016) and in subgroup analyses of patients with performance scores of 0-1 and ≥30 days of pretreatment drug holidays. CONCLUSION: High NLR and low PNI were associated with early termination of nivolumab monotherapy, suggesting they might be useful biomarkers for treatment selection.

CYFRA 21-1 as a Predictive Marker for Non-small Cell Lung Cancer Treated with Pemetrexed-based Chemotherapy.

BACKGROUND: Pretreatment serum tumor marker levels predict outcome in non-small cell lung cancer (NSCLC). However, little is known about the clinical value of such measurements for patients treated with pemetrexed plus a platinum-derivative. PATIENTS AND METHODS: We retrospectively screened 100 chemotherapy-naïve patients with advanced non-squamous NSCLC treated with pemetrexed plus a platinum-derivative in relation to the pretreatment level of cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA). RESULTS: Sixty one patients with a high CYFRA 21-1 level had statistically shorter progression-free and overall survival than 39 patients with a normal CYFRA 21-1 level (median progression-free survival=127 days vs. 191 days, respectively; p=0.046; median overall survival=360 days vs. 781 days, respectively, p<0.001). Serum CEA level was not related to survival. CONCLUSION: Serum CYFRA 21-1 level is a predictive and prognostic marker in patients with NSCLC treated with pemetrexed plus a platinum-derivative.

Diagnostic delay of pulmonary tuberculosis in patients with acute respiratory distress syndrome associated with aspiration pneumonia: Two case reports and a mini-review from Japan.

Diagnosing active tuberculosis in elderly patients presents problems due to nonspecific symptoms and complications such as aspiration pneumonia. The current study presents two cases of pulmonary tuberculosis with bilateral pulmonary infiltrates associated with aspiration pneumonia. The two elderly patients developed acute respiratory distress syndrome as a result of aspiration pneumonia. The diagnoses of pulmonary tuberculosis were delayed in both cases, as the patients were diagnosed with active tuberculosis following discharge from hospital. The sputum test for acid-fast bacillus at the time of administration was smear-negative/culture-positive in these patients. They were treated with isoniazid, rifampicin and ethambutol, and nosocomial transmission of tuberculosis from these patients was not reported. The number of elderly patients with aspiration pneumonia is predicted to increase rapidly, and aspiration pneumonia combined with pulmonary tuberculosis is a major medical and healthcare concern in Japan. The present study concludes that physicians should always consider the complication of pulmonary tuberculosis when treating pneumonia patients, in particular in treating elderly patients with pulmonary infiltrates.

[CLINICAL INVESTIGATION OF TUBERCULOSIS PATIENTS IN A GENERAL HOSPITAL LACKING A TUBERCULOSIS WARD IN WESTERN AICHI PREFECTURE.]

With the recent decrease in the number of tuberculosis wards and increase in elderly tuber- culosis patients with comorbidities, the role of regional refer- ral hospitals has become more important in tuberculosis management. [Objective]. This study aimed to assess the current state of tuberculosis management and related issues in a general hospital lacking a tuberculosis ward. [Methods] We retrospectively evaluated the clinical char- acteristics and course of patients diagnosed with tuberculosis by culture testing from April 2008 to March 2015 at Kainan Hospital. [Results] A total of 146 patients (83 males and 63 females; mean age 76, range 18-94 years) were diagnosed with active tuberculosis. Of these, 129 were diagnosed with pulmonary tuberculosis (23 had pulmonary tuberculosis with pleurisy), and 17 patients were diagnosed with extrapulmonary tuber- culosis. The chief complains were cough/sputum in 40 cases, fever in 24, and no symptoms in 36. Associated major comorbidities included diabetes mellitus, chronic kidney disease, and malignancy. In 33 patients, over 30 days were required to diagnose tuberculosis after initial evaluation. Drug-resistant strains were detected in 14 patients. 57 were diagnosed with smear-positive pulmonary tuberculosis, and 66 were transferred to a tuberculosis hospital. Modify in anti- tuberculosis therapy due to adverse reactions were reported in 27 patients. [Conclusion] This study evaluated the current state of tuberculosis management in our hospital. Further educational guidance regarding tuberculosis is needed for the hospital staff, and is important for improvement of tuberculosis management in our hospital.

[DISSEMINATED MYCOBACTERIUM INTRACELLULARE INFECTION IN A PATIENT WITH MYELODYSPLASTIC SYNDROME].

A 71-year-old man with myelodysplastic syndrome (MDS) was admitted to our hospital because of recurrent high-grade fever. He was examined for bacterial and fungal infections and treated with antibiotics and antifungal agents. However, he did not achieve a definitive diagnosis and had no apparent improvement for more than a month. Bone marrow aspiration revealed transformation of MDS to acute myeloid leukemia and hemophagocytosis. In addition, Mycobacterium intracellulare was isolated from both a bone marrow specimen and a blood sample. Therefore, he was diagnosed with disseminated Mycobacterium avium complex (MAC) infection with hemophagocytosis. An antibody test was negative for human immunodeficiency virus (HIV). His general condition improved with anti-mycobacterial drug and steroid treatments. Clinicians should suspect disseminated nontuberculous mycobacterial infections in unexplained febrile patients with hematological disorders.

Epidermal growth factor receptor-tyrosine kinase inhibitors for non-small-cell lung cancer patients aged 80 years or older: A retrospective analysis.

The efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in elderly patients with non-small-cell lung cancer (NSCLC) remains uncertain. This retrospective study aimed to evaluate the efficacy and feasibility of EGFR-TKIs for NSCLC patients aged ≥ 80 years. We analyzed data from 21 NSCLC patients aged ≥ 80 years who were administered gefitinib and/or erlotinib between January, 2009 and December, 2014. The clinical characteristics, smoking status, type of EFGR mutation and the efficacy and toxicity of EGFR-TKIs were evaluated in these patients. In total, 14 (66.7%), 5 (23.8%) and 2 patients (9.5%) displayed partial response, stable disease and progressive disease, respectively. The median progression-free survival was 182 days, whereas the median overall survival was 371 days. Adverse events ≥ grade 2 were as follows: skin toxicities, 12 patients; liver function test abnormalities, 7 patients; anorexia, 3 patients; and diarrhea, 2 patients. Dose reduction of EGFR-TKIs due to adverse events was required in 15 patients (71.4%). Although gefitinib and erlotinib therapy may be beneficial in patients aged ≥ 80 years, EGFR-TKI dose modification may be necessary according to the overall medical condition of elderly patients. Further studies are required to evaluate our findings.

[A case of multiple myeloma in a young adult, discovered on the basis of an abnormal finding on a chest X-ray film].

A 35-year-old woman was referred to our hospital because of an abnormal finding on a chest X-ray film. Chest and abdominal computed tomography (CT) revealed a 25 × 5-mm tumor in the anterior right third rib as well as punched-out lesions in the vertebral bodies and iliac bones. Positron emission tomography (PET)/CT revealed accumulation in the right third rib and lumbar vertebral bodies. From these imaging findings and the lumbar magnetic resonance imaging (MRI) findings, we suspected a case of multiple myeloma. We performed histological bone marrow examination, serum protein electrophoresis, and urine immunoelectrophoresis. The patient was finally diagnosed with a Bence-Jones-type multiple myeloma. To our knowledge, this is a rare case of multiple myeloma in a young adult, discovered on the basis of an abnormal finding on a chest X-ray film.

[A case of delayed facial palsy following gamma knife radiosurgery for intractable trigeminal neuralgia].

A 77-year-old woman with hypertension and senile depression had suffered from medically unresponsive trigeminal (left ophthalmic) neuralgia despite microvascular decompression surgery for twice. The patient underwent stereotactic gamma knife radiosurgery (77 Gy) for the neuralgia, resulting in pain relief. However, approximately 20 months after the radiosurgery, she developed left facial palsy with hydrodipsia, left xerophthalmia, and left facial hypesthesia. Oral prednisolone was administered, and these symptoms disappeared in several months. This is the first report of facial palsy following gamma knife radiosurgery for trigeminal neuralgia.